Premium
Novel SCO2 mutation (G1521A) presenting as a spinal muscular atrophy type I phenotype
Author(s) -
Tarnopolsky Mark A.,
Bourgeois J.M.,
Fu MH.,
Kataeva G.,
Shah J.,
Simon D.K.,
Mahoney D.,
Johns D.,
MacKay N.,
Robinson B.H.
Publication year - 2003
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.20466
Subject(s) - spinal muscular atrophy , lactic acidosis , compound heterozygosity , cytochrome c oxidase , sma* , biology , exon , muscle biopsy , hypotonia , pathology , mutation , microbiology and biotechnology , medicine , endocrinology , genetics , gene , biopsy , mitochondrion , mathematics , combinatorics
Abstract Rare cases of suspected spinal muscular atrophy (SMA) have been found to have cytochrome c oxidase (COX) deficiency. To date, four cases with SMA features have been reported in children with mutations in the synthesis of cytochrome oxidase 2 ( SCO2 ) gene. We report a male neonate who was born hypotonic, with persistent lactic acidosis, spontaneous activity with EMG testing, development of respiratory distress in the first few hours of life, and died at 30 days of age with progressive cardiomyopathy. Testing for survival motor neurone (smn) and NAIP deletions were negative and a skeletal muscle biopsy showed neurogenic features with severe reductions of COX enzymatic and histochemical staining intensity. Post‐mortem muscle, heart, and liver biopsies showed severe, moderate, and mild reductions in COX activity, respectively, with parallel findings in the protein content for the mitochondrial DNA (COII) and nuclear DNA (COIV) encoded subunits. DNA sequencing of exon 2 of the SCO2 gene revealed compound heterozygosity with mutations at G1541A (common mutation, E140K) and also at a novel site in the copper binding region (G1521A in the current case (converting a highly conserved cysteine to serine (C133S)); mother heterozygous for G1521A; and father heterozygous for G1541A). This case provides strong support that SCO2 mutations can result in neonatal hypotonia with an SMA 1 phenotype. SCO2 mutations should be screened in suspected SMA cases with normal smn mutation analysis and any one of; cardiomyopathy, lactic acidosis, or COX deficiency in muscle. © 2003 Wiley‐Liss, Inc.