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A new association between CDK5RAP2 microcephaly and congenital cataracts
Author(s) -
Alfares Ahmed,
Alhufayti Ibtihal,
Alsubaie Lamia,
Alowain Mohammed,
Almass Rawan,
Alfadhel Majid,
Kaya Namik,
Eyaid Wafaa
Publication year - 2018
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12232
Subject(s) - microcephaly , genetics , exome sequencing , sanger sequencing , biology , cataracts , compound heterozygosity , phenotype , mutation , gene
Primary microcephaly type 3 is a genetically heterogeneous condition caused by a homozygous or compound heterozygous mutation in CDK5 regulatory subunit associated protein 2 (CDK5RAP2) and characterized by reduced head circumference (<5th percentile) with additional phenotypes varying from pigmentary abnormalities to sensorineural hearing loss. Until now, congenital cataracts have not been reported in patients with primary microcephaly type 3. Clinical report We report multiple affected family members from a consanguineous Saudi family with microcephaly and congenital cataracts. We utilized a next‐generation sequencing–based microcephaly gene panel that revealed a CDK5RAP2 variant (c.4055A>G; p.Glu1352Gly) as the most plausible candidate for the likely etiology in this family. Then we performed family segregation analysis using Sanger sequencing, autozygosity mapping, and whole exome sequencing, all of which revealed no other possible disease‐causing variants. Conclusion Here we report on a new clinical manifestation of CDK5RAP2 and expand the phenotype of primary microcephaly type 3.