KIF16B is a candidate gene for a novel autosomal‐recessive intellectual disability syndrome

Abstract

Intellectual disability (ID) and global developmental delay are closely related; the latter is reserved for children under the age of 5 years as it is challenging to reliably assess clinical severity in this population. ID is a common condition, with up to 1%-3% of the population being affected and leading to a huge social and economic impact. ID is attributed to genetic abnormalities most of the time; however, the exact role of genetic involvement in ID is yet to be determined. Whole exome sequencing (WES) has gained popularity in the workup for ID, and multiple studies have been published examining the diagnostic yield in identification of the disease-causing variant (16%-55%), with the genetic involvement increasing as intelligence quotient decreases. WES has also accelerated novel disease gene discovery in this field. We identified a novel biallelic variant in the KIF16B gene (NM_024704.4:c.3611T > G) in two brothers that may be the cause of their phenotype.

‘Kinesinopathies’: emerging role of the kinesin family member genes in birth defects

“…48 In particular, KIF7 gene variants have been related to various anomalies of the hands (tapered fingers, fifth finger clinodactyly, brachydactyly, preaxial or postaxial polydactyly, bifid terminal phalanges of the thumbs, spindle-shaped fingers, clinodactyly and soft tissue webbing) and feet (toe syndactyly, preaxial or postaxial polydactyly, and duplicated halluces). 22 CAKUT and genital anomalies are reported in various kinesinopathies including renal agenesis or hypoplasia (KIF14 37 and KIF12 52 ), ureteral hypoplasia (KIF14 37 ), congenital megabladder (KIF12 52 ) and vesicoureteral reflux (KIF12 52 ), uterine hypoplasia and vaginal atresia (KIF14 37 ) and hypospadias and chordae (KIF16B 49 ).…”

Connecting phenotype to genotype: PheWAS-inspired analysis of autism spectrum disorder

“…Copy number variants of LINGO2 have been found in ASD cases (Williams et al, 2019 ), and LINGO2 deletions have been reported in individuals with developmental delay, autistic behavior, and craniofacial abnormalities (Jansen et al, 2019 ). Bi-allelic variants in the KIF16B gene may be linked to autosomal recessive intellectual disability syndrome (Alsahli et al, 2018 ). We observe from the clustering results of G D ( Table 3 ), that its cluster C5 does not align with any of the clusters from the fused or indirect graphs.…”

Insulin signaling accelerates the anterograde movement of Rab4 vesicles in axons through Klp98A/KIF16B recruitment via Vps34-PI3Kinase

“…In addition, we also noted that not all motile Klp98A-positive vesicles in axons have Rab4, indicating that Klp98A transports other cargos apart from Rab4 vesicles in axons. Interestingly, mutations in the cargo-binding PX domain of KIF16B have recently been reported in patients with intellectual disability syndrome ( Alsahli et al, 2018 ), although the underlying cause remains to be investigated. Thus, our results could provide a critical mechanistic input because perturbations in Rab4 levels and functionality also affect synaptic homeostasis, which happens to be one of the hallmarks of intellectual disabilities ( Zoghbi & Bear, 2012 ).…”