Mitochondrial Complex Iii Deficiency, Nuclear Type 4

A number sign (#) is used with this entry because of evidence that mitochondrial complex III deficiency nuclear type 4 (MC3DN4) is caused by homozygous mutation in the UQCRQ gene (612080) on chromosome 5q31.

For a general phenotypic description and a discussion of genetic heterogeneity of mitochondrial complex III deficiency, see MC3DN1 (124000).

Clinical Features

Barel et al. (2008) reported a large consanguineous Israeli Bedouin kindred in which 25 individuals had an autosomal recessive syndrome comprising severe psychomotor retardation and extrapyramidal signs. Affected individuals seemed normal at birth without any dysmorphic features, but showed developmental delay in the first few months of life. Neurologic features included dystonia, athetoid movements, ataxia, mild axial hypotonia, increased tone, hyperreflexia, and inability to walk unsupported. Other features included restlessness, marked global dementia, severe defects in verbal receptive communication, and near total absence of expressive communication skills, with inability to express any words at any age. The phenotype was not lethal, with some affected individuals surviving well into their thirties. Brain MRI in 5 patients showed bilateral symmetric abnormal findings in the basal ganglia. Serum lactate was mildly elevated and muscle biopsies showed a reduction in mitochondrial complex III activity.

Inheritance

The transmission pattern of mitochondrial complex III deficiency in the family reported by Barel et al. (2008) was consistent with autosomal recessive inheritance.

Mapping

By genomewide linkage analysis of a consanguineous family with mitochondrial complex III deficiency, Barel et al. (2008) found a homozygosity locus of approximately 9 cM on chromosome 5q31 that was further narrowed down to 2.14 cM (lod score of 8.82).

Molecular Genetics

In affected members of a large Israeli Bedouin kindred with complex III deficiency, Barel et al. (2008) identified a homozygous mutation in the UQCRQ gene (612080.0001).