Risk of developing a mitochondrial DNA deletion disorder

被引:127
作者
Chinnery, PF [1 ]
DiMauro, S
Shanske, S
Schon, EA
Zeviani, M
Mariotti, C
Carrara, F
Lombes, A
Laforet, P
Ogier, H
Jaksch, M
Lochmüller, H
Horvath, R
Deschauer, M
Thorburn, DR
Bindoff, LA
Poulton, J
Taylor, RW
Matthews, JNS
Turnbull, DM
机构
[1] Newcastle Univ, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[2] Newcastle Univ, Sch Math & Stat, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[3] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA
[4] Columbia Univ Coll Phys & Surg, Dept Genet, New York, NY 10032 USA
[5] Columbia Univ Coll Phys & Surg, Dept Dev, New York, NY 10032 USA
[6] Natl Neurol Inst Carlo Besta, Pierfranco & Louisa Mariani Ctr Study Childrens M, Unit Mol Neurogenet, Milan, Italy
[7] Hop La Pitie Salpetriere, Paris, France
[8] Hop Robert Debre, F-75019 Paris, France
[9] Metab Dis Ctr Munich Schwabing, Munich, Germany
[10] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-8000 Munich, Germany
[11] Univ Halle Wittenberg, Dept Neurol, Halle An Der Saale, Germany
[12] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia
[13] Haukeland Hosp, Dept Neurol, N-5021 Bergen, Norway
[14] Univ Oxford, Dept Obstet & Gynaecol, Oxford, England
关键词
D O I
10.1016/S0140-6736(04)16851-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Pathogenic mitochondrial DNA (mtDNA) mutations are found in at least one in 8000 individuals. No effective treatment for mtDNA disorders is available, making disease prevention important. Many patients with mtDNA disease harbour a single pathogenic mtDNA deletion, but the risk factors for new cases and disease recurrence are not known. Methods We did a multicentre study of 226 families in which a single mtDNA deletion had been identified in the proband, including patients with chronic progressive external ophthalmoplegia, Kearns Sayre syndrome, or Pearson's syndrome. We studied the relation between maternal age and the risk of unaffected mothers having an affected child, and determined the recurrence risks among the siblings and offspring of affected individuals. Findings We noted no relation between maternal age and the risk of unaffected mothers having children with an mtDNA deletion disorder. None of the 251 siblings of the index cases developed clinical features of mtDNA disease. Risk of recurrence among the offspring of affected women was 4.11% (95% CI 0.86-11.54, or one in 117 to one in nine births). Only one of the mothers who had an affected child had a duplication of mtDNA in skeletal muscle. Interpretation Unlike nuclear chromosomal rearrangements, incidence of mtDNA deletion disorders does not increase with maternal age, and unaffected mothers are unlikely to have more than one affected child. Affected women were previously thought to have a negligible chance of having clinically affected offspring, but the actual risk is, on average, about one in 24 births.
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页码:592 / 596
页数:5
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