Identification of novel C253Y missense and Y864X nonsense mutations in the insulin receptor gene in type A insulin-resistant patients.
Mutations in the insulin receptor gene have been reported in cases of type A insulin resistance. We report herein two cases of type A insulin resistance, which involve some novel mutations. Case 1 is a heterozygote of the C253Y missense mutation and case 2 is a heterozygote of the Y864X nonsense mutation. In the C253Y missense mutation in exon 3, a cysteine residue is replaced with tyrosine in the cysteine-rich domain of the alpha subunit. The Y864X in exon 13 results in a truncated receptor, which is devoid of most of the beta subunit. This mutant receptor could not be expressed on a cell membrane since the transmembrane domain is missing. Other significant mutations were not found for the entire coding regions and splice/donor sites.
Osawa
H
H
Department of Laboratory Medicine, Kitamuro Clinic, Department of Pediatrics, Ehime University School of Medicine, Ehime, Japan. harosawa@m.ehime-u.ac.jp
Nishimiya
T
T
Ochi
M
M
Niiya
T
T
Onuma
H
H
Kitamuro
F
F
Kaino
Y
Y
Kida
K
K
Makino
H
H
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D003062:Codon / Q000235:genetics; D018389:Codon, Nonsense; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D011972:Receptor, Insulin / Q000235:genetics*; D017422:Sequence Analysis, DNA
D003062:Codon; D018389:Codon, Nonsense; D011972:Receptor, Insulin