Novel KIF7 mutations extend the phenotypic spectrum of acrocallosal syndrome
| Autor: | Valérie Cormier-Daire, Philip L. Beales, Férechté Encha-Razavi, Albert Schinzel, Anita Rauch, Nathalie Boddaert, Audrey Putoux, Caroline Alby, Julie Litzler, Sheela Nampoothiri, Deborah Bartholdi, Nadia Elkhartoufi, Rajesh Kannan, Tania Attié-Bitach, Nicole Laurent, Laurence Faivre, Sophie Thomas, Amale Ichkou, Arnold Munnich, Michel Vekemans |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Acrocallosal Syndrome Kinesins Dysgenesis Fetus Intellectual Disability Genetics medicine Humans Craniofacial Hypertelorism Genetics (clinical) Polydactyly Corpus Callosum Agenesis business.industry Anatomy Middle Aged medicine.disease Acrocallosal syndrome Hypoplasia Phenotype Agenesis Child Preschool Mutation Female medicine.symptom Agenesis of Corpus Callosum business |
| Zdroj: | Journal of medical genetics. 49(11) |
| ISSN: | 1468-6244 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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