Document Detail


Homozygous mutation of the IGF1 receptor gene in a patient with severe pre- and postnatal growth failure and congenital malformations.
MedLine Citation:
PMID:  23045302     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Heterozygous mutations in the IGF1 receptor (IGF1R) gene lead to partial resistance to IGF1 and contribute to intrauterine growth retardation (IUGR) with postnatal growth failure. To date, homozygous mutations of this receptor have not been described.
SUBJECT: A 13.5-year-old girl born from healthy first-cousin parents presented with severe IUGR and persistent short stature. Mild intellectual impairment, dysmorphic features, acanthosis nigricans, and cardiac malformations were also present.
METHODS: Auxological and endocrinological profiles were measured. All coding regions of the IGF1R gene including intron boundaries were amplified and directly sequenced. Functional characterization was performed by immunoblotting using patient's fibroblasts.
RESULTS: IGF1 level was elevated at 950NG/ML (+7 S.D.). Fasting glucose level was normal associated with high insulin levels at baseline and during an oral glucose tolerance test. Fasting triglyceride levels were elevated. sequencing of the IGF1R gene led to the identification of a homozygous variation in exon 2: c.119G>T (p.Arg10Leu). As a consequence, IGF1-dependent receptor autophosphorylation and downstream signaling were reduced in patient's fibroblasts. Both parents were heterozygous for the mutation.
CONCLUSION: The homozygous mutation of the IGF1R is associated with severe IUGR, dysmorphic features, and insulin resistance, while both parents were asymptomatic heterozygous carriers of the same mutation.
Authors:
Marie-Hélène Gannagé-Yared; Jürgen Klammt; Eliane Chouery; Sandra Corbani; Hala Mégarbané; Joelle Abou Ghoch; Nancy Choucair; Roland Pfäffle; André Mégarbané
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-12-10
Journal Detail:
Title:  European journal of endocrinology / European Federation of Endocrine Societies     Volume:  168     ISSN:  1479-683X     ISO Abbreviation:  Eur. J. Endocrinol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-11     Completed Date:  2013-02-04     Revised Date:  2013-05-08    
Medline Journal Info:
Nlm Unique ID:  9423848     Medline TA:  Eur J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  K1-7     Citation Subset:  IM    
Affiliation:
Service d'Endocrinologie, Hôtel-Dieu de France Hospital, Beirut, Lebanon.
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Multiple / genetics
Adolescent
Child, Preschool
Failure to Thrive / genetics*
Female
Fetal Growth Retardation / genetics
Heterozygote
Homozygote
Humans
Insulin Resistance / genetics
Intellectual Disability / genetics
Models, Molecular
Receptor, IGF Type 1 / genetics*
Chemical
Reg. No./Substance:
EC 2.7.10.1/Receptor, IGF Type 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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