Toggle Main Menu Toggle Search

Open Access padlockePrints

Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies

Lookup NU author(s): Dr Richard Quinton


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Background A constellation of neurodegenerative disorders exists (Gordon Holmes syndrome, 4H leucodystrophy, Boucher-Neuhauser syndrome) in which patients suffer from both neurological disease (typically manifested by ataxia) and reproductive failure (idiopathic hypogonadotropic hypogonadism (IHH)). POLR3B, which encodes the second largest subunit of RNA polymerase III (pol III), and POLR3A, which forms the pol III catalytic centre, are associated with 4H leucodystrophy.Methods Whole exome sequencing was performed on a large cohort of subjects with IHH (n=565). Detailed neuroendocrine studies were performed in some individuals within this cohort.Results Four individuals (two of them siblings) were identified with two rare nucleotide variants in POLR3B. On initial evaluation, all subjects were free of neurological disease. One patient underwent treatment with exogenous pulsatile gonadotropin-releasing hormone for 8 weeks which failed to result in normalisation of his sex steroid milieu due to pituitary resistance.Conclusions These findings suggest that the spectrum of phenotypes resulting from POLR3B mutations is wider than previously believed and that POLR3B can be associated exclusively with disorders characterised by abnormal gonadotropin secretion.

Publication metadata

Author(s): Richards MR, Plummer L, Chan YM, Lippincott MF, Quinton R, Kumanov P, Seminara SB

Publication type: Article

Publication status: Published

Journal: Journal of Medical Genetics

Year: 2017

Volume: 54

Issue: 1

Pages: 19-25

Print publication date: 01/01/2017

Online publication date: 10/08/2016

Acceptance date: 21/07/2016

ISSN (print): 0022-2593

ISSN (electronic): 1468-6244

Publisher: BMJ Publishing Group


DOI: 10.1136/jmedgenet-2016-104064


Altmetrics provided by Altmetric


Funder referenceFunder name
P50HD028138National Institutes of Health Eunice Kennecy Shriver National Institute of Child Health and Human Development