<abstract xmlns="http://www.w3.org/1999/xhtml"><bold>Objectives.</bold> 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 <italic>SURF1</italic> encodes an assembly factor for cytochrome c-oxidase complex of the respiratory chain and autosomal recessive mutations in <italic>SURF1</italic> 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.<bold>Methods and results.</bold> 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, <italic>SURF1</italic> was screened by Sanger sequencing. Four different heterozygous mutations were identified in <italic>SURF1</italic>: c.312_321delinsAT:p.(Pro104Profs*1), c.588+1G>A, c.823_833+7del:p. (?) and c.845_846del:p.(Ser282Cysfs*9). All the mutations are predicted to have a loss-of-function effect.<bold>Conclusions.</bold> We identified disease-causing mutations in all three probands, which points to the important role of <italic>SURF1</italic> 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 <italic>SURF1</italic> gene seems to be an effective method of DNA analysis.</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.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_321delinsAT:p.(Pro104Profs*1), c.588+1G>A, c.823_833+7del:p. (?) and c.845_846del:p.(Ser282Cysfs*9). All the mutations are predicted to have a loss-of-function effect.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.

Mutations in <italic>SURF1</italic> are important genetic causes of Leigh syndrome in Slovak patients

Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences

Department of Paediatrics, Medical Faculty

Department of Pediatric Neurology, Medical Faculty

Endocrine Regulations

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Mutations in  are important genetic causes of Leigh syndrome in Slovak patients

Objectives. Leigh syndrome is a progressive early onset neurodegenerative disease typically presenting with psychomotor regression, signs of brainstem and/or...

Mutations in SURF1 are important genetic causes of Leigh syndrome in Slovak patients

Publié en ligne: 30 avr. 2018

Pages: 110 - 118

DOI: https://doi.org/10.2478/enr-2018-0013

Mots clés
Leigh syndrome, mitochondrial disease, SURF1, whole exome sequencing

© 2018 Daniel Danis et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Mutations in SURF1 are important genetic causes of Leigh syndrome in Slovak patients

Publié en ligne: 30 avr. 2018

Pages: 110 - 118

DOI: https://doi.org/10.2478/enr-2018-0013

Mots clésLeigh syndrome, mitochondrial disease, SURF1, whole exome sequencing

© 2018 Daniel Danis et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Mots clés
Leigh syndrome, mitochondrial disease, SURF1, whole exome sequencing