In:
American Journal of Medical Genetics Part A, Wiley, Vol. 188, No. 1 ( 2022-01), p. 292-297
Abstract:
Cohen–Gibson syndrome is a rare genetic disorder, characterized by fetal or early childhood overgrowth and mild to severe intellectual disability. It is caused by heterozygous aberrations in EED , which encodes an evolutionary conserved polycomb group (PcG) protein that forms the polycomb repressive complex‐2 (PRC2) together with EZH2, SUZ12, and RBBP7/4. In total, 11 affected individuals with heterozygous pathogenic variants in EED were reported, so far. All variants affect a few key residues within the EED WD40 repeat domain. By trio exome sequencing, we identified the heterozygous missense variant c.581A 〉 G, p.(Asn194Ser) in exon 6 of the EED ‐gene in an individual with moderate intellectual disability, overgrowth, and epilepsy. The same pathogenic variant was detected in 2 of the 11 previously reported cases. Epilepsy, however, was only diagnosed in one other individual with Cohen–Gibson syndrome before. Our findings further confirm that the WD40 repeat domain represents a mutational hotspot; they also expand the clinical spectrum of Cohen–Gibson syndrome and highlight the clinical variability even in individuals with the same pathogenic variant. Furthermore, they indicate a possible association between Cohen–Gibson syndrome and epilepsy.
Type of Medium:
Online Resource
ISSN:
1552-4825
,
1552-4833
DOI:
10.1002/ajmg.a.v188.1
DOI:
10.1002/ajmg.a.62496
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
1493479-6
SSG:
12
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