SEVERE GROWTH-HORMONE INSENSITIVITY (LARON SYNDROME) DUE TO NONSENSE MUTATION OF THE GH RECEPTOR IN BROTHERS FROM RUSSIA

Primary GH insensitivity (Laron syndrome) due to GH receptor deficienc y (GHRD) is an autosomal recessive condition characterized by severe g rowth failure, Diverse alterations in the GHR gene have been reported in affected individuals. We report here the first family with GHRD fro m Russia, with two affected siblings and consanguineous parents, Analy sis of blood spot DNA by polymerase chain reaction (PCR), denaturing g radiant gel electrophoresis, and nucleotide sequencing indicated that these siblings are homozygous for a nonsense mutation, R43X, in the GH R gene. The R43X mutation, which changes an arginine codon to a transl ational stop codon, occurs at dinucleotide mutational hotspot and prev iously been identified in affected individuals of Mediterranean and Ec uadorian origin.