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| Intellectual disability - microarray and sequencing v3.421 | KLF1 |
Arina Puzriakova Source Expert Review Red was added to KLF1. Rating Changed from Amber List (moderate evidence) to Red List (low evidence) |
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| Intellectual disability - microarray and sequencing v3.253 | KLF1 | Arina Puzriakova commented on gene: KLF1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v3.0 | KLF1 | Zornitza Stark reviewed gene: KLF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.588 | ZNF462 |
Konstantinos Varvagiannis gene: ZNF462 was added gene: ZNF462 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: ZNF462 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ZNF462 were set to 28513610; 29427787; 14564155; 12825074 Phenotypes for gene: ZNF462 were set to Ptosis; Prominent metopic ridge; Craniosynostosis; Global developmental delay; Intellectual disability; Autistic behavior Penetrance for gene: ZNF462 were set to unknown Review for gene: ZNF462 was set to AMBER gene: ZNF462 was marked as current diagnostic Added comment: Weiss et al. (PMID: 28513610) report on 8 individuals (from 6 unrelated families) with heterozygous pathogenic variants affecting ZNF462. Frequent features included ptosis metopic ridging, craniosynostosis, dysgenesis of corpus callosum. DD (with or without ASD) was a feature in 4 (4/8), one of whom was reported to present mild ID. 4 LoF mutations as well as 2 9q31.2 deletions spanning also other genes are reported [NM_021224.4]: Fam. 1 - c.3787C>T p.(Arg1263*) (familial) - Normal development in all 3 family members Fam. 2 - c.2979_2980delinsA p.(Val994Trpfs*147) (de novo) - DD Fam. 3 - c.4263delA p.(Glu1422Serfs*6) (de novo) - DD Fam. 4 - Chr9:g.(108940763-110561397)del (hg19) (de novo) - Normal development Fam. 5- Chr9:g(108464368-110362345)del (hg19) (de novo) - DD with mild ID Fam. 6 - c.5145delC p.(Tyr1716Thrfs*28) (de novo) - DD There were no expression/functional studies performed although haploinsufficiency can be presumed based on these variants (ZNF462 has a pLI of 1 in ExAC). ----------- Cosemans et al. (PMID: 29427787) report on an individual investigated - among others - for mild ID and ASD. This individual harbored a de novo (complex) translocation disrupting ZNF462 and KLF12. As this subject presented similar features to those reported by Weiss et al. (eg. craniofacial anomalies, abn. development, ASD) and given that KLF12 is not associated with any disorder, the phenotype of this individual was thought to be secondary to disruption of ZNF462. Details on this patient - before delineation of the translocation breakpoints - were provided previously by Fryns and Hendrickx ( PMID:9297446). ----------- Cited by the previous article, a further case of ZNF462 disruption due to translocation was previously published in the literature (same individual - Talisetti et al. PMID: 14564155 / Ramocki et al. PMID: 12825074). Profound ID was among the features of this individual although the translocation disrupted also a further ID gene (ASXL2). ----------- In ClinVar 8 variants have been submitted as pathogenic/likely pathogenic although a phenotype is provided only for 3 variants published by Weiss et al.(submitting lab participating in PMID: 28513610 / SCV000494060.1 corresp. to Fam.1 / SCV000494061.1 - Fam.2 / SCV000494062.1 - Fam. 3). ----------- Several individuals with de novo coding variants in ZNF462 have been reported in the context of larger cohorts (some with ID as a principal feature). http://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=ZNF462 ----------- In Decipher apart from the DDD study participants DDD4K.03663 and DDD4K.03792 (appearing in the denovo-db) with LoF and abnormality of the nervous system, several further individuals have been submitted. 2 of these subjects, harbored a de novo LoF (submitted as pathogenic) and had ID as a feature. ---------- ZNF462 is included in the DD panel of G2P, associated with Craniofacial anomalies, corpus callosum dysgenesis, ptosis, and developmental delay [Disease confidence: probable / Global DD (but not ID) among the phenotypes assigned to this entry]. This gene is not associated with any phenotype in OMIM. ---------- ZNF462 is included in gene panels for ID offered by diagnostic laboratories (incl. Radboudumc). ---------- As a result this gene can be considered for inclusion in the ID panel probably as amber (or green if the current evidence is thought to be sufficient). Sources: Literature, Radboud University Medical Center, Nijmegen |
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| Intellectual disability - microarray and sequencing | KLF1 | BRIDGE consortium edited their review of KLF1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing | KLF1 | Louise Daugherty classified KLF1 as amber | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing | KLF1 | Louise Daugherty commented on KLF1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing | KLF1 | BRIDGE consortium reviewed KLF1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||