title: Dyggve-Melchior-Clausen syndrome: novel splice mutation with atlanto-axial subluxation.
abstract: Dyggve-Melchior-Clausen (DMC) syndrome is a rare autosomal recessive disorder characterized by the association of a progressive spondyloepimetaphyseal dysplasia and mental retardation ranging from mild to severe. The disorder results from mutations in the dymeclin (DYM) gene in the 18q12-12.1 chromosomal region. We report two siblings with classical clinical and radiological features of DMC and asymptomatic atlanto-axial dislocation. A novel homozygous splice-site mutation (IVS15+3G>T) was detected. Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed that this mutation affects normal splicing. To the best of our knowledge, this is the first report of DMC from Saudi Arabia. The splice mutation noted in our patients was compared to the previously reported cases and supports the hypothesis that loss of DYM function is the likely mechanism of disease pathogenesis. In conclusion, distinction between this type of skeletal dysplasia and Morquio disease (MPS IV) is important for paediatricians and clinical geneticist in providing standard patient care and genetic counselling.
authors.affiliation: Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, MBC 75, PO Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Ola
authors.initials: O
authors.lastname: Khalifa
authors.forename: Faiqa
authors.initials: F
authors.lastname: Imtiaz
authors.forename: Nadia
authors.initials: N
authors.lastname: Al-Sakati
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Manea
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Owain
mesh_terms: D000293:Adolescent; D001268:Atlanto-Axial Joint / Q000002:abnormalities*; D002887:Chromosomes, Human, Pair 18; D004392:Dwarfism / Q000175:diagnosis / Q000235:genetics; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000151:congenital / Q000175:diagnosis / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D022821:RNA Splice Sites; D012529:Saudi Arabia; D035781:Siblings
chemical_list: C477370:DYM protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D022821:RNA Splice Sites