Amelogenesis Imperfecta, Type If

A number sign (#) is used with this entry because of evidence that amelogenesis imperfecta type IF (AI1F) is caused by homozygous mutation in the ameloblastin gene (AMBN; 601259) on chromosome 4q13.

Description

Amelogenesis imperfecta type IF is characterized by hypoplastic enamel of the primary and secondary dentition. The teeth may appear rough and discolored, and the tooth enamel may be absent, pitted, or of varying thickness (Poulter et al. (2014)).

Clinical Features

Poulter et al. (2014) described a consanguineous Costa Rican family with generalized hypoplastic amelogenesis imperfecta involving the primary and secondary dentitions. Clinical examination of the 3 affected sisters revealed enamel that was hard, but discolored and rough. Poulter et al. (2014) examined 5 deciduous teeth retained by the family after natural exfoliation and noted that the enamel was pitted and varied in thickness over the crown from near normal in some areas to absent altogether. Scanning electron microscopy of thicker areas of enamel on affected teeth showed abnormal prismatic structure.

Prasad et al. (2016) reported 2 sisters with isolated hypoplastic amelogenesis imperfecta identified through screening of a large cohort of orodental patients from clinics in France, Germany, and Morocco. The authors stated that the very limited enamel in these patients was similar to that in the patients reported by Poulter et al. (2014) but that the tooth surfaces did not seem as pitted. No additional clinical details were provided.

Inheritance

The transmission pattern of amelogenesis imperfecta in the family reported by Poulter et al. (2014) was consistent with autosomal recessive inheritance.

Mapping

By SNP microarray analysis in a family segregating autosomal recessive amelogenesis imperfecta, Poulter et al. (2014) identified 2 shared regions of homozygosity on chromosomes 1p and 4q.

Molecular Genetics

By exome sequencing in 3 sisters with hypoplastic amelogenesis imperfecta from a consanguineous Costa Rican family, Poulter et al. (2014) identified a homozygous 2,347-bp deletion in the AMBN gene (601259.0001), encompassing all 237 basepairs of exon 6 and 2,110 basepairs of flanking sequence on either side of the exon. The deletion was predicted to create an in-frame deletion of 79 amino acids (Tyr99_Glu177del), shortening the protein from 447 to 368 amino acids. No functional studies were performed; however, the human phenotype was noted to be similar to the Ambn-null mouse model. A screen of 13 additional hypoplastic AI families revealed no further mutations.

In 2 sisters with AI1F, Prasad et al. (2016) identified a homozygous splice site mutation in the AMBN gene (601259.0002).