title: 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.
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.
authors: Department of Genetics, Caen University Hospital, Avenue Clemenceau, Caen, France.
authors: Nicolas
authors: N
authors: Richard
authors: Céline
authors: C
authors: Leprince
authors: Nicolas
authors: N
authors: Gruchy
authors: Pascal
authors: P
authors: Pigny
authors: Joris
authors: J
authors: Andrieux
authors: Hervé
authors: H
authors: Mittre
authors: Sylvie
authors: S
authors: Manouvrier
authors: Najiba
authors: N
authors: Lahlou
authors: Jacques
authors: J
authors: Weill
authors: Marie-Laure
authors: ML
authors: Kottler
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D004247:DNA / Q000737:chemistry / Q000235:genetics; D058490:Disorder of Sex Development, 46,XY / Q000097:blood / Q000235:genetics*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011296:Prenatal Diagnosis / Q000379:methods; D011974:Receptors, LH / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D013739:Testosterone / Q000097:blood
chemical_list: D011974:Receptors, LH; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004247:DNA