Identification by array-Comparative Genomic Hybridization (array-CGH) of a large deletion of luteinizing hormone receptor gene combined with a missense mutation in a patient diagnosed with a 46,XY disorder of sex development and application to prenatal diagnosis

Nicolas Richard; Céline Leprince; Nicolas Gruchy; Pascal Pigny; Joris Andrieux; Hervé Mittre; Sylvie Manouvrier; Najiba Lahlou; Jacques Weill; Marie-Laure Kottler

doi:10.1507/endocrj.K11E-119

ORIGINALS

Identification by array-Comparative Genomic Hybridization (array-CGH) of a large deletion of luteinizing hormone receptor gene combined with a missense mutation in a patient diagnosed with a 46,XY disorder of sex development and application to prenatal diagnosis

Nicolas Richard, Céline Leprince, Nicolas Gruchy, Pascal Pigny, Joris Andrieux, Hervé Mittre, Sylvie Manouvrier, Najiba Lahlou, Jacques Weill, Marie-Laure Kottler

Author information

Nicolas Richard
Department of Genetics, Caen University Hospital, Caen, France
IFR 146 ICORE - EA 2608, Caen University, Caen, France
Céline Leprince
Department of Genetics, Caen University Hospital, Caen, France
Nicolas Gruchy
Department of Genetics, Caen University Hospital, Caen, France
Pascal Pigny
Biology and Pathology Center, Lille University Hospital, Lille, France
Joris Andrieux
Biology and Pathology Center, Lille University Hospital, Lille, France
Hervé Mittre
Department of Genetics, Caen University Hospital, Caen, France
IFR 146 ICORE - EA 2608, Caen University, Caen, France
Sylvie Manouvrier
Department of Clinical Genetics, Lille University Hospital, Lille, France
Najiba Lahlou
Department of Hormonal Biology, Cochin University Hospital, Paris, France
Jacques Weill
Department of Pediatrics, Lille University Hospital, Lille, France
Marie-Laure Kottler
Department of Genetics, Caen University Hospital, Caen, France
IFR 146 ICORE - EA 2608, Caen University, Caen, France

Keywords: 46,XY disorders of sex development, Inactivating mutation, LHCGR gene, Prenatal diagnosis, array-Comparative Genomic Hybridization

JOURNAL FREE ACCESS

2011 Volume 58 Issue 9 Pages 769-776

DOI https://doi.org/10.1507/endocrj.K11E-119

View "Advance Publication" version (June 30, 2011).

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Abstract

This paper reports the case of an infant presenting with sexual ambiguity at birth. The child presented with labia majora synechia, thready genital tubercle and perineal hypospadias. The karyotype was 46,XY. Low testosterone levels with no response to hCG administration, associated with high LH level for her age, high FSH level, high inhibin B levels and normal AMH indicated a lack of LH receptivity and prompted us to screen the LHCGR gene for mutations. A previously described missense mutation (p.Cys131Arg) was identified at homozygous state in the propositus and at heterozygous state in the mother. This variation, however, was not found in the father. Our attention was drawn by the presence of several single nucleotide polymorphisms (SNPs), identified at homozygous state without any paternal contribution from exon 1 to exon 10 of LHCGR, suggesting a paternal deletion. Array DNA analysis was performed revealing a large deletion extending from 61,493 to 135,344 bp and including the LHCGR gene. Adequate genetic counselling was provided. This paper describes the first application of prenatal diagnosis in LHCGR deficiency for 46,XY disorders of sex development with the subsequent delivery of a normal baby.

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