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11 Jul 2022	Mackenzie's Mission_Reproductive Carrier Screening v0.108	ALG2	Crystle Lee changed review comment from: One additional variant reported in association with CDG on top of the previous patients reported with CDG/congenital myasthenia PMID: 33644825: R251L reported in 3 probands from 2 families with CDG (same patients in PMID: 30397276) Association with myasthenia: Two families reported, same, likely founder variant. Association with CDG: one individual with multisystemic disorder with ID, seizures, coloboma of the iris, hypomyelination, hepatomegaly, and coagulation abnormalities reported in PMID 12684507. Fibroblasts showed severely reduced enzymatic activity.; to: One additional variant reported in association with CDG on top of the previously reviewed patients reported with CDG/congenital myasthenia PMID: 33644825: R251L reported in 3 probands from 2 families with CDG (same patients in PMID: 30397276) Association with myasthenia: Two families reported, same, likely founder variant. Association with CDG: one individual with multisystemic disorder with ID, seizures, coloboma of the iris, hypomyelination, hepatomegaly, and coagulation abnormalities reported in PMID 12684507. Fibroblasts showed severely reduced enzymatic activity.
18 Sep 2021	Mackenzie's Mission_Reproductive Carrier Screening v0.103	BCAP31	Zornitza Stark gene: BCAP31 was added gene: BCAP31 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: BCAP31 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: BCAP31 were set to 24011989; 31330203; 33603160 Phenotypes for gene: BCAP31 were set to Deafness, dystonia, and cerebral hypomyelination, MIM# 300475 Review for gene: BCAP31 was set to GREEN Added comment: More than 20 unrelated families reported. Clinical features include severe intellectual disability (ID), dystonia, deafness, and central hypomyelination. Female carriers are mostly asymptomatic but may present with deafness. Sources: Expert Review
16 Apr 2021	Mackenzie's Mission_Reproductive Carrier Screening v0.69	RPL10	Sarah Righetti changed review comment from: 4 reports of RPL10 variants linked to autism. Connection of RPL10 with autism is queried in the literature - PMID: 23871722. Note that there is sufficient evidence for the syndromal form of the condition - Mental retardation, X-linked, syndromic, 35, MIM #300998 (families with 2,3 and 4 affected males, evidence of segregation); to: 4 reports of RPL10 variants linked to autism. Connection of RPL10 with autism is queried in the literature - PMID: 23871722. Note that there is sufficient evidence for the syndromal form of the condition - Mental retardation, X-linked, syndromic, 35, MIM #300998 (families with 2,3 and 4 affected males, evidence of segregation). The syndromal form is rare - a total of 10 males have been reported in the literature (PMID: 29066376). Given the disputed link to autism, and rarity of the syndromal form of the condition, the gene has been excluded from the MM panel.
13 Feb 2021	Mackenzie's Mission_Reproductive Carrier Screening v0.54	ITGA3	Zornitza Stark gene: ITGA3 was added gene: ITGA3 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: ITGA3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ITGA3 were set to 22512483; 25810266; 27717396; 32198874; 26854491 Phenotypes for gene: ITGA3 were set to Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital, MIM# 614748 Review for gene: ITGA3 was set to GREEN Added comment: This is a neonatal multi-organ disorder that includes congenital interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa. The respiratory and renal features predominate, and lung involvement accounts for the commonly lethal course of the disease. More than 5 unrelated families reported. Sources: Expert Review
13 Feb 2021	Mackenzie's Mission_Reproductive Carrier Screening v0.51	ITGA3	Zornitza Stark gene: ITGA3 was added gene: ITGA3 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: ITGA3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ITGA3 were set to 22512483; 25810266; 27717396; 32198874; 26854491 Phenotypes for gene: ITGA3 were set to Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital, MIM# 614748 Review for gene: ITGA3 was set to GREEN Added comment: This is a severe neonatal multi-organ disorder that includes congenital interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa. The respiratory and renal features predominate, and lung involvement accounts for the commonly lethal course of the disease. More than 5 unrelated families reported. Sources: Expert Review
14 Dec 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.50	COG5	Zornitza Stark gene: COG5 was added gene: COG5 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: COG5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COG5 were set to 23228021; 31572517; 32174980 Phenotypes for gene: COG5 were set to Congenital disorder of glycosylation, type IIi, MIM# 613612 Review for gene: COG5 was set to GREEN Added comment: More than 5 unrelated families reported. Intellectual disability is part of the phenotype. Sources: Expert Review
06 Dec 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.49	ADPRHL2	Edwin Kirk changed review comment from: I agree this is a straightforward GREEN for Mackenzie's Mission. Clearly severe enough phenotype and meets evidence criteria. Only two publications (three if you count PMC5589982) but both with multiple families, consistent phenotype. Change of gene symbol important to note from pipeline point of view.; to: I agree this is a straightforward GREEN for Mackenzie's Mission. Clearly severe enough phenotype and meets evidence criteria. Only two publications (three if you count PMC5589982) but both with multiple families, consistent phenotype. Change of gene symbol important to note from pipeline point of view. Note - I don't think I selected a rating when I entered the above, not certain if this matters.
24 Nov 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.49	MOGS	Zornitza Stark gene: MOGS was added gene: MOGS was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: MOGS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MOGS were set to 31925597; 30587846; 33058492 Phenotypes for gene: MOGS were set to Congenital disorder of glycosylation, type IIb, MIM# 606056 Review for gene: MOGS was set to GREEN Added comment: Six unrelated families reported. Common features include: hypotonia, global developmental delay, feeding problems, seizures, movement disorder, hypogammaglobulinaemia, variable problems with cardiac, dysmorpholology overlapping fingers, short palpebral fissures, micrognathia, can have upsweeping hair at front. Sources: Expert Review
14 Nov 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.48	NTNG2	Zornitza Stark gene: NTNG2 was added gene: NTNG2 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: NTNG2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NTNG2 were set to 31668703; 31692205 Phenotypes for gene: NTNG2 were set to Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia, MIM# 618718 Review for gene: NTNG2 was set to GREEN Added comment: Neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia (NEDBASH) is an autosomal recessive disorder characterized by severely impaired intellectual and motor development, axial and peripheral hypotonia usually with inability to walk, and significant behavioral abnormalities consistent with autism spectrum disorder and reminiscent of Rett syndrome, such as poor communication, stereotypic or repetitive behaviours, hand-wringing, bruxism, and sleep disturbances. Other features include poor overall growth, and joint hypermobility. Rare features include seizures, dystonia, spasticity, and nonspecific brain abnormalities. More than 8 families reported. Sources: Expert Review
06 Nov 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.47	COL2A1	Sarah Righetti edited their review of gene: COL2A1: Added comment: Limited evidence for a recessive condition. 8 patients from 5 families, at least 2 mildly affected. Almost all literature dominant. PMID: 31755234 (Girisha et al. 2020) six patients from 4 families, variability in phenotype. PMID: 32896647 (Al-Sannaa et al 2020) two sibs from consang family with disproportionate short stature, ocular abnormalities, cleft palate and hearing impairment. Radiographic study showed signs of a spondyloepiphyseal dysplasia, compatible with a type 2 collagen disorder. Both siblings homozygous for c.3111+2T > C p.(Glu1 033Lysfs *5) splice site variant in the COL2A1 gene. Het parents phenotypically normal. cDNA analysis on skin fibroblasts demonstrated abberant splicing. Created: 6 Nov 2020, 4:59 a.; Changed rating: AMBER
06 Nov 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.47	MBTPS1	Sarah Righetti gene: MBTPS1 was added gene: MBTPS1 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review,Literature Mode of inheritance for gene: MBTPS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MBTPS1 were set to 32857899; 32420688; 30046013 Phenotypes for gene: MBTPS1 were set to ?Spondyloepiphyseal dysplasia, Kondo-Fu type, MIM #618392 Review for gene: MBTPS1 was set to AMBER Added comment: Three unrelated individuals reported with bi-allelic variants in this gene and a skeletal dysplasia, one described with SRS-like features. Elevated blood lysosomal enzymes are also a feature. Sources: Expert Review, Literature
06 Nov 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.47	UPB1	Sarah Righetti changed review comment from: Insufficient evidence that abolition of enzymatic activity is disease-causing. LOF/pathogenic missense alleles at high frequency in general population.In particular, the most frequently reported variant, p.Arg326Gln, is very common among East Asians, with a carrier frequency of 1 in 20 and 1 in 907 being homozygous for the variant. Moreover, published reports (PMID: 24526388) include multiple individuals with mild or no phenotypes. ; to: Insufficient evidence that abolition of enzymatic activity is disease-causing. LOF/pathogenic missense alleles at high frequency in general population.In particular, the most frequently reported variant, p.Arg326Gln, is very common among East Asians, with a carrier frequency of 1 in 20 and 1 in 907 being homozygous for the variant. Moreover, published reports (PMID: 24526388) include multiple individuals with mild or no phenotypes.
06 Nov 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.47	UPB1	Sarah Righetti changed review comment from: Insufficient evidence that abolition of enzymatic activity is disease-causing. LOF/pathogenic missense alleles at high frequency in general population.; to: Insufficient evidence that abolition of enzymatic activity is disease-causing. LOF/pathogenic missense alleles at high frequency in general population.In particular, the most frequently reported variant, p.Arg326Gln, is very common among East Asians, with a carrier frequency of 1 in 20 and 1 in 907 being homozygous for the variant. Moreover, published reports (PMID: 24526388) include multiple individuals with mild or no phenotypes.
29 Oct 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.33	VAC14	Sarah Righetti gene: VAC14 was added gene: VAC14 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: VAC14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VAC14 were set to 27292112; 31392254; 31591492; 31387860; 31876398 Phenotypes for gene: VAC14 were set to Striatonigral degeneration, childhood-onset, MIM#617054 Review for gene: VAC14 was set to GREEN Added comment: Multiple reports in unrelated patients Sources: Expert Review
29 Oct 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.32	PRKRA	Sarah Righetti gene: PRKRA was added gene: PRKRA was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: PRKRA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRKRA were set to 29279192; 25142429 Phenotypes for gene: PRKRA were set to Dystonia 16, MIM#612067 Review for gene: PRKRA was set to GREEN Added comment: Sufficient reports - most common variant is c.665C>T p.Pro222Leu, rs121434410 PMID 29279192 (2017)- 7 patients in Brazilian cohort - most homozygous for P222L PMID 2514249: (2014) - 2 Polish sibs - hom for P222L Sources: Expert Review
29 Oct 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.32	IL10RB	Sarah Righetti changed review comment from: Sufficient patients reported (note protein encoded by IL10RB is IL10R2) 19890111: 2 affected sibs with hom stop-gain. 22549091: 8 patients - although a couple where the pathogenicity is in doubt, sufficient overall evidence. Note patient 1 and patient 2 (siblings sharing the same homozygous mutation) had different disease severity) - likely to be other factors which contribute to phenotype. Severe phenotype.; to: Sufficient patients reported (note protein encoded by IL10RB is IL10R2) 19890111: 2 affected sibs with hom stop-gain. 22549091: 8 patients - although a couple where the pathogenicity is in doubt, sufficient overall evidence. Note patient 1 and patient 2 (siblings sharing the same homozygous mutation) had different disease severity - likely to be other factors which contribute to phenotype. Severe phenotype.
29 Oct 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.32	IL10RB	Sarah Righetti commented on gene: IL10RB: Sufficient patients reported (note protein encoded by IL10RB is IL10R2) 19890111: 2 affected sibs with hom stop-gain. 22549091: 8 patients - although a couple where the pathogenicity is in doubt, sufficient overall evidence. Note patient 1 and patient 2 (siblings sharing the same homozygous mutation) had different disease severity) - likely to be other factors which contribute to phenotype. Severe phenotype.
29 Oct 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.32	PPIB	Sarah Righetti changed review comment from: Sources: Expert Review; to: >10 cases across multiple reports, severe phenotype
16 Oct 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.32	SPEG	Zornitza Stark gene: SPEG was added gene: SPEG was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: SPEG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPEG were set to 25087613; 31625632; 30412272; 30157964; 29614691; 29474540; 28624463; 26578207; 25087613 Phenotypes for gene: SPEG were set to Centronuclear myopathy 5, MIM# 615959 Review for gene: SPEG was set to GREEN Added comment: Centronuclear myopathy-5 is an autosomal recessive congenital myopathy characterized by severe neonatal hypotonia with respiratory insufficiency and difficulty feeding. Some individuals die in infancy, and some develop dilated cardiomyopathy. More than 10 unrelated families reported, functional data. Sources: Expert Review
16 Oct 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.31	KCNE1	Seb Lunke changed review comment from: Comment by Ivan Macciocca: as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group: Genetic evidence associating this gene with disease causality was also based on a candidate gene approach and was limited in scope. There is strong evidence for a role of KCNE1 in acquired LQTS which led the panel to classify it as having limited evidence for disease causality for unprovoked LQTS, although studies in large families with variant segregation is lacking. Furthermore, several case reports have identified homozygous or compound heterozygous rare variants in KCNE1 in patients with Jervell and Lange-Nielsen syndrome; however, parents or siblings carrying only 1 allele have reported normal phenotypes, suggesting an association of this gene with an autosomal-recessive form of LQTS. Comment by Zornitza Stark: Rated as MODERATE by ClinGen for bi-allelic disease. Evidence for mono-allelic disease is limited. Additional: Technically challenging as only coding exon has reduced mappability and putative (but disputed) pseudogene KCNE1B that was introduced in GRCh38, but is not present in GRCh37/hg19 (PMID31527855, PMID30936463); to: Comment by Ivan Macciocca: as reported in Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240, by the International, Multicentered LQTS ClinGen Working Group: Genetic evidence associating this gene with disease causality was also based on a candidate gene approach and was limited in scope. There is strong evidence for a role of KCNE1 in acquired LQTS which led the panel to classify it as having limited evidence for disease causality for unprovoked LQTS, although studies in large families with variant segregation is lacking. Furthermore, several case reports have identified homozygous or compound heterozygous rare variants in KCNE1 in patients with Jervell and Lange-Nielsen syndrome; however, parents or siblings carrying only 1 allele have reported normal phenotypes, suggesting an association of this gene with an autosomal-recessive form of LQTS. Comment by Zornitza Stark: Rated as MODERATE by ClinGen for bi-allelic disease. Evidence for mono-allelic disease is limited. Additional: Technically challenging as only coding exon has reduced mappability and putative (but disputed) pseudogene KCNE1B that was introduced in GRCh38, but is not present in GRCh37/hg19 (PMID31527855, PMID30936463) Association with Long-QT is questionable. Remains GREEN for Deafness, but on balance does not currently meet inclusion criteria for Mackenzie's Mission
16 Oct 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.28	B9D1	Sarah Righetti gene: B9D1 was added gene: B9D1 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Literature Mode of inheritance for gene: B9D1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: B9D1 were set to 24886560; 21493627; 25920555 Phenotypes for gene: B9D1 were set to Meckel syndrome 9, MIM# 614209; Joubert syndrome 27, MIM# 617120 Added comment: PMID: 24886560 - 2 unrelated patients with mild Joubert syndrome (1 hom missense, 1 chet inframe deletion/missense). Authors suggest biallelic null variants are lethal. PMID: 21493627 - 1 fetus with Meckel syndrome and chet for a splice/gene deletion. The splice variant proven to result in exon skipping -> PTC, but the deletion spans a large region including 18 other genes. Patient also had an additional variant in CEP290 called LP. Authors perform functional studies on patient cells but given the large deletion/CEP290 variant, results cannot be used. PMID 25920555 - another report of digenic inheritance - not usable, patient was only heterozygous for a single B9D1 variant Summary: 2 unrelated patients, AMBER Sources: Literature
15 Sep 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.23	ISCA1	Zornitza Stark gene: ISCA1 was added gene: ISCA1 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: ISCA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ISCA1 were set to 28356563; 32092383; 31016283; 30113620; 30105122 Phenotypes for gene: ISCA1 were set to Multiple mitochondrial dysfunctions syndrome 5, MIM# 617613 Review for gene: ISCA1 was set to GREEN Added comment: Multiple unrelated families reported. Severe disorder characterised by progressive neurologic deterioration beginning in early infancy. Affected individuals have essentially no psychomotor development and have early-onset seizures with neurologic decline and spasticity. Brain imaging shows severe leukodystrophy with evidence of dys- or delayed myelination. Rat model results in early lethality. Founder variant c.259G > A, p.(Glu87Lys) reported in Indian families. Sources: Expert Review
12 Sep 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.22	ADPRHL2	Zornitza Stark gene: ADPRHL2 was added gene: ADPRHL2 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review new gene name tags were added to gene: ADPRHL2. Mode of inheritance for gene: ADPRHL2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADPRHL2 were set to 30100084; 30401461 Phenotypes for gene: ADPRHL2 were set to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM#618170 Review for gene: ADPRHL2 was set to GREEN Added comment: Fourteen unrelated families reported with stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS), an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. The disorder is characterised by cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some individuals develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy. New HGNC approved name is ADPRS. Sources: Expert Review
05 Sep 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.20	FITM2	Zornitza Stark gene: FITM2 was added gene: FITM2 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert list Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FITM2 were set to 28067622; 30214770; 30288795 Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635 Review for gene: FITM2 was set to GREEN Added comment: Autosomal recessive condition characterised by global developmental delay, early-onset progressive sensorineural hearing impairment, regression of motor skills, dystonia, poor overall growth, and low body mass index (BMI). More variable features may include ichthyosis-like skin abnormalities or sensory neuropathy. 7 individuals from 3 unrelated families reported, supportive Drosophila model. Sources: Expert list
04 Sep 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.19	YIF1B	Zornitza Stark gene: YIF1B was added gene: YIF1B was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: YIF1B were set to 32006098; 26077767 Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement Review for gene: YIF1B was set to GREEN Added comment: 6 individuals (from 5 families) with biallelic YIF1B truncating variants reported. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder (dystonia/spasticity/dyskinesia). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3. Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*. Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichement in in genes important for nervous system development and function. Sources: Expert Review
04 Sep 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.18	DYNC1I2	Zornitza Stark gene: DYNC1I2 was added gene: DYNC1I2 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: DYNC1I2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DYNC1I2 were set to 31079899 Phenotypes for gene: DYNC1I2 were set to Neurodevelopmental disorder with microcephaly and structural brain anomalies , MIM#618492 Review for gene: DYNC1I2 was set to GREEN Added comment: Five individuals from three unrelated families reported. Sources: Expert Review
04 Sep 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.17	TRAPPC6B	Zornitza Stark gene: TRAPPC6B was added gene: TRAPPC6B was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: TRAPPC6B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRAPPC6B were set to 28626029; 28397838; 31687267 Phenotypes for gene: TRAPPC6B were set to Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy, MIM# 617862 Review for gene: TRAPPC6B was set to GREEN Added comment: Five unrelated families reported with autosomal recessive neurodegenerative disorder characterised by global developmental delay, severe intellectual disability with poor or absent speech and autistic stereotypic behaviors, microcephaly, early-onset generalized seizures, and hypotonia. Sources: Expert Review
04 Sep 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.16	TRAPPC12	Zornitza Stark gene: TRAPPC12 was added gene: TRAPPC12 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: TRAPPC12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRAPPC12 were set to 32369837; 28777934 Phenotypes for gene: TRAPPC12 were set to Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, MIM# 617669 Review for gene: TRAPPC12 was set to GREEN Added comment: Four families reported with a severe progressive encephalopathy characterized by microcephaly, global developmental delay, and hearing loss. Sources: Expert Review
04 Sep 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.15	TPRKB	Zornitza Stark gene: TPRKB was added gene: TPRKB was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: TPRKB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TPRKB were set to 28805828; 30053862 Phenotypes for gene: TPRKB were set to Galloway-Mowat syndrome 5, MIM# 617731 Review for gene: TPRKB was set to GREEN Added comment: Three unrelated families reported with renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly. Sources: Expert Review
04 Sep 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.14	TP53RK	Zornitza Stark gene: TP53RK was added gene: TP53RK was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert Review Mode of inheritance for gene: TP53RK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TP53RK were set to 28805828; 30053862 Phenotypes for gene: TP53RK were set to Galloway-Mowat syndrome 4, MIM# 617730 Review for gene: TP53RK was set to GREEN Added comment: At least 4 unrelated families reported with renal-neurologic disease characterised by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities, and delayed psychomotor development. Most individuals have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable. Sources: Expert Review
04 Sep 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.13	TBC1D20	Zornitza Stark gene: TBC1D20 was added gene: TBC1D20 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert list Mode of inheritance for gene: TBC1D20 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TBC1D20 were set to 24239381; 32740904; 32162791 Phenotypes for gene: TBC1D20 were set to Warburg micro syndrome 4, MIM# 615663; Martsolf syndrome Review for gene: TBC1D20 was set to GREEN Added comment: 7 unrelated families reported with autosomal recessive syndrome characterised by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. One of the families is described as Martsolf syndrome, the rest as Warburg micro. Sources: Expert list
04 Sep 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.12	TMEM94	Zornitza Stark gene: TMEM94 was added gene: TMEM94 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert list Mode of inheritance for gene: TMEM94 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM94 were set to 30526868 Phenotypes for gene: TMEM94 were set to Intellectual developmental disorder with cardiac defects and dysmorphic facies, MIM#618316 Review for gene: TMEM94 was set to GREEN Added comment: 10 individuals from 6 unrelated families reported. Sources: Expert list
03 Sep 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.11	PTPN23	Zornitza Stark gene: PTPN23 was added gene: PTPN23 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Expert list Mode of inheritance for gene: PTPN23 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTPN23 were set to 31395947; 29899372; 29090338; 27848944; 25558065 Phenotypes for gene: PTPN23 were set to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity, MIM# 618890 Review for gene: PTPN23 was set to GREEN Added comment: Over 10 families reported with an autosomal recessive neurologic disorder characterised by global developmental delay apparent from early infancy, poor overall growth often with microcephaly (6/10), impaired intellectual development with delayed or absent speech, axial hypotonia, and peripheral spasticity. Additional common but variable features include early-onset seizures, optic atrophy with poor visual fixation, and dysmorphic facial features. Brain imaging shows cerebral atrophy, poor or absent myelination with loss of white matter volume, and often hypoplasia of the corpus callosum and/or cerebellum. Sources: Expert list
19 Apr 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.0	UROS	Zornitza Stark gene: UROS was added gene: UROS was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: UROS were set to Porphyria, congenital erythropoietic, 263700 (3)
19 Apr 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.0	SLC16A1	Zornitza Stark gene: SLC16A1 was added gene: SLC16A1 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: SLC16A1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC16A1 were set to Monocarboxylate transporter 1 deficiency, 616095 (3)
19 Apr 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.0	POR	Zornitza Stark gene: POR was added gene: POR was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: POR was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: POR were set to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis, 201750 (3)
19 Apr 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.0	LRP5	Zornitza Stark gene: LRP5 was added gene: LRP5 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: LRP5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: LRP5 were set to Osteoporosis-pseudoglioma syndrome, 259770 (3)
19 Apr 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.0	LAMA1	Zornitza Stark gene: LAMA1 was added gene: LAMA1 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: LAMA1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: LAMA1 were set to Poretti-Boltshauser syndrome, 615960 (3)
19 Apr 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.0	FOLR1	Zornitza Stark gene: FOLR1 was added gene: FOLR1 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: FOLR1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FOLR1 were set to Neurodegeneration due to cerebral folate transport deficiency, 613068 (3)
19 Apr 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.0	COL4A5	Zornitza Stark gene: COL4A5 was added gene: COL4A5 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: COL4A5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: COL4A5 were set to Alport syndrome 1, X-linked
19 Apr 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.0	COL4A4	Zornitza Stark gene: COL4A4 was added gene: COL4A4 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: COL4A4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: COL4A4 were set to Alport syndrome, autosomal recessive, 203780 (3)
19 Apr 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.0	COL4A3	Zornitza Stark gene: COL4A3 was added gene: COL4A3 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: COL4A3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: COL4A3 were set to Alport syndrome, autosomal recessive, 203780 (3)
19 Apr 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.0	ALAD	Zornitza Stark gene: ALAD was added gene: ALAD was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: ALAD was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ALAD were set to Porphyria, acute hepatic, 612740 (3)
19 Apr 2020	Mackenzie's Mission_Reproductive Carrier Screening v0.0	ACTA1	Zornitza Stark gene: ACTA1 was added gene: ACTA1 was added to Mackenzie's Mission_Reproductive Carrier Screening. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: ACTA1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ACTA1 were set to Myopathy, congenital, with fiber-type disproportion 1, 255310 (3)