SHORT REPORT

Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel defects

T C Hart¹, P S Hart², M C Gorry³, M D Michalec⁴, O H Ryu⁵, C Uygur⁶, D Ozdemir⁷, S Firatli⁸, G Aren⁹, E Firatli¹⁰

¹ Department of Oral Medicine and Pathology, School of Dental Medicine and Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
² Department of Human Genetics, School of Public Health, University of Pittsburgh
³ Department of Oral Medicine and Pathology, School of Dental Medicine, University of Pittsburgh
⁴ Department of Human Genetics, School of Public Health, University of Pittsburgh
⁵ Department of Oral Medicine and Pathology, School of Dental Medicine, University of Pittsburgh
⁶ Department of Periodontology, School of Dentistry, University of Istanbul, Istanbul, Turkey
⁷ Department of Pedodontics, School of Dentistry, University of Istanbul
⁸ Department of Orthodontics, School of Dentistry, University of Istanbul
⁹ Department of Pedodontics, School of Dentistry, University of Istanbul
¹⁰ Department of Periodontology, School of Dentistry, University of Istanbul

Correspondence to:
Correspondence to:
Dr Thomas C Hart
National Institutes of Health, NIDCR, Building 10, Room 1N–117, 10 Center Drive, Bethesda, MD 20892, USA; thart{at}mail.nih.gov

The genetic basis of non-syndromic autosomal recessive forms of amelogenesis imperfecta (AI) is unknown. To evaluate five candidate genes for an aetiological role in AI. In this study 20 consanguineous families with AI were identified in whom probands suggested autosomal recessive transmission. Family members were genotyped for genetic markers spanning five candidate genes: AMBN and ENAM (4q13.3), TUFT1 (1q21), MMP20 (11q22.3–q23), and KLK4 (19q13). Genotype data were evaluated to identify homozygosity in affected individuals. Mutational analysis was by genomic sequencing. Homozygosity linkage studies were consistent for localisation of an AI locus in three families to the chromosome 4q region containing the ENAM gene. ENAM sequence analysis in families identified a 2 bp insertion mutation that introduced a premature stop codon in exon 10. All three probands were homozygous for the same g.13185_13186insAG mutation. These probands presented with a generalised hypoplastic AI phenotype and a class II openbite malocclusion. All heterozygous carriers of the g.13185_13186insAG mutation had localised hypoplastic enamel pitting defects, but none had AI or openbite. The phenotype associated with the g.13185_13186insAG ENAM mutation is dose dependent such that ARAI with openbite malocclusion segregates as a recessive trait, and enamel pitting as a dominant trait.

Keywords: enamelin; amelogenesis imperfecta; genetic heterogeneity; enamel pitting

Abbreviations: ADAI, autosomal dominant amelogenesis imperfecta; AI, amelogenesis imperfecta; ARAI, autosomal recessive amelogenesis imperfecta; LHED, localised hypoplastic enamel defects; SNP, single nucleotide polymorphism; STRP, short tandem repeat polymorphism

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