The many faces of KIF7

Abstract

Mutations in KIF7, the gene that encodes a component of the kinesin complex of anterograde intraflagellar transport in the cilia, have been reported to cause a range of phenotypes including hydrolethalis, acrocallosal syndrome and Joubert syndrome. In a cohort of patients with various neurogenetic phenotypes, we identified novel KIF7 mutations in two families that span the known phenotypic spectrum of KIF7-related disorders. Surprisingly, we also identified a novel truncating KIF7 mutation in a third consanguineous family, in which the index presented with intellectual disability but no overt signs of ciliopathy, and his brain magnetic resonance imaging revealed an isolated dysgenesis of corpus callosum. This small cohort contributes novel pathogenic alleles of KIF7 and suggests that KIF7-related phenotypes can include isolated dysgenesis of corpus callosum with intellectual disability, thus expanding the range of phenotypes that warrant sequencing of this gene.

A homozygous deleterious CDK10 mutation in a patient with agenesis of corpus callosum, retinopathy, and deafness

“…Thus, CDK10 defect is likely associated with a new form of ciliopathy phenotype, bearing clinical similarity to CycM defect only in the facial appearance of the patients, and sharing the retinal involvement, the hearing loss and the short stature with many patients with ciliopathies including Senior–Løken syndrome, Bardet‐Biedl syndrome and Alström syndrome, and the corpus callosum agenesis with patients suffering from KIF7 and OFD1 ciliopathies (Barakeh et al, ; Del Giudice et al, ). Still, additional, unrelated patients will be needed to prove the association between this phenotype and CDK10 mutation, but until that occurs, the present report provides compelling evidence, worthy of publication.…”

Co-occurrence of mutations in KIF7 and KIAA0556 in Joubert syndrome with ocular coloboma, pituitary malformation and growth hormone deficiency: a case report and literature review

“…The co-occurrence of variants in these genes has not been reported thus far. Mutations in KIF7 have been associated with a broad spectrum of ciliopathies with variable features ranging from lethal hydrocephalus, with or without polydactyly (HLS), to craniofacial dysmorphism, ID, and brain abnormalities with or without MTS (ACLS or JBTS12) [14,17]. Of note, KIF7 encodes a member of a family of 14 kinesin motor proteins known to localize from the base to the tip of the cilium governing its structure and length, its architecture and transport [3].…”

Novel <b><i>KIF7</i></b> Mutation in a Tunisian Boy with Acrocallosal Syndrome: Case Report and Review of the Literature

“…in the present case report) to only mild dysgenesis of the corpus callosum and intellectual disability without other associated features [Barakeh et al, 2015].…”

“…Subsequently, all of these overlapping KIF7-associated syndromes (ACLS, JBTS12, HLS2, and the new phenotype associated with multiple epiphyseal dysplasia) have been suggested to constitute the phenotypic spectrum of KIF7 -related ciliopathies [Putoux et al, 2012]; an overview of the major symptoms of these syndromes is given in table 1 . So far, genotype-phenotype correlations are hard to establish; notably, one mutation has been found in homozygous state in a 14-year-old patient with ACLS, in a family with lethal HLS [Putoux et al, 2011] and in a boy only with intellectual disability [Barakeh et al, 2015].…”

“…com/product/hgmd) [Barakeh et al, 2015;Karaer et al, 2015] to date which include nonsense, missense and splice site mutations as well as small deletions and span the entire gene without a hot spot region ( fig. 4 ).…”