Sequence Variants in the WNT10B Underlying Non-Syndromic Split-Hand/Foot Malformation

Area of Science:

• Genetics
• Developmental Biology
• Medical Genetics

Background:

• Split Hand and Foot Malformation (SHFM), also known as ectrodactyly, is a rare limb malformation.
• SHFM is characterized by median clefts in the hands and feet due to impaired or absent central ray development.
• It can manifest as an isolated condition or alongside other developmental abnormalities.

Purpose of the Study:

• To identify the genetic cause of non-syndromic SHFM in two families.
• To investigate the role of WNT10B gene variants in limb development disorders.

Main Methods:

• Clinical phenotyping of two families with non-syndromic SHFM.
• Whole exome sequencing and Sanger sequencing to detect causative genetic variants.

Main Results:

• Two pathogenic variants in the WNT10B gene were identified in affected individuals from both families.
• A novel missense variant (c.338G>C; p.(Gly113Ala)) was found in Family A.
• A previously reported frameshift variant (c.884-896delTCCAGCCCCGTCT; p.(Phe295Cysfs*87)) was identified in Family B.

Conclusions:

• The study identifies a novel WNT10B variant as a cause of SHFM.
• These findings expand the understanding of the genetic basis of SHFM and limb development.
• The results offer insights into the molecular mechanisms underlying limb malformations.