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SURF1 ‐associated leigh syndrome: A case series and novel mutations
Author(s) -
Lee InnChi,
ElHattab Ayman W.,
Wang Jing,
Li FangYuan,
Weng ShaoWen,
Craigen William J.,
Wong LeeJun C.
Publication year - 2012
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22095
Subject(s) - biology , frameshift mutation , genetics , missense mutation , nonsense mutation , leigh disease , mitochondrial disease , exon , mutation , gene , mitochondrial dna
Abstract Leigh syndrome (LS) is a mitochondrial disease that typically presents in infancy with subacute neurodegenerative encephalopathy. It is genetically heterogeneous, but mutations in the complex IV assembly genes, particularly SURF1 , are an important cause. In this study, SURF1 gene was sequenced in 590 patients with clinical suspicion of LS, complex IV deficiency, or clinical features of mitochondrial disorders. We identified 21 patients with clinical features of LS who are either homozygous or compound heterozygous for SURF1 mutations. Twenty‐two different mutations were identified, including 13 novel mutations. Of the 42 mutant alleles, 36 (86%) are null mutations (frameshift, splicing, or nonsense) and 6 (14%) are missense. We have also reviewed the previously reported SURF1 mutations and observed a clustering of mutation in exon 8 of SURF1 , suggesting a vital function for this region. Although mutations in SURF1 have been mainly associated with typical LS, five of the patients in this report had an atypical course of LS. There is no definite genotype–phenotype correlation; however, frameshift mutations resulting in protein truncation closer to the C‐terminus may carry a better prognosis. Hum Mutat 33:1192–1200, 2012. © 2012 Wiley Periodicals, Inc.