Amelogenesis Imperfecta, Hypomaturation Type, Iia3


A number sign (#) is used with this entry because this form of hypomaturation amelogenesis imperfecta (AI) is caused by homozygous mutation in the WDR72 gene (613214).

For a phenotypic description and a discussion of genetic heterogeneity of the hypomaturation type of AI, see AI2A1 (204700).

Clinical Features

El-Sayed et al. (2009) studied 10 families with autosomal recessive hypomaturation amelogenesis imperfecta originating from Pakistan or Oman. The largest pedigree was Pakistani and had generalized AI with involvement of the primary and secondary dentitions. Radiographic appearance prior to eruption and clinical appearance upon eruption were consistent with near-normal enamel matrix volume formation; however, at the time of eruption, the enamel was creamier and more opaque than that of normal teeth. Once in the mouth, the enamel soon began to undergo posteruptive changes, including variable degrees of brown discoloration and loss of enamel tissue. In some instances enamel chipped away, but attrition was also evident. Variable malocclusions were observed, and 1 affected individual also had anterior open bite. Teeth were sensitive to thermal and physical stimuli. No other health problems segregated with AI.

Lee et al. (2010) described 2 families with hypomaturation amelogenesis imperfecta. The teeth in the 3 affected sisters in a Mexican family (family 1) had rough, stained enamel that deteriorated after eruption. The enamel layer displayed reduced radiodensity. The 2 affected brothers in a Turkish family (family 2) had a milder phenotype but the same reduced rediodensity of the enamel layer.


In a large Pakistani family segregating autosomal recessive AI, El-Sayed et al. (2009) identified a large region of homozygosity on chromosome 15; multipoint linkage analysis yielded a maximum lod score of 4.1 at D15S1016. Additional genotyping refined the locus to a 3-cM (4.4-Mb) interval on chromosome 15q21.3 between D15S1016 and D15S998, containing 16 annotated genes.

Molecular Genetics

In a large Pakistani family segregating autosomal recessive amelogenesis imperfecta mapping to chromosome 15q21.3, El-Sayed et al. (2009) sequenced 16 candidate genes and identified a nonsense mutation in the WDR72 gene (613214.0001). Analysis of the WDR72 gene in 4 Pakistani AI families and 5 Omani AI families revealed homozygosity for the same mutation in another Pakistani AI family with a similar clinical phenotype; in addition, 2 different WDR72 mutations were identified in 2 Omani AI families (613214.0002 and 613214.0003, respectively). The mutations all cosegregated consistently with the phenotype and were not found in controls. No mutations were detected in the 6 remaining AI families, indicating further genetic heterogeneity of hypomaturation AI.

By whole-exome sequencing of the WDR72 gene in a Mexican family and a Turkish family segregating autosomal recessive amelogenesis imperfecta, Lee et al. (2010) identified the same homozygous 2-bp deletion (c.1467_1468delAT; 613214.0004) that segregated with the disorder in both families.