Novel KIAA0825 Variants Underlie Nonsyndromic Postaxial Polydactyly

Area of Science:

• Genetics
• Human Physiology
• Developmental Biology

Background:

• Polydactyly, characterized by extra digits, is a common congenital condition.
• Twelve genes are known to cause nonsyndromic polydactyly, with KIAA0825 being one of them.

Purpose of the Study:

• To investigate the genetic basis of nonsyndromic postaxial polydactyly (PAP) in Pakistani families.
• To identify novel genetic variants associated with autosomal recessive PAP.

Main Methods:

• Clinical and genetic evaluation of four consanguineous Pakistani families with PAP.
• Utilized exome sequencing and/or microsatellite marker genotyping followed by Sanger sequencing.

Main Results:

• Identified three novel KIAA0825 variants segregating with PAP: a nonsense variant (p.(Trp773*)), a missense variant (p.(Val324Phe)), and an in-frame deletion (p.(Gln915_Val918del)).
• The nonsense variant was linked to PAP type B (PAPB), while the missense and deletion variants were associated with both PAP type A and B.

Conclusions:

• Expanded the clinical and genetic spectrum of PAP caused by KIAA0825 variants.
• Reported the first KIAA0825 variant exclusively associated with PAP type B.