|PDH Complex and Mitochondrial Respiratory Chain Complex V Deficiency Panel by Massively Parallel Sequencing (BCM-MitomeNGSSM)
||Pyruvate dehydrogenase deficiency is a well defined biochemical defect that is clinically highly heterogeneous. It is one of the major causes of severe primary lactic acidosis in the newborn period and infancy, but can also present as a more chronic neurodegenerative disease with extensive cerebral atrophy and structural anomalies in the brain, as seen in Leigh syndrome or as episodic ataxia. The clinical presentation may overlap with defects in mitochondrial complex V (ATP synthase), where patients also present with lactic acidosis yet routine ETC activities may appear normal if complex V is not measured. Some cases of complex V deficiency may exhibit neonatal-onset hypotonia, hyperammonemia, hypertrophic cardiomyopathy, and 3-methylglutaconic aciduria, and can be due to either nuclear or mtDNA gene defects. The PDH/Complex V panel consisting of genes involved in both PDH and complex V deficiency is a single test for the molecular diagnosis of patients with clinical symptoms indicative of either disorder in whom enzyme testing may have been normal due to the limitations of biochemical testing.
Nine nuclear genes involved in pyruvate dehydrogenase deficiency and mitochondrial complex V deficiency are analyzed by the newly developed and clinically validated approach of Massively Parallel Sequencing (MPS) using Next Generation Sequence (NGS) technology. The genes analyzed by this panel are tabulated below . Sanger sequencing of these genes is also available using the associated individual test codes.
PDHA1 (#3165), PDHB (#3895), DLAT (#3915), DLD (#3460), PDHX (#3920), PDP1 (#3890), ATPAF2 (ATP12) (#3270), ATP5E (#3290) and TMEM70 (#3735).
All coding exons of these 9 nuclear genes and at least 20 base pairs of flanking intronic sequences are analyzed. All exonic variants and intronic variants within 20 bp of the exon/intron boundary will be reported. Sequence analysis will not detect genomic structural rearrangements (e.g. heterozygous deletions, duplications, and inversions), large heterozygous insertion mutations (e.g. ALU mediated insertion), and mutations within the promoter or deep intronic regions. Mutations and novel variants detected by NGS are confirmed by Sanger sequencing.
Mitomet deletion/duplication analysis (#2003) for the genes covered by this panel is also available.
||Targeted Capture followed by Massively Parallel Sequencing
||PDHA1, PDHB, DLAT, DLD, PDHX, PDP1, ATPAF2 (ATP12), ATP5E and TMEM70