Histiocytoid cardiomyopathy and microphthalmia with linear skin defects syndrome: phenotypes linked by truncating variants in NDUFB11

• DOI: 10.1101/mcs.a001271
• Publication Date: 2017-01-03T14:40:26Z
• Authors: Gillian Rea; Tessa Homfray; Jan Till; Ferran Roses-Noguer; Rachel J. Buchan; Sam Wilkinson; Alicja Wilk; Roddy Walsh; Shibu John; Shane McKee; Fiona J. Stewart; Victoria Murday; Robert W. Taylor; Michael Ashworth; A. John Baksi; Piers Daubeney; Sanjay Prasad; Paul J.R. Barton; Stuart A. Cook; James S. Ware
• Keywords: Microphthalmia-associated transcription factor; Exome

Variants in NDUFB11, which encodes a structural component of complex I the mitochondrial respiratory chain (MRC), were recently independently reported to cause histiocytoid cardiomyopathy (histiocytoid CM) and microphthalmia with linear skin defects syndrome (MLS syndrome). Here we report an additional case CM, carries de novo nonsense variant NDUFB11 (ENST00000276062.8: c.262C > T; p.[Arg88*]) identified using whole-exome sequencing (WES) family trio. An identical has been previously association MLS syndrome. The describe here lacked diagnostic features syndrome, but detailed clinical comparison two cases revealed significant phenotypic overlap. Heterozygous variants HCCS (which important mitochondrially targeted protein) COX7B, which, like protein MRC, have also including both CM. However, systematic review WES data from published CM cases, alongside four presented for first time, did not identify any these genes. We conclude that play role pathogenesis disorders are allelic (genetically related).