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

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Gillian Rea1,2,3, Tessa Homfray4, Jan Till4

  • 1NIHR Cardiovascular Biomedical Research Unit at Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London SW3 6NP, United Kingdom.

Cold Spring Harbor Molecular Case Studies
|January 5, 2017
PubMed

Insights

Genetic variants in NDUFB11 cause both histiocytoid cardiomyopathy and microphthalmia with linear skin defects syndrome. These findings suggest these conditions are allelic, highlighting NDUFB11

Area of Science:

  • Genetics
  • Mitochondrial Biology
  • Cardiology

Background:

  • NDUFB11 is a structural component of mitochondrial respiratory chain complex I.
  • Previously, variants in NDUFB11 were independently linked to histiocytoid cardiomyopathy (CM) and microphthalmia with linear skin defects (MLS) syndrome.
  • Other genes, including HCCS and COX7B, have also been implicated in MLS syndrome.

Purpose of the Study:

  • To report an additional case of histiocytoid CM with a de novo NDUFB11 variant.
  • To compare the phenotype of this case with previously reported MLS syndrome cases.
  • To investigate the genetic basis of histiocytoid CM and MLS syndrome and their relationship.

Main Methods:

  • Whole-exome sequencing (WES) of a family trio.
  • Clinical comparison of patients with histiocytoid CM and MLS syndrome.
  • Systematic review of WES data from published histiocytoid CM cases and analysis of four new cases.

Main Results:

  • A de novo nonsense variant in NDUFB11 (c.262C > T; p.[Arg88*]) was identified in a patient with histiocytoid CM.
  • This variant was previously reported in MLS syndrome, and the current case showed significant phenotypic overlap despite lacking typical MLS features.
  • No variants in HCCS or COX7B were found in reviewed histiocytoid CM cases.

Conclusions:

  • NDUFB11 variants are implicated in the pathogenesis of both histiocytoid CM and MLS syndrome.
  • Histiocytoid CM and MLS syndrome are allelic disorders, caused by genetic variations in the same gene.
  • NDUFB11 plays a crucial role in the development of these distinct but related conditions.

Keywords:
Wolff–Parkinson–White syndromeasymmetric, linear skin defectsdilated cardiomyopathyleft ventricular noncompaction cardiomyopathylinear hyperpigmentationmicrophthalmosoncocytic cardiomyopathyventricular fibrillation

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