Mutations in a novel, cryptic exon of the luteinizing hormone/chorionic gonadotropin receptor gene cause male pseudohermaphroditism.

PLoS Medicine
Nina KossackJörg Gromoll

Abstract

Male pseudohermaphroditism, or Leydig cell hypoplasia (LCH), is an autosomal recessive disorder in individuals with a 46,XY karyotype, characterized by a predominantly female phenotype, a blind-ending vagina, absence of breast development, primary amenorrhea, and the presence of testicular structures. It is caused by mutations in the luteinizing hormone/chorionic gonadotropin receptor gene (LHCGR), which impair either LH/CG binding or signal transduction. However, molecular analysis has revealed that the LHCGR is apparently normal in about 50% of patients with the full clinical phenotype of LCH. We therefore searched the LHCGR for novel genomic elements causative for LCH. In the present study we have identified a novel, primate-specific bona fide exon (exon 6A) within the LHCGR gene. It displays composite characteristics of an internal/terminal exon and possesses stop codons triggering nonsense-mediated mRNA decay (NMD) in LHCGR. Transcripts including exon 6A are physiologically highly expressed in human testes and granulosa cells, and result in an intracellular, truncated LHCGR protein of 209 amino acids. We sequenced exon 6A in 16 patients with unexplained LCH and detected mutations in three patients. Functional studies revea...Continue Reading

References

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Citations

May 23, 2014·Journal of Assisted Reproduction and Genetics·Frederic MitriRobert F Casper
Oct 20, 2009·The Journal of Clinical Endocrinology and Metabolism·Paul A FowlerPeter J O'Shaughnessy
May 26, 2011·Nucleic Acids Research·Jana KralovicovaIgor Vorechovsky
May 21, 2013·Human Reproduction Update·Britta TroppmannJörg Gromoll
Dec 13, 2012·Molecular and Cellular Endocrinology·Nina KossackJörg Gromoll
Aug 12, 2014·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·Manuel NistalMiguel Reyes-Múgica
Mar 15, 2015·Frontiers in Endocrinology·Claire CahoreauYves Combarnous
Apr 30, 2017·International Journal of Molecular Sciences·Livio CasariniManuela Simoni
Oct 17, 2018·The Aging Male : the Official Journal of the International Society for the Study of the Aging Male·Helen ZirnaskKersti Kokk
Feb 5, 2011·Molecular Endocrinology·Annika KreuchwigGerd Krause
Jul 14, 2020·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Amine Aktar KarakayaYusuf Kenan Haspolat
Oct 29, 2021·Molecular Genetics & Genomic Medicine·Niall Patrick Keegan, Sue Fletcher

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Datasets Mentioned

BETA
CD766751

Methods Mentioned

BETA
Reverse Transcription PCR
transfection
FCS
PCR
electrophoresis

Software Mentioned

FASTA
BLAST
ClustalW
ESE finder

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