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| Intellectual disability - microarray and sequencing v3.0 | SUPT16H |
Konstantinos Varvagiannis gene: SUPT16H was added gene: SUPT16H was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: SUPT16H was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SUPT16H were set to http://dx.doi.org/10.1136/jmedgenet-2019-106193 Phenotypes for gene: SUPT16H were set to Global developmental delay; Intellectual disability; Abnormality of the corpus callosum Penetrance for gene: SUPT16H were set to Complete Review for gene: SUPT16H was set to AMBER Added comment: Bina et al (2020 - http://dx.doi.org/10.1136/jmedgenet-2019-106193) report on 4 unrelated individuals with heterozygous SNVs affecting SUPT16H as well as 1 further with microdeletion spanning this gene. The phenotype consisted of DD with subsequent ID in a subset of them (ages of the cohort: 2y-14y), autistic features in few, abnormalities of the corpus callosum (for 3 with available MRI images), variable gastrointestinal problems in some, and possibly minor dysmorphic features. SUPT16H encodes a subunit of the FACT (facilitates chromatin transcription) complex, a chromatin-specific factor required for transcription elongation as well as for DNA replication and repair (OMIM citing Belotserkovskaya et al. 2003 - PMID: 12934006). The 2 subunits of the complex [Spt16 (encoded by SUPT16H) and SSRP1] are essential for histone regulation. As the authors note, Spt16 interacts with the histone dimer H2A-H2B during transcription to allow RNA polymerase access to previously coiled DNA [cited PMIDs : 9489704, 10421373 / A recent study by Liu et al 2019 (PMID: 31775157) appears highly relevant]. SUPT16H has a Z-score of 5.1 in gnomAD and a pLI of 1 (%HI of 22.56 in Decipher). SNVs : 4 de novo missense SNVs were identified following exome sequencing (NM_007192.3:c.484A>G or I162V / L432P / N571S / R734W), all absent from gnomAD and mostly predicted to be deleterious (I162V predicted benign, tolerated, disease-causing by PolyPhen2, SIFT, MutationTaster respectively and had a CADD score of 13.61). Prior work-up for these individuals (incl. CMA in some / MS-MLPA for Angelman s. in 1 / metabolic investigations) had (probably) not revealed an apparent cause, with small CNVs inherited from healthy parents (a 4q13.3 dup / 20q13.2 del - coordinates not provided). There were no studies performed for the identified variants. CNVs : A 5th individual reported by Bina et al was found to harbor a 2.05 Mb 14q11.2 deletion spanning SUPT16H. The specific deletion also spanned CHD8 while the same individual harbored also a 30.17 Mb duplication of 18p11.32q12.1. CNVs spanning SUPT16H reported to date, also span the (very) proximal CHD8. [Genomic coordinates (GRCh38) for SUPT16H and CHD8 as provided by OMIM : 14:21,351,471-21,384,018 / 14:21,385,198-21,456,122]. Haploinsufficiency of CHD8 is associated with a distinctive syndrome with overgrowth and ID (Douzgou et al 2019 - PMID: 31001818). The phenotype of SUPT16H-CHD8 duplications is discussed in other studies/reviews. [Smol et al 2020 - PMID: 31823155 / Smyk et al 2016 - PMID: 26834018]. Animal models were not commented on by Bina et al (possibly not available for mouse : http://www.informatics.jax.org/marker/MGI:1890948 / https://www.mousephenotype.org/data/genes/MGI:1890948 ). Sources: Literature |
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| Intellectual disability - microarray and sequencing v2.851 | CHD8 | Louise Daugherty Phenotypes for gene: CHD8 were changed from AUTISM to Overgrowth with Intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.468 | CHD8 | Louise Daugherty Source Victorian Clinical Genetics Services was added to CHD8. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||