title: Novel KIF7 missense substitutions in two patients presenting with multiple malformations and features of acrocallosal syndrome.
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.
authors.affiliation: Division of Genetics, Department of Pediatrics, University of California, San Francisco, California.
authors.forename: Sanjin
authors.initials: S
authors.lastname: Tunovic
authors.affiliation: Department of Pediatric Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Kristin W
authors.initials: KW
authors.lastname: Barañano
authors.affiliation: Department of Radiology and Biomolecular Imaging, University of California, San Francisco, California.
authors.forename: James A
authors.initials: JA
authors.lastname: Barkovich
authors.affiliation: Department of Pediatric Neurology, University of California, San Francisco, California.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Strober
authors.affiliation: Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Leila
authors.initials: L
authors.lastname: Jamal
authors.affiliation: Division of Genetics, Department of Pediatrics, University of California, San Francisco, California.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Slavotinek
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D055673:Acrocallosal Syndrome / Q000150:complications* / Q000235:genetics*; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics*; D002648:Child; D017124:Conserved Sequence; D019066:Facies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016547:Kinesins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy
chemical_list: C502069:KIF7 protein, human; D016547:Kinesins
keywords: Joubert syndrome; acrocallosal syndrome; hydrolethalus; kinesin family member