Sequence Variants in MEGF8 and GJA1 Underlying Syndactyly

Area of Science:

• Medical Genetics
• Developmental Biology
• Congenital Malformations

Background:

• Syndactyly is a common congenital limb malformation resulting from failed digit separation during embryonic development.
• It affects approximately 1 in 2,500-3,000 live births and can exhibit familial inheritance patterns.

Purpose of the Study:

• To identify the genetic basis of severe syndactyly in two unrelated families.
• To expand the understanding of genetic mutations associated with syndactyly.

Main Methods:

• Whole-exome sequencing was performed on Family A, which presented with autosomal recessive syndactyly.
• Candidate gene sequencing was utilized for Family B, exhibiting autosomal dominant syndactyly.

Main Results:

• Two novel missense variants were discovered: p.(Cys1925Arg) in the MEGF8 gene in Family A.
• A novel missense variant, p.(Thr89Ile), was identified in the GJA1 gene in Family B.

Conclusions:

• The identified novel variants in MEGF8 and GJA1 expand the known mutation spectrum for syndactyly.
• These findings aid in screening Pakistani families with similar clinical features and contribute to understanding syndactyly genetics.