Universität zu Köln

Grosse, Greta, Hilger, Alina, Ludwig, Michael, Reutter, Heiko, Lorenzen, Franziska, Even, Gertrud, Holterhus, Paul-Martin and Woelfle, Joachim (2017). Targeted Resequencing of Putative Growth-Related Genes Using Whole Exome Sequencing in Patients with Severe Primary IGF-I Deficiency. Horm. Res. Paediatr., 88 (6). S. 408 - 418. BASEL: KARGER. ISSN 1663-2826

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Abstract

Background/Aims: To elucidate the genetic causes of severe primary insulin-like growth factor-I deficiency (SPIGFD) by systematic, targeted, next-generation sequencing (NGS)based resequencing of growth-related genes. Methods: Clinical phenotyping followed by NGS in 17 families including 6 affected sib pairs. Results: We identified disease-causing, heterozygous, de novo variants in HRAS (p.Gly13Cys) and FAM111A (p.Arg569His) in 2 male patients with syndromic SPIGFD. A previously described homozygous GHR nonsense variant was detected in 2 siblings of a consanguineous family (p.Glu198*). Furthermore, we identified an inherited novel variant in the IGF2 gene (p.Arg156Cys) of a maternally imprinted gene in a less severely affected father and his affected daughter. We detected 2 other novel missense variants in SH2B1 and SOCS2, both were inherited from an unaffected parent. Conclusions: Screening of growth-related genes using NGS-based, large-scale, targeted resequencing identified disease-causing variants in HRAS, FAM111A, and GHR. Considering the increased risk of subjects with HRAS mutations for neoplasms, close clinical monitoring and a thorough discussion of the risk/benefit ratio of the treatment with recombinant IGF-I is mandatory. Segregation analysis proved to be critical in the interpretation of potential SPIGFD-associated gene variations. (C) 2017 S. Karger AG, Basel

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Grosse, Greta UNSPECIFIED UNSPECIFIED UNSPECIFIED Hilger, Alina UNSPECIFIED UNSPECIFIED UNSPECIFIED Ludwig, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Reutter, Heiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Lorenzen, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Even, Gertrud UNSPECIFIED UNSPECIFIED UNSPECIFIED Holterhus, Paul-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Woelfle, Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-244763
DOI:	10.1159/000480505
Journal or Publication Title:	Horm. Res. Paediatr.
Volume:	88
Number:	6
Page Range:	S. 408 - 418
Date:	2017
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	1663-2826
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SHORT STATURE; NOONAN-SYNDROME; HORMONE; MUTATIONS; DIAGNOSIS; VARIANTS; GENETICS; DISEASE; GHR Multiple languages Endocrinology & Metabolism; Pediatrics Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24476