Novel KIF7 missense substitutions in two patients presenting with multiple malformations and features of acrocallosal syndrome

Sanjin Tunovic, Kristin Baranano, James A. Barkovich, Jonathan B. Strober, Leila Jamal, Anne M. Slavotinek

Research output: Contribution to journalArticle

Abstract

We present two children who both had two missense mutations in the Kinesin Family Member 7 (KIF7) gene. A seven year old female with severe developmental delays, failure to thrive and growth retardation, infantile spasms, a cardiac vascular ring and right-sided aortic arch, imperforate anus, hydronephrosis with a right renal cyst, syndactyly and abnormal white matter was a compound heterozygote for c.3365C>G, predicting p.(Ser1122Trp) that was maternally inherited and c.2482G>A, predicting p.(Val828Met) that was paternally inherited. An eight year old female with severe developmental delays, epilepsy, left postaxial polydactyly of the hand and abnormalities of brain development including hydrocephalus, pachygyria and absence of the body and splenium of the corpus callous was a compound heterozygote for c.461G>A, predicting p.(Arg154Gln) and c.2959 G>A, predicting p.(Glu987Lys) that was maternally inherited and her father was unavailable for testing. The presentations in these children include features of acrocallosal syndrome, such as hypoplasia of the corpus callosum, enlarged ventricles, facial dysmorphism with a prominent forehead and broad halluces in the first child, but included atypical findings for individuals previously reported to have truncating mutations in KIF7, including imperforate anus, infantile spasms and severe growth retardation. We conclude that these phenotypes may result from the KIF7 sequence variants and abnormal hedgehog signaling, but that the full spectrum of KIF7-associated features remains to be determined.

Original languageEnglish (US)
Pages (from-to)2767-2776
Number of pages10
JournalAmerican Journal of Medical Genetics, Part A
Volume167
Issue number11
DOIs
StatePublished - Nov 1 2015

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Acrocallosal Syndrome
Kinesin
Imperforate Anus
Infantile Spasms
Heterozygote
Lissencephaly
Hallux
Syndactyly
Failure to Thrive
Forehead
Hydronephrosis
Corpus Callosum
Missense Mutation
Hydrocephalus
Growth
Thoracic Aorta
Fathers
Blood Vessels
Cysts
Epilepsy

Keywords

  • Acrocallosal syndrome
  • Hydrolethalus
  • Joubert syndrome
  • Kinesin family member

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Novel KIF7 missense substitutions in two patients presenting with multiple malformations and features of acrocallosal syndrome. / Tunovic, Sanjin; Baranano, Kristin; Barkovich, James A.; Strober, Jonathan B.; Jamal, Leila; Slavotinek, Anne M.

In: American Journal of Medical Genetics, Part A, Vol. 167, No. 11, 01.11.2015, p. 2767-2776.

Research output: Contribution to journalArticle

Tunovic, Sanjin ; Baranano, Kristin ; Barkovich, James A. ; Strober, Jonathan B. ; Jamal, Leila ; Slavotinek, Anne M. / Novel KIF7 missense substitutions in two patients presenting with multiple malformations and features of acrocallosal syndrome. In: American Journal of Medical Genetics, Part A. 2015 ; Vol. 167, No. 11. pp. 2767-2776.
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