Carriers with functional null mutations in LAMA3 have localized enamel abnormalities due to haploinsufficiency.
The hereditary blistering disease junctional epidermolysis bullosa (JEB) is always accompanied by structural enamel abnormalities of primary and secondary dentition, characterized as amelogenesis imperfecta. Autosomal recessive mutations in LAMA3, LAMB3 and LAMC2 encoding the heterotrimer laminin 332 (LM-332) are among the genes causing JEB. While examining pedigrees of JEB patients with LAMA3 mutations, we observed that heterozygous carriers of functional null mutations displayed subtle enamel pitting in the absence of skin fragility or other JEB symptoms. Here, we report two new LAMA3 functional null mutations: nonsense c.2377C>T p.(Arg793Ter) and splice-site c.4684+1G>A mutation in heterozygous carriers exhibiting enamel pitting. Both parents had offspring affected with JEB and displayed subtle enamel pitting of secondary dentition without any sign of skin blistering. The reported enamel abnormality in LAMA3 mutation carriers could be attributed to a half dose effect of the laminin α3 chain (haploinsufficiency).
Departments of Dermatology, Center for Blistering Diseases, Groningen, The Netherlands. k.gostynska@umcg.nl.
Katarzyna B
KB
Gostyńska
Departments of Dermatology, Center for Blistering Diseases, Groningen, The Netherlands.
Wing
W
Yan Yuen
Departments of Dermatology, Center for Blistering Diseases, Groningen, The Netherlands.
Anna Maria Gerdina
AMG
Pasmooij
Oral and Maxillofacial Surgery and Maxillofacial Prosthetics Genetics, Groningen, The Netherlands.
Cornelius
C
Stellingsma
Departments of Dermatology, Center for Blistering Diseases, Groningen, The Netherlands.
Hendri H
HH
Pas
University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Henny
H
Lemmink
Departments of Dermatology, Center for Blistering Diseases, Groningen, The Netherlands.
Marcel F
MF
Jonkman
D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D003743:Dental Enamel / Q000473:pathology; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics* / Q000473:pathology; D005260:Female; D057895:Haploinsufficiency / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007797:Laminin / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree
D018389:Codon, Nonsense; D007797:Laminin; C095567:laminin alpha 3