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 deficiency (GHRD) is an autosomal recessive condition characterized by severe growth failure. Diverse alterations in the GHR gene have been reported in affected individuals. We report here the first family with GHRD from Russia, with two affected siblings and consanguineous parents. Analysis of blood spot DNA by polymerase chain reaction (PCR), denaturing gradiant gel electrophoresis, and nucleotide sequencing indicated that these siblings are homozygous for a nonsense mutation, R43X, in the GHR gene. The R43X mutation, which changes an arginine codon to a translational stop codon, occurs at a CpG dinucleotide mutational hotspot and has previously been identified in affected individuals of Mediterranean and Ecuadorian origin.
Rosenbloom
A L
AL
Department of Pediatrics, University of Florida, Gainesville, USA.
Berg
M A
MA
Kasatkina
E P
EP
Volkova
T N
TN
Skorobogatova
V F
VF
Sokolovskaya
V N
VN
Francke
U
U
D001483:Base Sequence; D002675:Child, Preschool; D018389:Codon, Nonsense; D005808:Genes, Recessive / Q000235:genetics; D006130:Growth Disorders / Q000235:genetics* / Q000503:physiopathology; D013006:Growth Hormone / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D014176:Protein Biosynthesis; D011986:Receptors, Somatotropin / Q000235:genetics*; D012426:Russia; D013577:Syndrome
D018389:Codon, Nonsense; D011986:Receptors, Somatotropin; D013006:Growth Hormone