Diabetes mellitus is one of the heterogeneous phenotypic features of a mitochondrial DNA point mutation within the tRNA<sup>Leu(UUR)</sup> gene

Gerbitz, Klaus-Dieter; Paprotta, A.; Jaksch, Michaela; Zierz, Stephan; Drechsel, J.

doi:10.1016/0014-5793(93)80106-5

Cited by 55 publications

(20 citation statements)

References 10 publications

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“…The phenotypic expression in individuals with deletions and mutations in mitochondrial DNA is highly variable, but includes various combinations of diabetes mellitus [Gerbitz et al, 1993;Goto et al, 1991;Moares et al, 1989;Pilz et al, 1994], hypoparathyroidism [Zupanc et al, 1991], retinal degeneration [Howell et al, 1991;Huoponen et al, 1991;Johns and Smith et al, 1993;Johns and Heher et al, 1993], deafness [Gerbitz et al, 1993;Goto et al, 1991;Moares et al, 1989;Pilz et al, 1989], renal disease [Majander et al, 1991;Superti-Furga et al, 1993;Venkataraman et al, 1987;Zupanc et al, 1991], and mental retardation [Newman et al, 1991;Tatuch et al, 1992]. Accordingly, we isolated DNA and looked for deletions and mutations of the mitochondrial genome.…”

Section: Methods and Resultsmentioning

confidence: 99%

Multiple endocrinopathies in an infant with fatal neurodegenerative disease

et al. 1997

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We report on a male infant with congenital hypoparathyroidism who developed primary hypothyroidism at 3 months and insulin-dependent diabetes mellitus at 25 months. He had evidence of widespread and progressive neurologic dysfunction characterized by severe developmental delay, blindness, deafness, seizures, atrophy of the cerebellar and frontal lobes, and elevated spinal fluid protein. Also noted were renal hypoplasia, hyporeninemic hypoaldosteronism, chronic anemia, persistent elevation of liver transaminase levels, abnormal intraventricular cardiac conduction, reduction in numbers of helper T-cells, and distinctive facial anomalies. The child died of multiorgan failure at 29 months. A mitochondrial basis for the syndrome was considered but a molecular mechanism has, as yet, not been identified.

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Section: Methods and Resultsmentioning

confidence: 99%

Multiple endocrinopathies in an infant with fatal neurodegenerative disease

et al. 1997

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“…The reason for the different results may be in the selection of patients, the difference in races, the use of different methods, and the degree of heteroplasmy. The degree of heteroplasmy reported differs in various tissues and in various subjects (15,16,26). Larsson et al (25) reported that Ͼ92% of mtDNA with the tRNA Lys 8344 mutation in muscle is needed to cause respiratory chain dysfunction detected by biochemical methods, and the levels of mutated mtDNA in lymphocytes were 12.0 to 27.6% of those in muscle.…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode [A to G transition mutation in the mitochondrial transfer RNA Leu (tRNA Leu ) gene at position 3243] (14,15), myoclonic epilepsy with ragged red fiber (A to G transition mutation in the mitochondrial tRNA Lys gene at position 8344) (16), and other mitochondrial cytopathies are associated with diabetes mellitus. The above observations suggest that alterations of mitochondrial DNA (mtDNA) may to some degree contribute to the development of diabetes mellitus.…”

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confidence: 99%

Mitochondrial Gene Transfer Ribonucleic Acid (tRNA)^Leu(UUR)3243 and tRNA^Lys8344 Mutations and Diabetes Mellitus in Korea

Song

Park

et al. 1997

The Journal of Clinical Endocrinology & Metabolism

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The high prevalence of diabetic patients with a mutation in the mitochondrial gene (the 3243 and 8344 bp mutations) has been identified in Japan. To determine the prevalence of diabetic patients with those mutations in Korea, we randomly screened selected 503 clinical diabetic patients regardless of their diabetes types. We found only 1 patient with the mitochondrial DNA mutation at position 3243 (percent mutation, 32%), and the mitochondrial DNA mutation at position 8344 was not found in any of the patients. The affected subject was a 22-yr-old man with a history of myoclonic epilepsy and mild sensorineural hearing loss, a 1-yr duration of diabetes mellitus, and a low level C peptide response to oral glucose. Because of the low frequency of these mutations in the Korean diabetic population, we concluded that these particular mutations of mitochondrial DNA may not be a common contributor to diabetes mellitus in Korea. (J Clin Endocrinol Metab 82: 372-374, 1997)

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“…This substitution cosegregated with diabetes mellitus and deafness (6,(14)(15)(16)(17)(18)(19) and other clinical manifestations including cardiomyopathy (20) and MELAS (10,21,22). In agreement with a mitochondrial gene mutation, these phenotypes appear to be maternally inherited as shown in Families 1, 3 and 4.…”

Section: Discussionmentioning

confidence: 99%

Clinical Manifestations due to a Point Mutation of the Mitochondrial tRNAleu(UUR) Ge Five Families with Diabetes Mellitus.

et al. 1998

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It has been shown that an adenine (A) to guanine (G) transition at position 3243 of the mitochondrial transfer RNA(tRNA)leu(UUR) gene is associated with a subgroup of diabetes mellitus. Therefore, we screened for this transition in 86 patients with non-insulin-dependent diabetes mellitus (NIDDM)in which two or three generations were affected with diabetes, in 14 patients with insulin-dependent diabetes mellitus, and in 9 families with diabetes mellitus and/or associated disorders suggesting mitochondrial gene abnormalities. Wefailed to identify the mutation in 100 diabetic patients, 86 NIDDMand 14 insulin-dependent diabetes mellitus (IDDM). Out of the latter 9 families, we identified an A to G transition in 14 individuals in 5 families. Diabetes mellitus was shown to be maternally inherited in one family. In 9 of 14 patients with the mutation, insulin was required to treat diabetes mellitus, indicating impaired insulin secretion. A hyperglycemic clamp test performed in one subject revealed significant impairment of insulin secretion, whereas euglycemic clamp test showed normal insulin sensitivity in this patient. The heteroplasmy of the mutant mitochondrial DNA(mtDNA)in leukocytes does not appear to correlate with the severity of diabetes in terms of the insulin therapy required. Bodymass index of the affected individuals was less than 23.3. In one family, in addition to diabetes mellitus and hearing loss, hypoparathyroidism was associated with the mutation, suggesting that hypoparathyroidism is caused by the impaired processing and/or secretion of proparathyroid hormone due to the mutation. In addition, the affected subjects presented with proteinuria at the time of diagnosis of diabetes mellitus which appeared not to be related with diabetic nephropathy. (Internal Medicine 37: 265-272, 1998)

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Diabetes mellitus is one of the heterogeneous phenotypic features of a mitochondrial DNA point mutation within the tRNA^Leu(UUR) gene

Abstract: A heteroplasmic point mutation (transition A-to-G at nucleotide position 3,243 in the mitochondrial tRNALe"(""a) gene) is found in a family suffering from a syndrome with diabetes, deafness and cardiomyopathy as the predominant clinical features.

Cited by 55 publications

References 10 publications

Multiple endocrinopathies in an infant with fatal neurodegenerative disease

Multiple endocrinopathies in an infant with fatal neurodegenerative disease

Mitochondrial Gene Transfer Ribonucleic Acid (tRNA)^Leu(UUR)3243 and tRNA^Lys8344 Mutations and Diabetes Mellitus in Korea

Clinical Manifestations due to a Point Mutation of the Mitochondrial tRNAleu(UUR) Ge Five Families with Diabetes Mellitus.

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Diabetes mellitus is one of the heterogeneous phenotypic features of a mitochondrial DNA point mutation within the tRNALeu(UUR) gene

Abstract: A heteroplasmic point mutation (transition A-to-G at nucleotide position 3,243 in the mitochondrial tRNALe"(""a) gene) is found in a family suffering from a syndrome with diabetes, deafness and cardiomyopathy as the predominant clinical features.

Cited by 55 publications

References 10 publications

Multiple endocrinopathies in an infant with fatal neurodegenerative disease

Multiple endocrinopathies in an infant with fatal neurodegenerative disease

Mitochondrial Gene Transfer Ribonucleic Acid (tRNA)Leu(UUR)3243 and tRNALys8344 Mutations and Diabetes Mellitus in Korea

Clinical Manifestations due to a Point Mutation of the Mitochondrial tRNAleu(UUR) Ge Five Families with Diabetes Mellitus.

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Diabetes mellitus is one of the heterogeneous phenotypic features of a mitochondrial DNA point mutation within the tRNA^Leu(UUR) gene

Mitochondrial Gene Transfer Ribonucleic Acid (tRNA)^Leu(UUR)3243 and tRNA^Lys8344 Mutations and Diabetes Mellitus in Korea