HOXA1 consists of two exons and one main domain called the Homeobox domain. Majority of the disease-causing variants found in this disease spectrum are truncating mutations (found in exon 1), which leads to the loss of function of HOXA1 protein. Additionally, missense variants are also reported. The two most common variants reported for ABDS and BSAS are c.76C>T p.Arg26Ter and c.175dup p.Val59GlyfsTer119 respectively in the homozygous state (The common mutation reported in these two populations from Saudi Arabia and Native Americans is attributed to genetic isolation due to high inbreeding and “genetic bottleneck” respectively). As HOXA1 is a small gene with only two exons, targeted gene testing of HOXA1 should be the first choice of the genetic test, provided the clinical features are suggestive of these diseases. If there are heterogeneous clinical features, then exome sequencing should be preferred.
HOXA1