Unraveling the genetic complexity of ciliopathies in the Hutterite population

Abstract

Ciliopathies are a group of genetically heterogeneous disorders with overlapping clinical manifestations and causative genes localizing to the nonmotile cilium. Many ciliopathies are present in the genetically isolated Hutterite population. This work was initiated to identify the remaining unknown ciliopathy mutations within the population, and four additional ciliopathy mutations were found. Some Hutterite nephronophthisis patients were compound heterozygous for a c.1918delA variant in NP HP 1 and the common NP HP 1 deletion, and one patient without NP HP 1 mutations was homozygous for a c.3936_3937insAC variant in KIAAJ009. Cranioectodermal dysplasia patients in the Hutterites were homozygous for a c.17T>A variant in DPHJ, and Joubert syndrome related disorder patients without homozygous TMEM237 mutations were homozygous for a c.363 _364delT A variant in CSP P 1. Identifying the causative mutations for ciliopathies in the Hutterites allows for diagnostic testing within the population and furthers our understanding of the complexity of ciliopathies in both the Hutterites and the general population