Complex genetic counselling and prenatal analysis in a woman with externalophthalmoplegia and deleted mtDNA

Single large mitochondrial DNA deletions (Delta mtDNA) are usually spontane ously occurring and cause a wide variety of symptoms, ranging from severe i nfantile multisystem disorders to adult onset progressive external ophthalm oplegia (PEO). There is always heteroplasmy with a mixture of normal and mu tant mtDNA and the levels usually vary widely between tissues. There is at present insufficient scientific basis for accurate genetic counselling of w omen with Delta mtDNA, but it is reasonable to assume that Delta mtDNA can be transmitted if it is present in the female germ cells. Here, we present the results of prenatal analysis in a woman with Delta mtDNA and PEO. No De lta mtDNA was detected by Southern blot and PCR analyses of chorionic villi from the first trimester of pregnancy, in cord blood obtained at birth or in peripheral blood from the child at six months of age. This makes it unli kely that the child will develop a severe infantile mitochondrial disorder due to transmission of high levels of Delta mtDNA. However, the complex mit ochondrial genetics and the limited access to human tissues makes it imposs ible to exclude transmission of low levels of Delta mtDNA that possibly cou ld cause disease later in life. Copyright (C) 2000 John Wiley & Sons, Ltd.