Isolated Hypogonadotropic Hypogonadism with SOX2 Mutation and Anophthalmia/microphthalmia in Offspring

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2011 Feb 18

PMID 21326281

Citations 12

Authors

Zornitza Stark

Rebecca Storen

Bruce Bennetts

Ravi Savarirayan

Robyn V Jamieson

Affiliations

Soon will be listed here.

Abstract

Isolated hypogonadotropic hypogonadism (IHH) is a genetically heterogeneous condition in which patients frequently require assisted reproduction to achieve fertility. In patients with IHH who are otherwise well, no particular increased risk of congenital anomalies in the resultant offspring has been highlighted. Heterozygous mutations in SOX2 are the commonest single-gene cause of anophthalmia/microphthalmia (A/M) and sometimes result in pituitary abnormalities. We report a family with a novel frameshift mutation in the SOX2 transactivation domain, p.Gly280AlafsX91, resulting in bilateral anophthalmia and subtle endocrinological abnormalities in a male sibling, and unilateral microphthalmia in a female sibling. The mutation is present in their mother who has IHH, but has no eye disorders or other anomalies. She underwent assisted reproduction to achieve fertility. This report has important implications for the evaluation of patients with IHH, particularly in the setting of planned infertility treatment.

Citing Articles

A novel frameshift pathogenic variant located in the transactivation domain in a male infant with hypogonadotropic hypogonadism.

Kimura-Yoshida A, Sato T, Ichihashi Y, Wasa M, Narumi S, Ishii T Clin Pediatr Endocrinol. 2024; 33(4):244-248.

PMID: 39359665 PMC: 11442697. DOI: 10.1297/cpe.2024-0013.

Heterozygous mutations in SOX2 may cause idiopathic hypogonadotropic hypogonadism via dominant-negative mechanisms.

Cassin J, Stamou M, Keefe K, Sung K, Bojo C, Tonsfeldt K JCI Insight. 2023; 8(3).

PMID: 36602867 PMC: 9977424. DOI: 10.1172/jci.insight.164324.

Growth hormone deficiency in a case of septo-optic-dysplasia due to mutation: should we re-test patients during the transition period?.

Gasco V, Matarazzo P, de Sanctis L, Ghigo E BMJ Case Rep. 2022; 15(12).

PMID: 36581364 PMC: 9806035. DOI: 10.1136/bcr-2022-251897.

Review of 37 patients with SOX2 pathogenic variants collected by the Anophthalmia/Microphthalmia Clinical Registry and DNA research study.

Amlie-Wolf L, Bardakjian T, Kopinsky S, Reis L, Semina E, Schneider A Am J Med Genet A. 2021; 188(1):187-198.

PMID: 34562068 PMC: 9169870. DOI: 10.1002/ajmg.a.62518.

Congenital Hypopituitarism During the Neonatal Period: Epidemiology, Pathogenesis, Therapeutic Options, and Outcome.

Bosch I Ara L, Katugampola H, Dattani M Front Pediatr. 2021; 8:600962.

PMID: 33634051 PMC: 7902025. DOI: 10.3389/fped.2020.600962.

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