BACKGROUND: Mutations in the nuclear-encoded subunits of complex I of the mitochondrial respiratory chain are a recognized cause of Leigh syndrome (LS). Recently, 6 mutations in the NDUFS1 gene were identified in 3 families. OBJECTIVE: To describe a Spanish family with LS, complex I deficiency in muscle, and a novel mutation in the NDUFS1 gene. DESIGN: Using molecular genetic approaches, we identified the underlying molecular defect in a patient with LS with a complex I defect. PATIENT: The proband was a child who displayed the clinical features of LS. RESULTS: Muscle biochemistry results showed a complex I defect of the mitochondrial respiratory chain. Sequencing analysis of the mitochondrial DNA-encoded ND genes, the nuclear DNA-encoded NDUFV1, NDUFS1, NDUFS2, NDUFS4, NDUFS6, NDUFS7, NDUFS8, and NDUFAB1 genes, and the complex I assembly factor CIA30 gene revealed a novel homozygous L231V mutation (c.691C-->G) in the NDUFS1 gene. The parents were heterozygous carriers of the L231V mutation. CONCLUSIONS: Identifying nuclear mutations as a cause of respiratory chain disorders will enhance the possibility of prenatal diagnosis and help us understand how molecular defects can lead to complex I deficiency.
BACKGROUND: Mutations in the nuclear-encoded subunits of complex I of the mitochondrial respiratory chain are a recognized cause of Leigh syndrome (LS). Recently, 6 mutations in the NDUFS1 gene were identified in 3 families. OBJECTIVE: To describe a Spanish family with LS, complex I deficiency in muscle, and a novel mutation in the NDUFS1 gene. DESIGN: Using molecular genetic approaches, we identified the underlying molecular defect in a patient with LS with a complex I defect. PATIENT: The proband was a child who displayed the clinical features of LS. RESULTS: Muscle biochemistry results showed a complex I defect of the mitochondrial respiratory chain. Sequencing analysis of the mitochondrial DNA-encoded ND genes, the nuclear DNA-encoded NDUFV1, NDUFS1, NDUFS2, NDUFS4, NDUFS6, NDUFS7, NDUFS8, and NDUFAB1 genes, and the complex I assembly factor CIA30 gene revealed a novel homozygous L231V mutation (c.691C-->G) in the NDUFS1 gene. The parents were heterozygous carriers of the L231V mutation. CONCLUSIONS: Identifying nuclear mutations as a cause of respiratory chain disorders will enhance the possibility of prenatal diagnosis and help us understand how molecular defects can lead to complex I deficiency.
Authors: Rolf J R J Janssen; Leo G Nijtmans; Lambert P van den Heuvel; Jan A M Smeitink Journal: J Inherit Metab Dis Date: 2006-07-11 Impact factor: 4.982
Authors: S Dato; M Soerensen; V Lagani; A Montesanto; G Passarino; K Christensen; Q Tan; L Christiansen Journal: Exp Gerontol Date: 2014-01-22 Impact factor: 4.032
Authors: Helen A L Tuppen; Vanessa E Hogan; Langping He; Emma L Blakely; Lisa Worgan; Mazhor Al-Dosary; Gabriele Saretzki; Charlotte L Alston; Andrew A Morris; Michael Clarke; Simon Jones; Anita M Devlin; Sahar Mansour; Zofia M A Chrzanowska-Lightowlers; David R Thorburn; Robert McFarland; Robert W Taylor Journal: Brain Date: 2010-09-06 Impact factor: 13.501