Progress in genetic counselling and prenatal diagnosis of maternally inherited mtDNA diseases

Mitochondrial DNA is almost entirely maternally inherited. Thousands of cop ies of mitochondrial DNA are present in every nucleated cell and in most no rmal individuals these are virtually identical (homoplasmy). Mitochondrial DNA diseases may be caused by mutations in either mitochondrial (Nature 198 8;331:717-719) or nuclear genes (Nature 1989;339(6222):309-311; Br J Hosp M ed 1996;55:712-716) and hence give rise to maternal or autosomal patterns o f inheritance. Antenatal diagnosis of mitochondrial diseases based on chori onic villus sampling is available for Mendelian disorders and the syndromes caused by mutations at bp 8993 (associated with both Leigh's syndrome or n eurogenic weakness ataxia and retinitis pigmentosa). However, prenatal diag nosis of many other maternally inherited mitochondrial DNA diseases is less reliable because it is not possible to predict the way in which heteroplas mic mitochondrial DNA mutations segregate within tissues with confidence. T his review focuses on the substantial progress that ha?, been made recently , anti on the applicability of prenatal diagnosis to genetic counselling in this field. (C) 2000 Elsevier Science B.V. All rights reserved.