Dyggve-Melchior-Clausen syndrome and Smith-McCort dysplasia: clinical and molecular findings in three families supporting genetic heterogeneity in Smith-McCort dysplasia.
Dyggve-Melchior-Clausen syndrome (DMC) (MIM 223800) and Smith-McCort dysplasia (SMC) (MIM 607326) are rare allelic autosomal recessive spondylo-epi-metaphyseal dysplasias (SEMDs) characterized by similar skeletal manifestations. Both phenotypes have been mapped to chromosome 18q21.1 and mutations in the DYM (dymeclin) gene were identified in 13 families with DMC and in two families with SMC. Most mutations identified in DMC predict a loss of function, while those identified in SMC are mainly missense mutations, presumably associated with residual DYM activity and a less severe phenotype. We studied three consanguineous families from Turkey, Lebanon, and Georgia, one with SMC and two with DMC and identified different homozygous DYM mutations (IVS3 194-1G > A, 938_942delTGTCT) in the DMC families. No mutation was identified in the SMC family, possibly suggesting genetic heterogeneity of this disorder.
Neumann
Luitgard M
LM
Institute of Human Genetics, Charité University Medicine Berlin, Berlin, Germany. luitgard.neumann@charite.de
El Ghouzzi
Vincent
V
Paupe
Vincent
V
Weber
Hans-Peter
HP
Fastnacht
Elisabeth
E
Leenen
Andreas
A
Lyding
Sigrid
S
Klusmann
Anne
A
Mayatepek
Ertan
E
Pelz
Jörg
J
Cormier-Daire
Valerie
V
D000293:Adolescent; D001483:Base Sequence; D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005347:Fibroblasts / Q000473:pathology / Q000648:ultrastructure; D005808:Genes, Recessive / Q000235:genetics; D018740:Genetic Heterogeneity; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008854:Microscopy, Electron; D009154:Mutation; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D011859:Radiography; D017384:Sequence Deletion; D013577:Syndrome
C477370:DYM protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins