A human laterality disorder associated with recessive CCDC11 mutation.

Area of Science:

• Genetics
• Developmental Biology
• Molecular Medicine

Background:

• Laterality determination is complex, with significant knowledge gaps regarding initial molecular processes.
• Laterality defects like heterotaxy syndrome (HS) and situs inversus totalis (SIT) involve abnormal visceral organ positioning.

Purpose of the Study:

• To identify the genetic cause of laterality disorders in a consanguineous family.
• To investigate the role of CCDC11 in the pathogenesis of HS and SIT.

Main Methods:

• Homozygosity mapping was employed in a consanguineous family with affected siblings.
• Genetic analysis was performed to identify mutations in candidate genes.

Main Results:

• A homozygous deleterious mutation in the CCDC11 gene was identified in affected individuals.
• The mutation led to a truncated CCDC11 protein in patient fibroblasts.
• The mutation was absent in healthy family members and controls.

Conclusions:

• CCDC11 mutations are associated with autosomal recessive laterality defects, presenting diverse phenotypes including SIT and HS.
• This finding highlights CCDC11's critical role in human laterality determination.
• CCDC11 is implicated in both isolated and complex laterality disorders.