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Ciliary Genes TBC 1 D 32 / C6orf170 and SCLT 1 are Mutated in Patients with OFD Type IX
Author(s) -
Adly Nouran,
Alhashem Amal,
Ammari Amer,
Alkuraya Fowzan S.
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22477
Subject(s) - ciliopathy , ciliopathies , biology , ciliogenesis , cilium , genetics , joubert syndrome , phenotype , polydactyly , exome sequencing , genetic heterogeneity , gene
ABSTRACT Clinical syndromes caused by defects in the primary cilium are heterogeneous but there are recurrent phenotypic manifestations that define them as a collective group known as ciliopathies. Dozens of genes have been linked to various ciliopathies but large patient cohorts have clearly revealed the existence of additional genetic heterogeneity, which is yet to be fully appreciated. In our search for novel ciliopathy‐linked genes through the study of unmapped ciliopathy phenotypes, we have identified two simplex cases with a severe ciliopathy phenotype consistent with oro‐facio‐digital syndrome type IX featuring midline cleft, microcephaly, and colobomatous microphathalmia/anophthalmia. In addition, there was variable presence of polydactyly, absent pituitary, and congenital heart disease. The autozygome of each index harbored a single novel truncating variant as revealed by exome sequencing, and the affected genes ( SCLT 1 and TBC 1 D 32/C6orf170 ) have established roles in centrosomal biology and ciliogenesis. Our findings suggest a previously unrecognized role of SCLT 1 and TBC1D 32 in the pathogenesis of ciliopathy in humans.