Novel KIF7 mutations extend the phenotypic spectrum of acrocallosal syndrome
Publication Type:Journal Article
Source:Journal of Medical Genetics, Volume 49, Number 11, p.713-720 (2012)
Keywords:acrocallosal syndrome, Agenesis of Corpus Callosum, article, brain malformation, child, clinical article, computer assisted tomography, corpus callosum agenesis, cryptorchism, Erinaceidae, exon, face dysmorphia, female, fetus, gene amplification, gene insertion, gene locus, gene mutation, gene sequence, human, Humans, hypertelorism, hypotrophy, Intellectual Disability, Kif7 protein, Kinesin, kyphoscoliosis, macrocephaly, male, middle aged, muscle hypotonia, Mutation, newborn, phenotype, polydactyly, Preschool, preschool child, priority journal, short nose, single nucleotide polymorphism, sonic hedgehog protein, strabismus, unclassified drug
Background: Acrocallosal syndrome (ACLS) is a rare recessive disorder characterised by corpus callosum agenesis or hypoplasia, craniofacial dysmorphism, duplication of the hallux, postaxial polydactyly, and severe mental retardation. Recently, we identified mutations in KIF7, a key component of the Sonic hedgehog pathway, as being responsible for this syndrome. Methods: We sequenced KIF7 in five suspected ACLS cases, one fetus and four patients, based on facial dysmorphism and brain anomalies. Results: Seven mutations were identified at the KIF7 locus in these five cases, six of which are novel. We describe the first four compound heterozygous cases. In all patients, the diagnosis was suspected based on the craniofacial features, despite the absence of corpus callosum anomaly in one and of polydactyly in another. Hallux duplication was absent in 4/5 cases. Conclusions: These results show that ACLS has a variable expressivity and can be diagnosed even in the absence of the two major features, namely polydactyly or agenesis or hypoplasia of the corpus callosum. Facial dysmorphism with hypertelorism and prominent forehead in all the cases, as well as vermis dysgenesis with brainstem anomalies (molar tooth sign), strongly indicated the diagnosis. KIF7 should be tested in less typical patients in whom craniofacial features are suggestive of ACLS.
cited By (since 1996)3
Cite this Research Publication
Related Research Publications
- Phenotype and natural history in Marshall-Smith syndrome
- New insights into genotype-phenotype correlation for GLI3 mutations
- Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation.
- Mutations in phospholipase DDHD2 cause autosomal recessive hereditary spastic paraplegia (SPG54)
- Musculocontractural Ehlers-Danlos Syndrome (former EDS type VIB) and adducted thumb clubfoot syndrome (ATCS) represent a single clinical entity caused by mutations in the dermatan-4-sulfotransferase 1 encoding CHST14 gene