title: CRIPT exonic deletion and a novel missense mutation in a female with short stature, dysmorphic features, microcephaly, and pigmentary abnormalities.
abstract: 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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Magalie S
authors.initials: MS
authors.lastname: Leduc
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Zhiyv
authors.initials: Z
authors.lastname: Niu
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.|Baylor Miraca Genetics Laboratories, Houston, Texas.
authors.forename: Weimin
authors.initials: W
authors.lastname: Bi
authors.affiliation: Baylor Miraca Genetics Laboratories, Houston, Texas.
authors.forename: Wenmiao
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Baylor Miraca Genetics Laboratories, Houston, Texas.
authors.forename: Irene
authors.initials: I
authors.lastname: Miloslavskaya
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Theodore
authors.initials: T
authors.lastname: Chiang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Haley
authors.initials: H
authors.lastname: Streff
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: John R
authors.initials: JR
authors.lastname: Seavitt
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Murray
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.|Baylor Miraca Genetics Laboratories, Houston, Texas.
authors.forename: Christine
authors.initials: C
authors.lastname: Eng
authors.affiliation: Department of Dermatology, Texas Children's Hospital, Houston, Texas.
authors.forename: Audrey
authors.initials: A
authors.lastname: Chan
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.|Baylor Miraca Genetics Laboratories, Houston, Texas.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Seema R
authors.initials: SR
authors.lastname: Lalani
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004392:Dwarfism / Q000175:diagnosis / Q000235:genetics; D005091:Exons; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D017384:Sequence Deletion
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C112203:CRIPT protein, human
keywords: CRIPT mutation; genome wide microarray; microcephaly; postnatal growth retardation; whole exome sequencing