Carriers with functional null mutations in LAMA3 have localized enamel abnormalities due to haploinsufficiency

Katarzyna B. Gostynska*, Wing Yan Yuen, Anna Maria Gerdina Pasmooij, Cornelius Stellingsma, Hendri H. Pas, Henny Lemmink, Marcel F. Jonkman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)

Abstract

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 alpha 3 chain (haploinsufficiency).

Original languageEnglish
Pages (from-to)94-99
Number of pages6
JournalEuropean Journal of Human Genetics
Volume25
DOIs
Publication statusPublished - 2017

Keywords

  • JUNCTIONAL EPIDERMOLYSIS-BULLOSA
  • AMELOGENESIS IMPERFECTA
  • DIAGNOSIS
  • LAMB3
  • EXPRESSION
  • DISORDERS
  • DEFECTS
  • BP180

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