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| Clefting disorders v0.245 | ZRSR2 |
Chris Ciotta gene: ZRSR2 was added gene: ZRSR2 was added to Clefting disorders. Sources: Literature Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: ZRSR2 were set to PMID: 38158857 Phenotypes for gene: ZRSR2 were set to Orofacialdigital syndrome MONDO:0015375, ZRSR2-related Review for gene: ZRSR2 was set to GREEN Added comment: Oral-facial-digital (OFD) syndrome with brain anomalies ranging from alobar holoprosencephaly to pituitary anomalies. Six unrelated families with two truncating variants and functional studies: - p.(Gly404GlufsTer23): detected in one family with 2x affected males - p.(Arg403GlyfsTer24): 5 unrelated families, both de novo and inherited Sources: Literature |
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| Clefting disorders v0.202 | ARID1B |
Zornitza Stark gene: ARID1B was added gene: ARID1B was added to Clefting disorders. Sources: Expert Review Mode of inheritance for gene: ARID1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARID1B were set to 30349098; 37010288 Phenotypes for gene: ARID1B were set to Coffin-Siris syndrome 1, OMIM:135900 Review for gene: ARID1B was set to AMBER Added comment: Although there are more than three unrelated cases with ARID1B monoallelic variants reported with either cleft palate, cleft uvula or bifid uvula, clefting is not consistently present in individuals with ARID1B variants. PMID:30349098 - On this web-based survey based on previously reported features of individuals with variants in ARID1B gene (143 in total), which also included submissions to DECIPHER database, two individuals were identified with cleft palate, one with cleft uvula, two with bifid uvula and three with sub mucous cleft. Although variants identified in these patients are reported in this publication, there is no association of individual patients to phenotypes available. Of >100 patients with ARID1B variants in the DECIPHER database, only one patient (c.3183_3184insT/ p.Tyr1062LeufsTer10) was reported with submucous cleft soft palate and two patients (c.4155_4156insA/ p.Asn1386LysfsTer18 & c.2620+5G>A) were reported with bifid uvula. Sources: Expert Review |
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| Clefting disorders v0.111 | PLCH1 |
Zornitza Stark gene: PLCH1 was added gene: PLCH1 was added to Clefting disorders. Sources: Literature Mode of inheritance for gene: PLCH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLCH1 were set to 33820834 Phenotypes for gene: PLCH1 were set to Holoprosencephaly spectrum; Severe developmental delay; Brain malformations Review for gene: PLCH1 was set to AMBER Added comment: PMID: 33820834 (2021) - Two sibling pairs from two unrelated families with a holoprosencephaly spectrum phenotype and different homozygous PLCH1 variants (c.2065C>T, p.Arg689* and c.4235delA, p.Cys1079ValfsTer16, respectively). One family presented with congenital hydrocephalus, epilepsy, significant developmental delay and a monoventricle or fused thalami; while sibs from the second family had alobar holoprosencephaly and cyclopia. 3/4 individuals also displayed a cleft palate and congenital heart disease. Human embryo immunohistochemistry showed PLCH1 to be expressed in the notorcord, developing spinal cord (in a ventral to dorsal gradient), dorsal root ganglia, cerebellum and dermatomyosome. Sources: Literature |
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| Clefting disorders v0.52 | FST | Zornitza Stark Marked gene: FST as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clefting disorders v0.52 | FST | Zornitza Stark Gene: fst has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clefting disorders v0.44 | FST |
Chirag Patel gene: FST was added gene: FST was added to Clefting_GEL. Sources: Expert list Mode of inheritance for gene: FST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FST were set to PubMed: 31215115 Phenotypes for gene: FST were set to orofacial clefting Review for gene: FST was set to RED Added comment: In a cohort of 72 families with orofacial clefting, Cox et al. (2019) performed exome sequencing and identified a father and 2 daughters (family 22) with cleft lip and palate who were heterozygous for missense variant (C56Y) in FST. A highly conserved residue within the 63-residue N-terminal domain. The variant was not found in the unaffected paternal grandmother or in the gnomAD database. Classed as a VUS. Functional analysis in transfected HEK293T cells, using a stable cell line sensitive to stimulation by the FST downstream target GDF11, demonstrated that wildtype FST efficiently and completely antagonized GDF11-stimulated reporter activity. In contrast, the C56Y mutant did not significantly inhibit the stimulation of reporter activity, regardless of the amount of mutant vector transfected. Sources: Expert list |
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