Whole Exome Sequencing of a Consanguineous Turkish Family Identifies a Mutation in GTF2H3 in Brothers With Spermatogenic Failure

Raul I Clavijo, Himanshu Arora, Eric Gibbs, Samuel Cohen, Anthony Griswold, Emre Bakircioglu, Guney Bademci, Mustafa Tekin, Ranjith Ramasamy

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

In this case report we describe our investigation into the genetic cause of infertility due to idiopathic nonobstructive azoospermia in a consanguineous Turkish family. We extracted DNA from blood and applied whole exome sequencing on 4 infertile brothers in this family diagnosed with oligo- and azoospermia. Standard bioinformatics analysis pipelines were run including alignment to the reference genome, variant calling, and quality control filtering. Potentially pathogenic variants were identified and prioritized using genetic variant annotation software and public variant frequency databases, followed by validation with Sanger sequencing. A nonsynonymous variant in “general transcription factor TFIIH subunit 3” (GTF2H3) was identified in this consanguineous family. This variant in chromosome 12 (12chr: 124144111 T>C, p.Ser222Pro) of GTF2H3 represents a likely a disease-causing mutation as it is predicted to be damaging, rare, segregates with the disease, and is highly evolutionarily conserved. Familial segregation analysis of the variant showed that it was present as a homozygous mutation in the brothers with nonobstructive azoospermia, and heterozygous mutation in the oligospermic brothers. We propose a mechanism by which this variant leads to deficits in Vitamin A signaling, which is essential for spermatogenesis.

Original languageEnglish (US)
JournalUrology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Exome
Mutation
Transcription Factor TFIIH
General Transcription Factors
Oligospermia
Chromosomes, Human, Pair 12
Azoospermia
Spermatogenesis
Computational Biology
Vitamin A
Quality Control
Infertility
Software
Genome
Databases
DNA
Nonobstructive Azoospermia

ASJC Scopus subject areas

  • Urology

Cite this

Whole Exome Sequencing of a Consanguineous Turkish Family Identifies a Mutation in GTF2H3 in Brothers With Spermatogenic Failure. / Clavijo, Raul I; Arora, Himanshu; Gibbs, Eric; Cohen, Samuel; Griswold, Anthony; Bakircioglu, Emre; Bademci, Guney; Tekin, Mustafa; Ramasamy, Ranjith.

In: Urology, 01.01.2018.

Research output: Contribution to journalArticle

Clavijo, Raul I ; Arora, Himanshu ; Gibbs, Eric ; Cohen, Samuel ; Griswold, Anthony ; Bakircioglu, Emre ; Bademci, Guney ; Tekin, Mustafa ; Ramasamy, Ranjith. / Whole Exome Sequencing of a Consanguineous Turkish Family Identifies a Mutation in GTF2H3 in Brothers With Spermatogenic Failure. In: Urology. 2018.
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