Mutations of SGO2 and CLDN14 collectively cause coincidental Perrault syndrome.

Research output: Contribution to journalArticle

  • External authors:
  • Rabia Faridi
  • Atteeq U. Rehman
  • Robert J. Morell
  • Penelope E. Friedman
  • Sana Zahra
  • Asma Ali Khan
  • Dalia Tohlob
  • Muhammad Zaman Assir
  • Shaheen N Khan
  • Sheikh Riazuddin
  • Thomas B. Friedman


Perrault syndrome (PS) is a genetically heterogeneous disorder characterized by primary ovarian insufficiency (POI) in females and sensorineural hearing loss in males and females. In many PS subjects, causative variants have not been found in the five reported PS genes. The objective of this study was to identify the genetic cause of PS in an extended consanguineous family with six deaf individuals. Whole exome sequencing (WES) was completed on four affected members of a large family, and variants and co-segregation was confirmed by Sanger sequencing. All hearing impaired individuals, including the proband, are homozygous for a pathogenic variant of CLDN14, but this only explains the deafness. The PS proband is also homozygous for a frameshift variant (c.1453_1454delGA, p.Glu485Lysfs*5) in exon 7 of SGO2 encoding shugoshin 2, which is the likely cause of her concurrent ovarian insufficiency. In mouse, Sgol2a encoding shugoshin-like 2a is necessary during meiosis in both sexes to maintain the integrity of the cohesin complex that tethers sister chromatids. Human SGO2 has not previously been implicated in any disorder, but in this case of POI and perhaps others, it is a candidate for unexplained infertility.

Bibliographical metadata

Original languageEnglish
Number of pages15
JournalClinical Genetics
Early online date15 Sep 2016
Publication statusPublished - 2016