Genes, Vol. 15, Pages 500: Biallelic NDUFA4 Deletion Causes Mitochondrial Complex IV Deficiency in a Patient with Leigh Syndrome
Genes, Vol. 15, Pages 500: Biallelic NDUFA4 Deletion Causes Mitochondrial Complex IV Deficiency in a Patient with Leigh Syndrome
Genes doi: 10.3390/genes15040500
Authors:
Doriana Misceo
Petter Strømme
Fatemeh Bitarafan
Maninder Singh Chawla
Ying Sheng
Sandra Monica Bach de Courtade
Lars Eide
Eirik Frengen
Oxidative phosphorylation involves a complex multi-enzymatic mitochondrial machinery critical for proper functioning of the cell, and defects herein cause a wide range of diseases called “primary mitochondrial disorders” (PMDs). Mutations in about 400 nuclear and 37 mitochondrial genes have been documented to cause PMDs, which have an estimated birth prevalence of 1:5000. Here, we describe a 4-year-old female presenting from early childhood with psychomotor delay and white matter signal changes affecting several brain regions, including the brainstem, in addition to lactic and phytanic acidosis, compatible with Leigh syndrome, a genetically heterogeneous subgroup of PMDs. Whole genome sequencing of the family trio identified a homozygous 12.9 Kb deletion, entirely overlapping the NDUFA4 gene. Sanger sequencing of the breakpoints revealed that the genomic rearrangement was likely triggered by Alu elements flanking the gene. NDUFA4 encodes for a subunit of the respiratory chain Complex IV, whose activity was significantly reduced in the patient’s fibroblasts. In one family, dysfunction of NDUFA4 was previously do...
Source: Genes - Category: Genetics & Stem Cells Authors: Doriana Misceo Petter Str ømme Fatemeh Bitarafan Maninder Singh Chawla Ying Sheng Sandra Monica Bach de Courtade Lars Eide Eirik Frengen Tags: Article Source Type: research
More News: Brain | Genetics | Leigh Syndrome | Mitochondrial Disease | Neurology | Respiratory Medicine