The expanding clinical phenotype of the tRNA{sup Leu(UUR)} A{r_arrow}G mutation at np 3243 of mitochondrial DNA: Diabetic embryopathy associated with mitochondrial cytopathy

Journal Article · Wed Apr 24 04:00:00 EDT 1996 · American Journal of Medical Genetics

DOI:https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4<404::AID-AJMG14>3.0.CO;2-S· OSTI ID:391076

Feigenbaum, A; Chitayat, D; Robinson, B; MacGregor, D; Myint, T ^[1]

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1. Univ. of Toronto, Ontario (Canada); and others

We describe a family which demonstrates and expands the extreme clinical variability now known to be associated with the A{r_arrow}G transition at nucleotide position 3243 of the mitochondrial DNA. The propositus presented at birth with clinical manifestations consistent with diabetic embryopathy including anal atresia, caudal dysgenesis, and multicystic dysplastic kidneys. His co-twin was normal at birth, but at 3 months of life, presented with intractable seizures later associated with developmental delay. The twins` mother developed diabetes mellitus type I at the age of 20 years and gastrointestinal problems at 22 years. Since age 19 years, the maternal aunt has had recurrent strokes, seizures, mental deterioration and deafness, later diagnosed as MELAS syndrome due to the tRNA{sup Leu(UUR)} A{r_arrow}G mutation. A maternal uncle had diabetes mellitus type I, deafness, and normal intellect, and died at 35 years after recurrent strokes. This pedigree expands the known clinical phenotype associated with tRNA{sup Leu(UUR)} A{r_arrow}G mutation and raises the possibility that, in some cases, diabetic embryopathy may be due to a mitochondrial cytopathy that affects both the mother`s pancreas (and results in diabetes mellitus and the metabolic dysfunction associated with it) and the embryonic/fetal and placental tissues which make the embryo more vulnerable to this insult. 33 refs., 1 tab.

• OSTI ID: 391076
• Journal Information: American Journal of Medical Genetics, Journal Name: American Journal of Medical Genetics Journal Issue: 4 Vol. 62; ISSN 0148-7299; ISSN AJMGDA
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
AMINO ACIDS
CONGENITAL DISEASES
DIABETES MELLITUS
GENETICS
HEREDITARY DISEASES
MITOCHONDRIA
MUTATIONS
NUCLEOTIDES
PATIENTS
PHENOTYPE
POLYMERASE CHAIN REACTION
TRANSFER RNA