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De novo mutation in the mitochondrial tRNA Leu(UUR) gene (A3243G) with rapid segregation resulting in MELAS in the offspring
Author(s) -
Ko CH,
Lam CW,
Tse PWT,
Kong CK,
Chan AKH,
Wong LJC
Publication year - 2001
Publication title -
journal of paediatrics and child health
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.631
H-Index - 76
eISSN - 1440-1754
pISSN - 1034-4810
DOI - 10.1046/j.1440-1754.2001.00611.x
Subject(s) - heteroplasmy , lactic acidosis , melas syndrome , medicine , muscle biopsy , frameshift mutation , mitochondrial myopathy , buccal swab , nonsense mutation , mitochondrial dna , endocrinology , pathology , mutation , microbiology and biotechnology , biology , genetics , biopsy , missense mutation , gene
: A 14‐year‐old Chinese boy with a normal perinatal and early developmental history presented at 5 years of age with migraine, intractable epilepsy, ataxia, supraventricular tachycardia, paralytic ileus and progressive mental deterioration. Computerized tomography revealed multiple cerebral infarcts in the parieto‐occipital region without basal ganglial calcification. Magnetic resonance imaging showed increased signal intensity in T2 weighted images in the same regions. A cerebral digital subtraction angiogram was normal. Venous lactate, pyruvate, lactate to pyruvate ratio and cerebrospinal fluid lactate were elevated. Muscle biopsy did not reveal any ragged red fibres; dinucleotide–tetrazolium reductase activity was normal. Mitochondrial DNA analysis detected an adenine to guanine mutation at nucleotide position 3243 of tRNA Leu(UUR) . All four tissues analysed demonstrated heteroplasmy: leucocyte 56%, hair follicle 70%; buccal cell 64%; muscle 54%. The mother and brother of the proband, both asymptomatic, were also found to have a heteroplasmic A3243G mutation in the leucocytes, hair follicle and buccal cells. Other members of the maternal lineage, including the maternal grandmother, did not have the mutation. This report describes a patient with mitochondrial encephalopathy, lactic acidosis, stroke‐like episodes, who presented with multisystem involvement. The absence of ragged red fibres in muscle biopsy did not preclude the diagnosis. Mutational analysis of mitochodrial DNA conveniently confirmed the diagnosis of the disorder. A de novo mutaton is demonstrated in this family.