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.
Hellemans
Jan
J
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Debeer
Philippe
P
Wright
Michael
M
Janecke
Andreas
A
Kjaer
Klaus W
KW
Verdonk
Peter C M
PC
Savarirayan
Ravi
R
Basel
Lina
L
Moss
Celia
C
Roth
Johannes
J
David
Albert
A
De Paepe
Anne
A
Coucke
Paul
P
Mortier
Geert R
GR
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