TY - JOUR
T1 - Novel KIF7 missense substitutions in two patients presenting with multiple malformations and features of acrocallosal syndrome
AU - Tunovic, Sanjin
AU - Barañano, Kristin W.
AU - Barkovich, James A.
AU - Strober, Jonathan B.
AU - Jamal, Leila
AU - Slavotinek, Anne M.
N1 - Publisher Copyright:
© 2015 Wiley Periodicals, Inc.
PY - 2015/11
Y1 - 2015/11
N2 - 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.
AB - 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.
KW - Acrocallosal syndrome
KW - Hydrolethalus
KW - Joubert syndrome
KW - Kinesin family member
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U2 - 10.1002/ajmg.a.37249
DO - 10.1002/ajmg.a.37249
M3 - Article
C2 - 26174511
AN - SCOPUS:84946429833
SN - 1552-4825
VL - 167
SP - 2767
EP - 2776
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 11
ER -