Amelogenesis imperfecta (AI; MIM 104530) is a heterogeneous collection of disorders encompassing inherited congenital defects of dental enamel formation, causing variably small, discolored, pitted, grooved, or fragile primary or permanent teeth. At least 14 syndromic and non-syndromic AI subtypes have been described, including autosomal dominant and recessive, and X-linked recessive. Gene mutations that underlie both the non-syndromic forms and the tricho-dento-osseous (MIM 190320) and Jalili syndromes (MIM 217080) have recently been described.1

After obtaining informed consent, we undertook a genome-wide scan on 16 family members using the Affymetrix 10K SNP. Haplotypes, or clusters of SNPs that tend to be inherited together, were inferred from the data by Genespring GT (Agilent Software). Initial analysis included genome-wide autozygosity mapping to identify regions identical by descent that were shared among affected individuals, and parametric linkage analysis assuming a recessive mode of inheritance with 100% penetrance and a disease allele frequency of 0.001. We identified an 11-Mb region of excess homozygozity shared among affected individuals on chromosome 17 (autozygozity logarithm of the odds (LOD)=6.53). Microsatellite markers spanning this region were then used to genotype all family members. Key recombination events were detected between markers D17S807 and D17S1821, and D17S1786 and D17S949 (Figure 1b), which allowed the linkage interval to be narrowed to 3.69 Mb. This region contains 34 genes.

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