Universität zu Köln

Moosa, Shahida ORCID: 0000-0002-4463-3067, Boehrer-Rabel, Helena, Altmueller, Janine, Beleggia, Filippo ORCID: 0000-0003-0234-7094, Nuernberg, Peter, Li, Yun, Yigit, Goekhan and Wollnik, Bernd (2017). Smith-Kingsmore Syndrome: A Third Family with the MTOR Mutation C.5395G > A p.(Glu1799Lys) and Evidence for Paternal Gonadal Mosaicism. Am. J. Med. Genet. A, 173 (1). S. 264 - 268. HOBOKEN: WILEY. ISSN 1552-4833

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Abstract

Heterozygous germline mutations in MTOR have been shown to underlie Smith-Kingsmore syndrome, a rare autosomal dominant syndrome characterized by macrocephaly, developmental delay, and dysmorphic facial features. Recently, two unrelated families with the MTOR mutation, c.5395G>A p.(Glu1799Lys), were reported. Here, we describe siblings from a non-consanguineous German family in whom we identified the same heterozygous missense mutation in MTOR. Remarkably, in all reported families with Smith-Kingsmore syndrome and the MTOR c.5395G>A mutation, including the family described herein, healthy parents of recurrently affected children do not have detectable levels of the mutation in tested tissues, lending credence to gonadal mosaicism as the underlying mechanism. Furthermore, the glutamic acid at position 1799 was shown to present a recurrent somatic mutation site in several cancers, including colon cancer, pointing to a somatic mutational hotspot in MTOR. Importantly, we highlight the occurrence of multiple intestinal polyps in the older sibling. Further patients are required to establish definitively whether polyp formation forms part of the SKS clinical spectrum. (C) 2016 Wiley Periodicals, Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Moosa, Shahida UNSPECIFIED orcid.org/0000-0002-4463-3067 UNSPECIFIED Boehrer-Rabel, Helena UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Beleggia, Filippo UNSPECIFIED orcid.org/0000-0003-0234-7094 UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Yun UNSPECIFIED UNSPECIFIED UNSPECIFIED Yigit, Goekhan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wollnik, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-247664
DOI:	10.1002/ajmg.a.37999
Journal or Publication Title:	Am. J. Med. Genet. A
Volume:	173
Number:	1
Page Range:	S. 264 - 268
Date:	2017
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1552-4833
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24766