Progressive encephalopathy and complex I deficiency associated with mutations in MTND1.

• Complex I of the oxidative phosphorylation system is composed of at least 45 subunits, seven of which are encoded by mitochondrial DNA (mtDNA). In this study we have investigated two children with complex I deficiency in muscle mitochondria. Patient 1 had cerebellar ataxia from early infancy and an abnormal MRI of the brain compatible with Leigh syndrome (LS). The course was rapidly progressive with frequent exacerbations and death at 2 years and 10 months of age. Patient 2 had a lactic acidosis in the newborn period and had a severe psychomotor developmental retardation. In her teens she developed hypertrophic cardiomyopathy and died at 26 years of age because of cardiac insufficiency. Sequencing analysis of mitochondrial encoded ND genes (MTND) showed two DE NOVO mutations in MTND1 in both patients. Patient 1 had a novel heteroplasmic G3890A mutation, R195Q. Patient 2 had a heteroplasmic G3481A mutation, E59K. The G3890A mutation in patient 1 is the first identified mutation in MTND1 in association with LS and complex I deficiency. The findings in this patient as well as in patient 2 demonstrate new clinical expressions of mutations in MTND1. The findings in patient 2 also illustrates that MTND mutations may be pathogenic even at a low percentage.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Acidosis

Lactic

etiology

pathology

Adult

Base Sequence

Child

Child

Preschool

DNA Mutational Analysis

methods

DNA

Mitochondrial

chemistry

genetics

Developmental Disabilities

etiology

pathology

Electron Transport Complex I

deficiency

genetics

metabolism

Fatal Outcome

Female

Humans

Infant

Infant

Newborn

Mitochondrial Encephalomyopathies

complications

enzymology

genetics

Mutation

Missense

NADH Dehydrogenase

genetics

Oxidative Phosphorylation

Psychomotor Disorders

etiology

pathology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)