De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy

Monica H. Wojcik, Kyoko Okada, Sanjay P. Prabhu, Dan W. Nowakowski, Keri Ramsey, Chris Balak, Sampath Rangasamy, Catherine A. Brownstein, Klaus Schmitz-Abe, Julie S. Cohen, Ali Fatemi, Jiahai Shi, Ellen P. Grant, Vinodh Narayanan, Hsin-Yi Henry Ho, Pankaj B. Agrawal

Research output: Contribution to journalArticle

2 Scopus citations


KIF26B is a member of the kinesin superfamily with evolutionarily conserved functions in controlling aspects of embryogenesis, including the development of the nervous system, though its function is incompletely understood. We describe an infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. We performed whole exome sequencing on the trio and identified a de novo KIF26B missense variant, p.Gly546Ser, in the proband. This variant alters a highly conserved amino acid residue that is part of the phosphate-binding loop motif and motor-like domain and is deemed pathogenic by several in silico methods. Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity. Overall, KIF26B may play a critical role in the brain development and, when mutated, cause pontocerebellar hypoplasia with arthrogryposis.

Original languageEnglish (US)
JournalAmerican Journal of Medical Genetics, Part A
StateAccepted/In press - Jan 1 2018



  • arthrogryposis
  • KIF26B
  • kinesin
  • microcephaly
  • pontocerebellar hypoplasia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Wojcik, M. H., Okada, K., Prabhu, S. P., Nowakowski, D. W., Ramsey, K., Balak, C., Rangasamy, S., Brownstein, C. A., Schmitz-Abe, K., Cohen, J. S., Fatemi, A., Shi, J., Grant, E. P., Narayanan, V., Ho, H-Y. H., & Agrawal, P. B. (Accepted/In press). De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy. American Journal of Medical Genetics, Part A.