Cutis Laxa via the LTBP4 Gene

LTBP4-related Cutis laxa is characterized by skin laxity, bronchopulmonary dysplasia, gastrointestinal/urinary malformations, pulmonary artery stenosis, dysmorphic facial features, joint laxity and postnatal growth delay. Dysmorphic facial features include hypertelorism, microretrognathia, long philtrum and wide fontanelles (Urban et al. 2009).

Pathogenic variants in the LTBP4 gene cause autosomal recessive cutis laxa type IC. LTBP4 protein stands for latent transforming growth factor betas (TGFbs) binding protein 4, which modulates the activity of TGFbs (Oklü and Hesketh 2000). To date, more than 10 unique pathogenic LTBP4 pathogenic variants have been reported. They are: missense (19%), nonsense (38%), truncating (38%), and splicing (5%) (Callewaert et al. 2013; Human Gene Mutation Database). No large deletions or duplications have been reported.

In one study, LTBP4 pathogenic variants were identified in 9 out of 12 studied families with cutis laxa (Callewaert B et al. 2013). Mutation detection rate should be high because all reported LTBP4 pathogenic variants are missense or nonsense/truncating pathogenic variants which can be detected by sequence analysis.

This test provides full coverage of all coding exons of the LTBP4 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).