Variants in congenital hypogonadotrophic hypogonadism genes identified in an Indonesian cohort of 46,XY under-virilised boys

Congenital hypogonadotrophic hypogonadism (CHH) and Kallmann syndrome (KS) are caused by disruption to the hypothalamic-pituitary-gonadal (H-P-G) axis. In particular, reduced production, secretion or action of gonadotrophin-releasing hormone (GnRH) is often responsible. Various genes, many of which...

Full description

Saved in:
Bibliographic Details
Published in:Human genomics 2017-02, Vol.11 (1), p.1-1, Article 1
Main Authors: Ayers, Katie L, Bouty, Aurore, Robevska, Gorjana, van den Bergen, Jocelyn A, Juniarto, Achmad Zulfa, Listyasari, Nurin Aisyiyah, Sinclair, Andrew H, Faradz, Sultana M H
Format: Article
Language:English
Subjects:
Adolescent
Child
Child, Preschool
Cohort Studies
DNA Helicases - genetics
DNA-Binding Proteins - genetics
Gastrointestinal Hormones - genetics
Humans
Hypogonadism - congenital
Hypogonadism - genetics
Hypogonadism - pathology
Indonesia
Infant
Male
Membrane Proteins - genetics
Mutation
Neuropeptides - genetics
Primary Research
Proto-Oncogene Proteins - genetics
Receptor, Fibroblast Growth Factor, Type 1 - genetics
Receptors, G-Protein-Coupled - genetics
Receptors, Peptide - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Congenital hypogonadotrophic hypogonadism (CHH) and Kallmann syndrome (KS) are caused by disruption to the hypothalamic-pituitary-gonadal (H-P-G) axis. In particular, reduced production, secretion or action of gonadotrophin-releasing hormone (GnRH) is often responsible. Various genes, many of which play a role in the development and function of the GnRH neurons, have been implicated in these disorders. Clinically, CHH and KS are heterogeneous; however, in 46,XY patients, they can be characterised by under-virilisation phenotypes such as cryptorchidism and micropenis or delayed puberty. In rare cases, hypospadias may also be present. Here, we describe genetic mutational analysis of CHH genes in Indonesian 46,XY disorder of sex development patients with under-virilisation. We present 11 male patients with varying degrees of under-virilisation who have rare variants in known CHH genes. Interestingly, many of these patients had hypospadias. We postulate that variants in CHH genes, in particular PROKR2, PROK2, WDR11 and FGFR1 with CHD7, may contribute to under-virilisation phenotypes including hypospadias in Indonesia.
ISSN:1479-7364
1473-9542
1479-7364
DOI:10.1186/s40246-017-0098-2