Screening of patients with maternally transmitted diabetes for mitochondrial gene mutations in the tRNA[Leu(UUR)] region

• Published in: Diabetic medicine Vol. 14; no. 12; pp. 1032 - 1037
• Main Authors: Tsukuda, K, Suzuki, Y, Kameoka, K, Osawa, N, Goto, Y, Katagiri, H, Asano, T, Yazaki, Y, Oka, Y
• Format: Journal Article
• Language: English
• Published: England 01.12.1997
• Subjects: Adult; Base Sequence; Diabetes Mellitus - classification; Diabetes Mellitus - genetics; DNA Primers - chemistry; DNA, Mitochondrial - genetics; Female; Humans; Male; Middle Aged; Mothers; Point Mutation - genetics; Polymerase Chain Reaction; RNA, Transfer, Leu - genetics
• ISSN: 0742-3071
• DOI: 10.1002/(SICI)1096-9136(199712)14:12<1032::AID-DIA504>3.0.CO;2-Y

To investigate the prevalence and clinical characteristics of diabetes mellitus caused by mitochondrial gene mutations in the tRNA[Leu(UUR)] region, a known 'hot spot' for pathogenic mutations, we screened 440 diabetic patients with diabetic mothers for 11 mitochondrial gene mutations reported in mitochondrial neuromuscular disorders; nucleotide pairs (np) 3250, 3251, 3252, 3254, 3256, 3260, 3271, 3291, 3302 and 3303 in addition to an A to G transition at np 3243. The dot-blot hybridization method using 32P-labelled sequence-specific oligonucleotides as probes was used. One subject carrying a T to C transition at np 3271 and seven carrying the A to G transition at np 3243 were identified, while none of the other diabetic patients screened had these mutations in the tRNA[Leu(UUR)] region. The patient with the 3271 mutation, a 39-year-old male, had excellent glycaemic control with diet alone and had neither hearing impairment nor symptoms suggesting mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Thus, among patients with maternally transmitted diabetes, the prevalence of the 3271 mutation was approximately one-seventh that of the 3243 mutation, and other mutations are even more rare in the mitochondrial tRNA[Leu(UUR)] region.