title: Molecular analysis of the insulin receptor gene for prenatal diagnosis of leprechaunism in two families.
abstract: Leprechaunism is a rare autosomal recessive disorder characterized by marked intrauterine and postnatal growth retardation, severe insulin resistance, and altered glucose homeostasis. This syndrome is related to mutations in the insulin receptor (IR) gene that impair the transmission of the insulin signal by several mechanisms. There is no effective therapy and patients usually die within the first months of life. Here we report the prenatal diagnosis of leprechaunism in two unrelated families in which affected children were compound heterozygotes with two different deficient IR alleles. In family Par-1, the disease IR alleles carried a missense mutation located in exon 18 (Arg1092-->Trp) and exon 20 (Glu1179-->Lys). In family Als, a 3-basepair deletion causing the loss of Asn281 in exon 3 and a major deletion of exons 10-13 were present in the maternal and paternal mutant IR alleles, respectively. Prenatal diagnosis was made in each family by a specific approach combining denaturing gradient gel electrophoresis (DGGE) and Southern blotting. This methodology allowed us to correctly predict the genotype of the two fetuses at the IR locus.
authors.affiliation: Unité INSERM 402, Faculté de Médecine Saint-Antoine, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Desbois-Mouthon
authors.forename: E
authors.initials: E
authors.lastname: Girodon
authors.forename: N
authors.initials: N
authors.lastname: Ghanem
authors.forename: M
authors.initials: M
authors.lastname: Caron
authors.forename: A
authors.initials: A
authors.lastname: Pennerath
authors.forename: P
authors.initials: P
authors.lastname: Conteville
authors.forename: J
authors.initials: J
authors.lastname: Magre
authors.forename: C
authors.initials: C
authors.lastname: Besmond
authors.forename: M
authors.initials: M
authors.lastname: Goossens
authors.forename: J
authors.initials: J
authors.lastname: Capeau
authors.forename: S
authors.initials: S
authors.lastname: Amselem
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D005808:Genes, Recessive; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D007223:Infant; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D010375:Pedigree; D011237:Predictive Value of Tests; D011296:Prenatal Diagnosis; D011972:Receptor, Insulin / Q000235:genetics*; D013577:Syndrome
chemical_list: D011972:Receptor, Insulin