title: A novel mutation of the insulin-like 3 gene in patients with cryptorchidism.
abstract: Two independent studies demonstrated that transgenic mice with a targeted deletion of the insulin-like 3 ( INSL3) gene presented bilateral cryptorchidism. Studies in humans have investigated the possibility that mutations in the INSL3 gene are the cause of cryptorchidism. In the present study, genomic DNA was obtained from 150 patients with idiopathic cryptorchidism. DNA was amplified and the polymerase chain reaction products of both exons were sequenced. A previously unidentified missense mutation was found in only one of the patients studied. In exon 2, a heterozygous C/G substitution at nucleotide 2560, which turned asparagine into lysine at codon 86, was documented. The familial study revealed that the mother was a heterozygous carrier of the mutation and the father was a homozygote wild type. We also found three polymorphic changes, previously reported in exon 1. The Asn-into-Lys change is likely deleterious because it leads to a nonconservative amino acid substitution, changing a highly conserved residue. This mutation, located in the A-chain of the INSL3 protein, is the first mutation reported in this region. This finding provides new evidence that INSL3 is involved in testicular descent in humans; however, mutations of this gene are not a frequent cause of cryptorchidism.
authors.affiliation: Research Unit in Developmental Biology, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, D.F., México.
authors.forename: Patricia
authors.initials: P
authors.lastname: Canto
authors.forename: Irineo
authors.initials: I
authors.lastname: Escudero
authors.forename: Daniela
authors.initials: D
authors.lastname: Söderlund
authors.forename: Elisa
authors.initials: E
authors.lastname: Nishimura
authors.forename: Sebastian
authors.initials: S
authors.lastname: Carranza-Lira
authors.forename: Jesus
authors.initials: J
authors.lastname: Gutierrez
authors.forename: Andres
authors.initials: A
authors.lastname: Nava
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Mendez
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D017124:Conserved Sequence; D003456:Cryptorchidism / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007328:Insulin; D008297:Male; D020125:Mutation, Missense; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins