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Sporadic intragenic inversion of the mitochondrial DNA MTND1 gene causing fatal infantile lactic acidosis

Lookup NU author(s): Dr Kate Rennie, Dr Matthias Elstner, Professor Zofia Chrzanowska-LightowlersORCiD, Emeritus Professor Doug Turnbull, Professor Robert Taylor


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Mutations of mitochondrial DNA (mtDNA) are an important cause of genetic disease, yet rarely present in the neonatal period. Here we report the clinical, biochemical, and molecular genetic findings of an infant who died at the age of 1 mo with marked biventricular hypertrophy, aortic coarctation, and severe lactic acidosis due to a previously described but unusual mtDNA mutation, a 7-bp intragenic inversion within the mitochondrial gene encoding ND1 protein of complex I (MTND1). In direct contrast to the previous case, an adult with exercise intolerance who only harbored the mutation in muscle, the MTND1 inversion in our patient was present at high levels in several tissues including the heart, muscle, liver, and cultured skin fibroblasts. There was no evidence of the mutation or respiratory complex I defect in a muscle biopsy from the patient's mother. Transmitochondrial cytoplasmic hybrids (cybrids) containing high mutant loads of the inversion expressed the biochemical defect but apparently normal levels of the assembled complex. Our report highlights the enormous phenotypic diversity that exists among pathogenic mtDNA mutations and reemphasizes the need for appropriate genetic counseling for families affected by mtDNA disease. Copyright © 2006 International Pediatric Research Foundation, Inc.

Publication metadata

Author(s): Blakely EL, Rennie KJ, Jones L, Elstner M, Chrzanowska-Lightowlers ZMA, White CB, Shield JPH, Pilz DT, Turnbull DM, Poulton J, Taylor RW

Publication type: Article

Publication status: Published

Journal: Pediatric Research

Year: 2006

Volume: 59

Issue: 3

Pages: 440-444

ISSN (print): 0031-3998

ISSN (electronic): 1530-0447

Publisher: Lippincott Williams & Wilkins


DOI: 10.1203/01.pdr.0000198771.78290.c4

PubMed id: 16492986


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Funder referenceFunder name
Wellcome Trust
074454Wellcome Trust