Dental Anomalies and Amelogenesis Imperfecta via the LTBP3 Gene

Dental anomalies and short stature is a skeletal dysplasia characterized by amelogenesis imperfecta and platyspondyly. Patients usually have enamel hypoplasia, short trunk and brachyolmia-like anomalies. Other features include missing teeth, widely spaced teeth, delayed eruption permanent teeth, missing permanent teeth, and enlarged pulp chamber.

Pathogenic variants in the LTBP3 gene cause autosomal recessive Dental Anomalies and Short Stature (Huckert et al. 2015), as well as autosomal recessive Oligodontia (Noor et al. 2009). LTBP3 protein stands for the latent transforming growth factor betas (TGFbs) binding protein 3, an extracellular matrix protein, which modulates the activity of TGFbs. To date, less than 10 unique pathogenic LTBP3 pathogenic variants have been reported. They are: missense (1), nonsense (1) truncating (4) and splicing (1) (Huckert et al. 2015; Human Gene Mutation Database). No large deletions/duplications have been reported.

Clinical sensitivity is currently unknown due to limitations in the medical literature. Analytical sensitivity may be high because all reported pathogenic variants are expected to be detected by sequencing.

This test provides full coverage of all coding exons of the LTBP3 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).