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Mutations in SURF1 are important genetic causes of Leigh syndrome in Slovak patients.
- Source :
-
Endocrine regulations [Endocr Regul] 2018 Apr 01; Vol. 52 (2), pp. 110-118. - Publication Year :
- 2018
-
Abstract
- Objectives: Leigh syndrome is a progressive early onset neurodegenerative disease typically presenting with psychomotor regression, signs of brainstem and/or basal ganglia disease, lactic acidosis, and characteristic magnetic resonance imaging findings. At molecular level, deficiency of respiratory complexes and/or pyruvate dehydrogenase complex is usually observed. Nuclear gene SURF1 encodes an assembly factor for cytochrome c-oxidase complex of the respiratory chain and autosomal recessive mutations in SURF1 are one of the most frequent causes of cytochrome c-oxidase-related Leigh syndrome cases. Here, we aimed to elucidate the genetic basis of Leigh syndrome in three Slovak families.<br />Methods and Results: Three probands presenting with Leigh syndrome were selected for DNA analysis. The first proband, presenting with atypical LS onset without abnormal basal ganglia magnetic resonance imaging findings, was analyzed with whole exome sequencing. In the two remaining probands, SURF1 was screened by Sanger sequencing. Four different heterozygous mutations were identified in SURF1: c.312&#95;321delinsAT:p.(Pro104Profs*1), c.588+1G>A, c.823&#95;833+7del:p. (?) and c.845&#95;846del:p.(Ser282Cysfs*9). All the mutations are predicted to have a loss-of-function effect.<br />Conclusions: We identified disease-causing mutations in all three probands, which points to the important role of SURF1 gene in etiology of Leigh syndrome in Slovakia. Our data showed that patients with atypical Leigh syndrome phenotype without lesions in basal ganglia may benefit from the whole exome sequencing method. In the case of probands presenting the typical phenotype, Sanger sequencing of the SURF1 gene seems to be an effective method of DNA analysis.
- Subjects :
- Child
Child, Preschool
Female
Humans
Infant
Leigh Disease diagnostic imaging
Leigh Disease pathology
Leigh Disease physiopathology
Male
Membrane Proteins antagonists & inhibitors
Mitochondrial Proteins antagonists & inhibitors
Mutation
Pedigree
Slovakia
Exome Sequencing
Leigh Disease genetics
Membrane Proteins genetics
Mitochondrial Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1210-0668
- Volume :
- 52
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Endocrine regulations
- Publication Type :
- Academic Journal
- Accession number :
- 29715184
- Full Text :
- https://doi.org/10.2478/enr-2018-0013