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CRIPT exonic deletion and a novel missense mutation in a female with short stature, dysmorphic features, microcephaly, and pigmentary abnormalities
Author(s) -
Leduc Magalie S.,
Niu Zhiyv,
Bi Weimin,
Zhu Wenmiao,
Miloslavskaya Irene,
Chiang Theodore,
Streff Haley,
Seavitt John R.,
Murray Stephen A.,
Eng Christine,
Chan Audrey,
Yang Yaping,
Lalani Seema R.
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37780
Subject(s) - genetics , missense mutation , exon , microcephaly , biology , proband , exome sequencing , frontal bossing , short stature , mutation , gene , anatomy , endocrinology
Mutations in CRIPT encoding cysteine‐rich PDZ domain‐binding protein are rare, and to date have been reported in only two patients with autosomal recessive primordial dwarfism and distinctive facies. Here, we describe a female with biallelic mutations in CRIPT presenting with postnatal growth retardation, global developmental delay, and dysmorphic features including frontal bossing, high forehead, and sparse hair and eyebrows. Additional clinical features included high myopia, admixed hyper‐ and hypopigmented macules primarily on the face, arms, and legs, and syndactyly of 4–5 toes bilaterally. Using whole exome sequencing (WES) and chromosomal microarray analysis (CMA), we detected a c.8G>A (p.C3Y) missense variant in exon 1 of the CRIPT gene inherited from the mother and a 1,331 bp deletion encompassing exon 1, inherited from the father. The c.8G>A (p.C3Y) missense variant in CRIPT was apparently homozygous in the proband due to the exon 1 deletion. Our findings illustrate the clinical utility of combining WES with copy number variant (CNV) analysis to provide a molecular diagnosis to patients with rare Mendelian disorders. Our findings also illustrate the clinical spectrum of CRIPT related mutations. © 2016 Wiley Periodicals, Inc.