Hoff et al. (2013) reported 8 patients from 6 unrelated families with nephronophthisis. Affected individuals in 5 families had infantile onset of progressive pol...
Hoff et al. (2013) reported 8 patients from 6 unrelated families with nephronophthisis. Affected individuals in 5 families had infantile onset of progressive polycystic kidney disease leading to renal failure, whereas those in 1 family showed juvenile onset of the disorder. Some patients had nonenlarged cystic kidneys and no extrarenal manifestations, whereas others had enlarged renal size and severe extrarenal defects, including hypertrophic obstructive cardiomyopathy, aortic stenosis, pulmonary stenosis, patent ductus arteriosus, situs inversus, and periportal liver fibrosis.
The transmission pattern of NPHP16 in the families reported by Hoff et al. (2013) was consistent with autosomal recessive inheritance.
By linkage analysis of a consanguineous Turkish family with NPHP, Hoff et al. (2013) found linkage to an 8-Mb region spanning the ANKS6 gene on chromosome 9 (maximum lod score of 2.41).
▼ Molecular Genetics
In affected members of 6 unrelated families with nephronophthisis-16, Hoff et al. (2013) identified 6 different homozygous mutations in the ANKS6 gene (see, e.g., 615370.0001-615370.0005). There were 2 truncating mutations, 2 splice site mutations, and 2 missense mutations. The gene was chosen for study based on findings in animal models and on the interactive role of ANKS6 with other cilia-related proteins. Patients with missense mutations had no extrarenal manifestations, whereas those with splice site and truncating mutations had additional features. The findings indicated that the ANKS6 gene has a role in renal and cardiovascular development.