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

Single large mitochondrial DNA deletions (ΔmtDNA) are usually spontaneously occurring and cause a wide variety of symptoms, ranging from severe infantile multisystem disorders to adult onset progressive external ophthalmoplegia (PEO). There is always heteroplasmy with a mixture or normal and mutant mtDNA and the levels usually vary widely between tissues. There is at present insufficient scientific basis for accurate genetic counselling of women with ΔmtDNA, but it is reasonable to assume that ΔmtDNA can be transmitted if it is present in the female germ cells. Here, we present the results of prenatal analysis in a woman with ΔmtDNA and PEO. No ΔmtDNA 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 unlikely that the child will develop a severe infantile mitochondrial disorder due to transmission of high levels of ΔmtDNA. However, the complex mitochondrial genetics and the limited access to human tissues makes it impossible to exclude transmission of low levels of ΔmtDNA that possibly could cause disease later in life. Copyright (C) 2000 John Wiley and Sons, Ltd.