Germline LEMD3 mutations are rare in sporadic patients with isolated melorheostosis.
To further explore the allelic heterogeneity within the group of LEMD3-related disorders, we have screened a larger series of patients including 5 probands with osteopoikilosis or Buschke-Ollendorff syndrome (BOS), 2 families with the co-occurrence of melorheostosis and BOS, and 12 unrelated patients with isolated melorheostosis. Seven novel LEMD3 mutations were identified, all predicted to result in loss-of-function of the protein. We confirm that loss-of-function mutations in the LEMD3 gene can result in either osteopoikilosis or BOS. However, LEMD3 germline mutations were only found in two melorheostosis patients belonging to a different BOS family and one sporadic patient with melorheostosis. The additional presence of osteopoikilosis lesions in these patients seemed to distinguish them from the group of sporadic melorheostosis patients where no germline LEMD3 mutation was identified. Somatic mosaicism for a LEMD3 mutation in the latter group was also not observed, and therefore we must conclude that the genetic defect in the majority of sporadic and isolated melorheostosis remains unknown.
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Jan
J
Hellemans
Philippe
P
Debeer
Michael
M
Wright
Andreas
A
Janecke
Klaus W
KW
Kjaer
Peter C M
PC
Verdonk
Ravi
R
Savarirayan
Lina
L
Basel
Celia
C
Moss
Johannes
J
Roth
Albert
A
David
Anne
A
De Paepe
Paul
P
Coucke
Geert R
GR
Mortier
D000483:Alleles; D001848:Bone Diseases, Developmental / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008557:Melorheostosis / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009030:Mosaicism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010023:Osteopoikilosis / Q000235:genetics*; D010375:Pedigree; D013577:Syndrome
D004268:DNA-Binding Proteins; C405329:LEMD3 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins