title: Mental retardation and abnormal skeletal development (Dyggve-Melchior-Clausen dysplasia) due to mutations in a novel, evolutionarily conserved gene.
abstract: Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC) are similar, rare autosomal recessive osteochondrodysplasias. The radiographic features and cartilage histology in DMC and SMC are identical. However, patients with DMC exhibit significant developmental delay and mental retardation, the major features that distinguish the two conditions. Linkage studies localized the SMC and DMC disease genes to chromosome 18q12-21.1, providing evidence suggesting that they are allelic disorders. Sequence analysis of the coding exons of the FLJ90130 gene, a highly evolutionarily conserved gene within the recombination interval defined in the linkage study, identified mutations in SMC and DMC patients. The affected individuals in two consanguinous DMC families were homozygous for a stop codon mutation and a frameshift mutation, respectively, demonstrating that DMC represents the FLJ90130-null phenotype. The data confirm the hypothesis that SMC and DMC are allelic disorders and identify a gene necessary for normal skeletal development and brain function.
authors.affiliation: Medical Genetics-Birth Defects Center, Ahmanson Department of Pediatrics, Cedars-Sinai Research Institute and Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90048, USA. dan.cohn@cshs.org
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Cohn
authors.forename: Nadia
authors.initials: N
authors.lastname: Ehtesham
authors.forename: Deborah
authors.initials: D
authors.lastname: Krakow
authors.forename: Sheila
authors.initials: S
authors.lastname: Unger
authors.forename: Alan
authors.initials: A
authors.lastname: Shanske
authors.forename: Kent
authors.initials: K
authors.lastname: Reinker
authors.forename: Berkley R
authors.initials: BR
authors.lastname: Powell
authors.forename: David L
authors.initials: DL
authors.lastname: Rimoin
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002887:Chromosomes, Human, Pair 18; D003241:Consanguinity; D002658:Developmental Disabilities / Q000235:genetics / Q000503:physiopathology; D019143:Evolution, Molecular; D005260:Female; D008040:Genetic Linkage; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid