SURF1 missense mutations promote a mild Leigh phenotype

Abstract

(i) The presence of a missense mutation in the SURF1 gene may correlate with a milder course and longer survival of Leigh patients, (ii) normal magnetic resonance imaging (MRI) findings, normal blood lactate value, and only mild decrease of cytochrome c oxidase (COX) activity are not sufficient reasons to forego SURF1 mutation analysis in differential diagnosis.

A guide to diagnosis and treatment of Leigh syndrome

“…This is illustrated by a report about a consanguineous family where exome sequencing identified mutations in NDUFS8 , causing a rather mild, slowly progressive phenotype in older children 62. Moreover, SURF1 missense mutations may promote a late-onset LS phenotype 63. It is expected that a broader use of untargeted genetic methods (eg, whole exome analysis) will uncover novel mutations and molecular mechanisms, possibly rewriting the clinical spectrum of LS patients.…”

Analysis of Leigh Syndrome Mutations in the Yeast SURF1 Homolog Reveals a New Member of the Cytochrome Oxidase Assembly Factor Family

“…Missense mutations in SURF1 are very rare, with only a limited number being reported (28). We selected three known missense mutations in SURF1 LS patients that result in G 124 E, I 246 T, and Y 274 D substitutions in SURF1 (31,39).…”

“…Missense mutations in SURF1 are quite rare, with only a limited number being reported. These mutations tend to be associated with a mild clinical phenotype, and patient survival is prolonged (28). We selected a subset of known missense mutations, two of which lie within the IMS globular domain and a third that maps to the second TM domain.…”

Identification of a novel deletion in SURF1 gene: Heterogeneity in Leigh syndrome with COX deficiency

“…Several inborn errors of energy metabolism, such as pyruvate dehydrogenase and mitochondrial respiratory chain (MRC) deficiencies have been associated with LS, although in some cases the cause cannot be identified. One of the most common enzymatic deficiencies associated to LS is cytochrome c oxidase (COX, complex IV) dysfunction (Piekutowska-Abramczuk et al, 2009).…”

“…The SURF1 gene is located at chromosome 9p34, in a cluster referred as the "surfeit" genes that are highly conserved throughout evolution (Duhig et al, 1998). It encodes a mitochondrial inner membrane protein with 300 amino acids (Piekutowska-Abramczuk et al, 2009) that is involved in the assembly and maintenance of complex IV (Kovárová et al, 2012).…”