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:
CreatorsEmailORCIDORCID Put Code
Grosse, GretaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hilger, AlinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ludwig, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reutter, HeikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lorenzen, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Even, GertrudUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holterhus, Paul-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woelfle, JoachimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
SHORT STATURE; NOONAN-SYNDROME; HORMONE; MUTATIONS; DIAGNOSIS; VARIANTS; GENETICS; DISEASE; GHRMultiple languages
Endocrinology & Metabolism; PediatricsMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/24476

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