Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/62960
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Type: Journal article
Title: Hypomorphic temperature-sensitive alleles of NSDHL cause CK syndrome
Author: Gecz, J.
Citation: American Journal of Human Genetics, 2010; 87(6):905-914
Publisher: Univ Chicago Press
Issue Date: 2010
ISSN: 0002-9297
1537-6605
Statement of
Responsibility: 
Keith W. McLarren... Jozef Gecz... et al.
Abstract: CK syndrome (CKS) is an X-linked recessive intellectual disability syndrome characterized by dysmorphism, cortical brain malformations, and an asthenic build. Through an X chromosome single-nucleotide variant scan in the first reported family, we identified linkage to a 5 Mb region on Xq28. Sequencing of this region detected a segregating 3 bp deletion (c.696_698del [p.Lys232del]) in exon 7 of NAD(P) dependent steroid dehydrogenase-like (NSDHL), a gene that encodes an enzyme in the cholesterol biosynthesis pathway. We also found that males with intellectual disability in another reported family with an NSDHL mutation (c.1098 dup [p.Arg367SerfsX33]) have CKS. These two mutations, which alter protein folding, show temperature-sensitive protein stability and complementation in Erg26-deficient yeast. As described for the allelic disorder CHILD syndrome, cells and cerebrospinal fluid from CKS patients have increased methyl sterol levels. We hypothesize that methyl sterol accumulation, not only cholesterol deficiency, causes CKS, given that cerebrospinal fluid cholesterol, plasma cholesterol, and plasma 24S-hydroxycholesterol levels are normal in males with CKS. In summary, CKS expands the spectrum of cholesterol-related disorders and insight into the role of cholesterol in human development.
Keywords: Animals; Humans; Abnormalities, Multiple; Genetic Diseases, X-Linked; 3-Hydroxysteroid Dehydrogenases; Pedigree; Temperature; Amino Acid Sequence; Sequence Homology, Amino Acid; Mutation; Alleles; Exons; Molecular Sequence Data; Adolescent; Adult; Female; Male; Young Adult
Rights: © 2010 by The American Society of Human Genetics. All rights reserved.
RMID: 0020102205
DOI: 10.1016/j.ajhg.2010.11.004
Appears in Collections:Paediatrics publications

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