ECE2016 Eposter Presentations Neuroendocrinology (43 abstracts)
Phenotype-genotype analysis in patients with GnRH deficiency in a single center
Sandra Pekic Djurdjevic 1, , Cheng Xu 3 , Andrew Dwyer 3 , Daniele Cassatella 3 , Mirjana Doknic 1, , Dragana Miljic 1, , Marko Stojanovic 1, , Milan Petakov 1, , Nelly Pitteloud 3 & Vera Popovic 1,
1Department of Neuroendocrinology, Clinic for Endocrinology, Diabetes and Diseases of Metabolism, University Clinical Center, Belgrade, Serbia; 2School of Medicine, University of Belgrade, Belgrade, Serbia; 3Endocrinology, Diabetes and Metabolism Sevice of the Centre Hospitalier Universitaire Vaudois (CHUV), du Bugnon 46, Lausanne 1011, Switzerland.
Objective: Congenital hypogonadotropic hypogonadism (CHH) results from isolated GnRH deficiency and may present with normal sense of smell (nCHH), anosmia (Kallmann syndrome, KS) or in syndromic forms. Genetic defects are identified in approximately half of CHH cases and oligogenicity is noted in almost 10%. Further, spontaneous reversal of is seen in 15% of patients.
Methods: We analyzed the clinical characteristics of 37 Serbian CHH probands (34 sporadic, 3 familial). Genetic analyses were conducted in 15 probands. Rare variants (minor allele frequency <1%) were considered mutations if they were nonsense, frameshift, splice-site-altering variants or missense variants predicted to be deleterious in silico.
Results: In total, 11/37 (30%) had KS, 22/37 (59%) were nCHH, and 4 were syndromic (n=2 4H syndrome: HH/hypomyelination/hypodontia, n=1 CHARGE syndrome: coloboma/heart defects/atresia of choanae/retarded growth/genital anomalies/ear defects, n=1 HH+adrenal hypoplasia). Three male reversal cases were noted among the 33 KS/nCHH (10%). Genetic studies revealed mutations in 11 different loci in 12/15 (80%) unrelated probands. Two of three reversal cases were found to carry heterozygous mutations (FGFR1 and TACR3 respectively) and all three familial cases (2 nCHH, 1 KS) were found to harbor heterozygous mutations in FGFR1. Among the syndromic cases, both patients with 4H Syndrome harbor heterozygous mutations in POLR3 while the patient with HH+adrenal hypoplasia has a hemizygous mutation in NR0B1. Exome sequencing revealed oligogenicity in one familial nCHH case (1/11, 10%) who harbors heterozygous mutations in FGFR1, GNRH1, and LEP.
Conclusions: This CHH cohort displays marked clinical heterogeneity including patients with 4H syndrome, CHARGE syndrome and congenital adrenal hypoplasia. We identified mutations in the majority (80%) of cases. Those patients without mutations did not exhibit any CHH-associated phenotypes. Exome sequencing is an efficient and effective tool for exploring the complex genetic architecture of CHH.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more