| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Prepair 1000+ v1.5 | ADPRHL2 |
Zornitza Stark changed review comment from: 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.; to: 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. To be upgraded to GREEN in next version of panel. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | IDUA | Seb Lunke Added phenotypes Mucopolysaccharidosis Ih, 607014 (3) for gene: IDUA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.181 | IGHM | Zornitza Stark changed review comment from: Workaround in place to detect variants in this gene.; to: Workaround possible to detect variants in this gene. However, residual risk of false negative results. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.85 | TFR2 |
Crystle Lee gene: TFR2 was added gene: TFR2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: TFR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TFR2 were set to 29743178 Phenotypes for gene: TFR2 were set to Hemochromatosis, type 3, MIM#604250 Review for gene: TFR2 was set to AMBER Added comment: Age of onset in individuals with TFR2-HHC is earlier than in individuals with HFE-associated hereditary hemochromatosis (Gene Reviews) PMID: 29743178: Mean age at diagnosis for TFR2 HH (32 years) was significantly higher than for HJV HH Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.85 | TECPR2 |
Crystle Lee gene: TECPR2 was added gene: TECPR2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: TECPR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TECPR2 were set to 23176824; 26542466; 35130874 Phenotypes for gene: TECPR2 were set to Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, MIM#615031 Review for gene: TECPR2 was set to GREEN Added comment: SPG49 is an autosomal recessive complicated form of spastic paraplegia. PMID 23176824 reported 4 Jewish Bukharian individuals homozygous for same founder variant and delayed psychomotor development, intellectual disability, and onset of spastic paraplegia in the first decade. Affected individuals also had dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, some of which were fatal. Three additional patients from unrelated non-Bukharian families reported in PMID 26542466, harboring two novel variants (c.1319delT, c.C566T) in this gene. In addition to intellectual disability and evolving spasticity, autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events were prominent Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.85 | TAT |
Crystle Lee gene: TAT was added gene: TAT was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: TAT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TAT were set to 16574453 Phenotypes for gene: TAT were set to Tyrosinemia, type II (MIM#276600) Review for gene: TAT was set to AMBER Added comment: Well established gene-disease association. Also known as Richner-Hanhart syndrome, the clinical hallmarks consist of a triad of painful palmoplantar keratoderma, keratitis with photophobia and variable mental impairment. RHS shows inter and intrafamilial phenotypic variability. Phenotype variability observed even among individuals sharing the same pathogenic variant. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.85 | SLC12A3 |
Crystle Lee gene: SLC12A3 was added gene: SLC12A3 was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: SLC12A3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC12A3 were set to 8528245; 11102542 Phenotypes for gene: SLC12A3 were set to Gitelman syndrome (MIM#263800) Review for gene: SLC12A3 was set to AMBER Added comment: Gitelman syndrome is an autosomal recessive renal tubular salt-wasting disorder characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. It is the most common renal tubular disorder among Caucasians (prevalence of 1 in 40,000). Most individuals have onset of symptoms as adults, but some can present in childhood. Clinical features include transient periods of muscle weakness and tetany, abdominal pains, and chondrocalcinosis. Well established gene-disease association. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.85 | PYGM |
Crystle Lee gene: PYGM was added gene: PYGM was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: PYGM was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PYGM were set to McArdle disease (MIM#232600) Review for gene: PYGM was set to AMBER Added comment: Gene-disease association for bi-allelic variants is well established. McCardle disease: glycogen storage disease type V (GSD5), characterized by onset of exercise intolerance and muscle cramps in childhood or adolescence. Transient myoglobinuria may occur after exercise, due to rhabdomyolysis. Severe myoglobinuria may lead to acute renal failure. Patients may report muscle weakness, myalgia, and lack of endurance since childhood or adolescence. Later in adult life, there is persistent and progressive muscle weakness and atrophy with fatty replacement. McArdle disease is a relatively benign disorder, except for possible renal failure as a complication of myoglobinuria Clinical heterogeneity exists; about 10% of all affected individuals have mild manifestations (e.g., fatigue or poor stamina without contractures) and remain virtually asymptomatic during daily activities of living(Gene Reviews) Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.85 | MCCC2 |
Crystle Lee gene: MCCC2 was added gene: MCCC2 was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: MCCC2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MCCC2 were set to 3-Methylcrotonyl-CoA carboxylase 2 deficiency (MIM#210210) Review for gene: MCCC2 was set to RED Added comment: Variants in this gene cause a biochemical defect. Relationship to clinical features is less certain. Variants in this gene have been reported in multiple individuals with ID/regression/neurological phenotypes. However, ascertainment through NBS programs indicates most individuals remain asymptomatic and therefore caution should be applied in interpreting the clinical significance of variants in this gene (though they undoubtedly cause a biochemical phenotype). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.61 | AIRE |
Crystle Lee gene: AIRE was added gene: AIRE was added to Reproductive Carrier Screen_VCGS. Sources: Literature Mode of inheritance for gene: AIRE was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AIRE were set to 35521792; 28323927 Phenotypes for gene: AIRE were set to Autoimmune polyendocrinopathy syndrome , type I, with or without reversible metaphyseal dysplasia (MIM#240300) Review for gene: AIRE was set to AMBER Added comment: Well established gene disease association. Onset in childhood however phenotype can vary even between siblings with the same genotype. Therefore, it may be difficult (?impossible) to predict the severity/age of onset from the genotype Most reported individuals have bi-allelic variants. AD inheritance has been reported in a single family (OMIM) p.G228W has been shown to have a dominant-negative effect by binding to WT AIRE (OMIM) Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.50 | PLG |
Crystle Lee changed review comment from: 2 AR conditions associated with PLG; Type I plasminogen deficiency and type II plasminogen deficiency, also known as 'dysplasminogenemia'. Patients with type II deficiency are usually asymptomatic (OMIM). The most common clinical manifestation is ligneous conjunctivitis. Other neurological manifestations such as hydrocephalus and Dandy Walker malformation can also be present in some patients PMID: 21174000: Phenotype shows inter- and intra- familial variability. Residual PLG activity does not always correlate with clinical severity AR condition can be associated with severe, early onset presentation; to: 2 AR conditions associated with PLG; Type I plasminogen deficiency and type II plasminogen deficiency, also known as 'dysplasminogenemia'. Patients with type II deficiency are usually asymptomatic (OMIM). The most common clinical manifestation is ligneous conjunctivitis. Other neurological manifestations such as hydrocephalus and Dandy Walker malformation can also be present in some patients PMID: 21174000: Phenotype shows inter- and intra- familial variability. Residual PLG activity does not always correlate with clinical severity AR condition can be associated with severe, early onset presentation |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | IDUA |
Zornitza Stark gene: IDUA was added gene: IDUA was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: IDUA was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: IDUA were set to Mucopolysaccharidosis Ih, 607014 (3) |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||