Genomic deletions in OPA1 in Danish patients with autosomal dominant optic atrophy

BMC Medical Genetics

Research Article

Gitte J Almind¹  Karen Grønskov¹  Jakob Ek²  Michael Larsen³  Karen Brøndum-Nielsen⁴  Dan Milea⁵ 

[1] Center for Applied Human Molecular Genetics, The Kennedy Center, Glostrup, Denmark;Center for Applied Human Molecular Genetics, The Kennedy Center, Glostrup, Denmark;Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark;Center for Applied Human Molecular Genetics, The Kennedy Center, Glostrup, Denmark;Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark;Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;Center for Applied Human Molecular Genetics, The Kennedy Center, Glostrup, Denmark;Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;Ophthalmology Department, Angers University Hospital, Angers, France;Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark;

关键词: Retinal Nerve Fiber Layer;    Segregation Analysis;    Genomic Rearrangement;    Index Patient;    Genomic Deletion;   

DOI  :  10.1186/1471-2350-12-49

 received in 2010-02-03, accepted in 2011-04-04,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundAutosomal dominant optic atrophy (ADOA, Kjer disease, MIM #165500) is the most common form of hereditary optic neuropathy. Mutations in OPA1 located at chromosome 3q28 are the predominant cause for ADOA explaining between 32 and 89% of cases. Although deletions of OPA1 were recently reported in ADOA, the frequency of OPA1 genomic rearrangements in Denmark, where ADOA has a high prevalence, is unknown. The aim of the study was to identify copy number variations in OPA1 in Danish ADOA patients.MethodsForty unrelated ADOA patients, selected from a group of 100 ADOA patients as being negative for OPA1 point mutations, were tested for genomic rearrangements in OPA1 by multiplex ligation probe amplification (MLPA). When only one probe was abnormal results were confirmed by additional manually added probes. Segregation analysis was performed in families with detected mutations when possible.ResultsTen families had OPA1 deletions, including two with deletions of the entire coding region and eight with intragenic deletions. Segregation analysis was possible in five families, and showed that the deletions segregated with the disease.ConclusionDeletions in the OPA1 gene were found in 10 patients presenting with phenotypic autosomal dominant optic neuropathy. Genetic testing for deletions in OPA1 should be offered for patients with clinically diagnosed ADOA and no OPA1 mutations detected by DNA sequencing analysis.

【 授权许可】

CC BY   
© Almind et al; licensee BioMed Central Ltd. 2011