ESPE Abstracts (2015) 84 P-2-518

A Novel Single Nucleotide Variation Contributing to the Expression of Isolated Hypogonadotropic Hypogonadism

Ahmed Khattaba, Cuiqi Zhoub, Maria Newa & Shlomo Melmedb

aIcahn School of Medicine at Mount Sinai, New York, NY, USA; bCedars-Sinai Medical Center, Los Angeles, CA, USA

Background: The molecular genetics of isolated hypogonadotropic hypogonadism (IHH) has been a subject of interest and recent discoveries. Multiple genetic variants with x-linked and autosomal inheritance are involved in the regulation of the hypothalamic pituitary gonadal axis.

Objective and hypotheses: We undertook an extensive genetic evaluation to elucidate a possible genetic aetiology in two brothers with clinical and biochemical evidence of IHH. We hypothesize that polymorphic genetic variation is responsible for the phenotypic expression of IHH in our patients.

Method: Whole exon sequencing of genomic DNA followed by SNV of interest validation using PCR was performed. Seven genes derived from sequencing results were selected for further validation. The selected genes contained coding region SNV(s) and were associated with the hypothalamic-pituitary axis and the patient’s clinical phenotype.

Results: More than 600 SNPs were observed in >70 different genes; No SNPs were found in the GnRH receptor gene; nine SNPs in seven x-linked genes were validated by PCR; Of the nine valid polymorphisms, eight produced an amino acid change; All selected SNVs were known in the NCBI database.

Conclusion: Patients both have IHH, while they only have the same SNV in one gene (MAMLD1 exon 3).

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