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Short report
A human laterality disorder associated with recessive CCDC11 mutation
  1. Zeev Perles1,
  2. Yuval Cinnamon2,
  3. Asaf Ta-Shma3,
  4. Avraham Shaag2,
  5. Tom Einbinder3,
  6. Azaria J J T Rein1,
  7. Orly Elpeleg2
  1. 1Department of Pediatric Cardiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  2. 2Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  3. 3Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
  1. Correspondence to Professor Orly Elpeleg, Hadassah-Hebrew University Medical Centre, Jerusalem 91120, Israel; elpeleg{at}hadassah.org.il

Abstract

Background Significant advancements in understanding the molecular pathophysiology of laterality determination were recently made. However, there are large gaps in our knowledge of the initial processes that lead to laterality defects, such as heterotaxy syndrome (HS, also known as situs ambiguous) and situs inversus totalis (SIT). The former refers to abnormal distribution of visceral organs, and the latter refers to a complete laterality inversion of both abdominal and thoracic viscera.

Methods In order to identify a mutated gene in SIT and HS patients, the authors performed homozygosity mapping in a consanguineous family with laterality disorders identified in two siblings.

Results A homozygous deleterious mutation in the CCDC11 gene was identified in the patients. The mutation resulted in an abnormally smaller protein in the patient's skin fibroblasts. The parents and five healthy siblings were heterozygous for the mutation, which was not present in 112 anonymous controls.

Conclusions Few genes have been associated with both SIT and HS, usually accompanied by other abnormalities. The authors suggest that CCDC11 is associated with autosomal recessive laterality defects of diverse phenotype resulting in SIT in one individual family member who is otherwise healthy, and in complex laterality anomalies (HS) in another member. This report underscores the importance of CCDC11 in laterality determination.

  • Cilia
  • situs inversus totalis
  • heterotaxy
  • CCDC11
  • homozygousity mapping
  • developmental
  • congenital heart disease
  • cardiovascular medicine
  • cardiomyopathy
  • genetics
  • neuromuscular disease
  • molecular genetics

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Footnotes

  • ZP and YC contributed equally to this work.

  • Competing interests None.

  • Patient consent The parents signed the Hadassah consent form, translated to Arabic.

  • Ethics approval Ethics approval was provided by the Hadassah Helsinki committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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