Universität zu Köln

Lessel, Davor ORCID: 0000-0003-4496-244X, Saha, Bidisha, Hisama, Fuki, Kaymakamzade, Bahar, Nurlu, Gulay, Gursoy-Oezdemir, Yasemin, Thiele, Holger, Nuernberg, Peter, Martin, George M., Kubisch, Christian ORCID: 0000-0003-4220-0978 and Oshima, Junko (2014). Atypical Aicardi-Goutieres Syndrome: Is the WRN Locus a Modifier? Am. J. Med. Genet. A, 164 (10). S. 2510 - 2514. HOBOKEN: WILEY-BLACKWELL. ISSN 1552-4833

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Abstract

We describe a 28-year-old Turkish man with consanguineous parents who presented with an aged appearance with prematurely gray hair and scleroderma-like skin, spastic paraplegia, and apparent disability. The proband and each of his parents were heterozygous for a mutation in WRN, which could not explain his symptoms. Exome sequencing of the proband's blood DNA showed a homozygous c.626-1G>C mutation in intron 5 of the SAMHD1 gene, which encodes a triphosphohydrolase involved in the regulation of intracellular dNTP pools and which is mutated in Aicardi-Goutieres syndrome. The RNA studies confirmed aberrant splicing of exon 6, and family studies showed that both parents are heterozygous for this mutation. We conclude that mutations in SAMHD1-in addition to causing an early-onset form of encephalopathy in Aicardi-Goutieres syndrome -may present with modest signs of accelerated aging similar to Werner syndrome. The extent to which heterozygosity at the WRN locus may modify the effect of biallelic SAMHD1 mutations is unknown. It is conceivable that synergistic effects of these two mutations might be responsible for the unusual phenotype. (C) 2014 Wiley Periodicals, Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lessel, Davor UNSPECIFIED orcid.org/0000-0003-4496-244X UNSPECIFIED Saha, Bidisha UNSPECIFIED UNSPECIFIED UNSPECIFIED Hisama, Fuki UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaymakamzade, Bahar UNSPECIFIED UNSPECIFIED UNSPECIFIED Nurlu, Gulay UNSPECIFIED UNSPECIFIED UNSPECIFIED Gursoy-Oezdemir, Yasemin UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, George M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kubisch, Christian UNSPECIFIED orcid.org/0000-0003-4220-0978 UNSPECIFIED Oshima, Junko UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-427809
DOI:	10.1002/ajmg.a.36664
Journal or Publication Title:	Am. J. Med. Genet. A
Volume:	164
Number:	10
Page Range:	S. 2510 - 2514
Date:	2014
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1552-4833
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SAMHD1; MUTATIONS; STROKE Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42780