title: A mutation in KIF7 is responsible for the autosomal recessive syndrome of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance.
abstract: BACKGROUND
  We previously reported the existence of a unique autosomal recessive syndrome consisting of macrocephaly, multiple epiphyseal dysplasia and distinctive facial appearance mapping to chromosome 15q26.
  
  
  METHODS
  In this manuscript, we have used whole exome sequencing on two affected members of a consanguineous family with this condition and carried out detailed bioinformatics analysis to elucidate the causative mutation.
  
  
  RESULTS
  Our analysis resulted in the identification of a homozygous p.N1060S missense mutation in a highly conserved residue in KIF7, a regulator of Hedgehog signaling that has been recently found to be causing Joubert syndrome, fetal hydrolethalus and acrocallosal syndromes. The phenotype in our patients partially overlaps with the phenotypes associated with those syndromes but they also exhibit some distinctive features including multiple epiphyseal dysplasia.
  
  
  CONCLUSIONS
  We report the first missense homozygous disease-causing mutation in KIF7 and expand the clinical spectrum associated with mutations in this gene to include multiple epiphyseal dysplasia. The missense nature of the mutation might account for the unique presentation in our patients.
authors.affiliation: Department of Pathology, Faculty of Medicine and Health Sciences, United Arab Emirates University, P,O, Box 17666, Al-Ain, United Arab Emirates.
authors.forename: Bassam R
authors.initials: BR
authors.lastname: Ali
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Silhavy
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Akawi
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Gleeson
authors.forename: Lihadh
authors.initials: L
authors.lastname: Al-Gazali
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D003241:Consanguinity; D019066:Facies; D005808:Genes, Recessive; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D058627:Megalencephaly / Q000235:genetics*; D020125:Mutation, Missense; D010009:Osteochondrodysplasias / Q000235:genetics*; D010641:Phenotype
chemical_list: C502069:KIF7 protein, human; D016547:Kinesins