Mitochondrial Complex I Deficiency, Nuclear Type 25

A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 25 (MC1DN25) is caused by homozygous or compound heterozygous mutation in the NDUFB3 gene (603839) on chromosome 2q33.

For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010.

Clinical Features

Calvo et al. (2012) reported a female infant, born of unrelated parents of British and Dutch descent, with severe lethal mitochondrial complex I deficiency. The pregnancy was complicated by intrauterine growth retardation and premature birth at 31 weeks' gestation; respiratory insufficiency required extensive artificial ventilation in the neonatal period. After discharge home, she showed hypotonia with poor feeding and significant lactic acidosis and died unexpectedly at age 4 months. Skeletal muscle biopsy showed variation in the shape and size of muscle fibers, and atrophic fibers containing nemaline rods. Biochemical analysis showed complex I deficiency with borderline low complex III deficiency, the latter of which may have been an artifact.

Haack et al. (2012) reported a patient with complex I deficiency who had encephalopathy, myopathy, hypotonia, developmental delay, and lactic acidosis.

Molecular Genetics

In a female infant, born of unrelated parents of British and Dutch descent, with severe lethal mitochondrial complex I deficiency, Calvo et al. (2012) identified a homozygous missense mutation in the NDUFB3 gene (W22R; 603839.0001). The unaffected mother was a carrier; DNA from the father was not available.

In a patient with complex I deficiency, Haack et al. (2012) identified compound heterozygosity for 2 mutations in the NDUFB3 gene: the previously described W22R mutation and G70X (603839.0002). The mutations were identified by exome sequencing.