Maternal Segmental Disomy in Leigh Syndrome with Cytochrome c Oxidase Deficiency Caused by Homozygous SURF1 Mutation

A. K. J. van Riesen; H. Antonicka; A. Ohlenbusch; E. A. Shoubridge; E. K. G. Wilichowski

doi:10.1055/s-2006-924227

Neuropediatrics, Table of Contents

Neuropediatrics 2006; 37(2): 88-94
DOI: 10.1055/s-2006-924227

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Maternal Segmental Disomy in Leigh Syndrome with Cytochrome c Oxidase Deficiency Caused by Homozygous SURF1 Mutation

A. K. J. van Riesen¹ , H. Antonicka² , A. Ohlenbusch¹ , E. A. Shoubridge³ , E. K. G. Wilichowski¹

¹Department of Pediatrics and Pediatric Neurology, Georg August University Goettingen, Goettingen, Germany
²Montreal Neurological Institute, McGill University, Montreal, Québec, Canada
³Montreal Neurological Institute and Department of Human Genetics, McGill University, Montreal, Québec, Canada

Abstract

Cytochrome c oxidase deficiency (COX) is the most frequent cause of Leigh syndrome (LS), a mitochondrial subacute necrotizing encephalomyelopathy. Most of these LS^COX- patients show mutations in SURF1 on chromosome 9 (9q34), which encodes a protein essential for the assembly of the COX complex. We describe a family whose first-born boy developed characteristic features of LS. Severe COX deficiency in muscle was caused by a novel homozygous nonsense mutation in SURF1. Segregation analysis of this mutation in the family was incompatible with autosomal recessive inheritence but consistent with a maternal disomy. Haplotype analysis of microsatellite markers confirmed isodisomy involving nearly the complete long arm of chromosome 9 (9q21-9tel). No additional physical abnormalities were present in the boy, suggesting that there are no imprinted genes on the long arm of chromosome 9 which are crucial for developmental processes. This case of segmental isodisomy illustrates that genotyping of parents is crucial for correct genetic counseling.

Key words

Leigh syndrome - Cytochrome c oxidase deficiency - COX - SURF1 - maternal segmental disomy

Full Text

References

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Anne K. J. van Riesen

Department of Pediatrics and Pediatric Neurology
Georg August University Goettingen

Robert-Koch-Strasse 40

37075 Goettingen

Germany

Email: anne.van.riesen@web.de