title: Complex genetic counselling and prenatal analysis in a woman with external ophthalmoplegia and deleted mtDNA.
abstract: Single large mitochondrial DNA deletions (DeltamtDNA) 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 of 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 DeltamtDNA, but it is reasonable to assume that DeltamtDNA can be transmitted if it is present in the female germ cells. Here, we present the results of prenatal analysis in a woman with DeltamtDNA and PEO. No DeltamtDNA 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 DeltamtDNA. However, the complex mitochondrial genetics and the limited access to human tissues makes it impossible to exclude transmission of low levels of DeltamtDNA that possibly could cause disease later in life.
authors.affiliation: Department of Molecular Medicine, Karolinska Institutet, Clinical Genetics Unit, Karolinska Hospital, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Graff
authors.forename: A
authors.initials: A
authors.lastname: Wredenberg
authors.forename: J P
authors.initials: JP
authors.lastname: Silva
authors.forename: T H
authors.initials: TH
authors.lastname: Bui
authors.forename: K
authors.initials: K
authors.lastname: Borg
authors.forename: N G
authors.initials: NG
authors.lastname: Larsson
mesh_terms: D000328:Adult; D001706:Biopsy; D015139:Blotting, Southern; D015193:Chorionic Villi Sampling; D004272:DNA, Mitochondrial / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005817:Genetic Counseling; D006801:Humans; D009132:Muscles / Q000473:pathology; D009886:Ophthalmoplegia / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011256:Pregnancy Outcome; D011296:Prenatal Diagnosis
chemical_list: D004272:DNA, Mitochondrial; C025630:CAGCTG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific