Digitotalar dysmorphism: Molecular elucidation.

Area of Science:

• Genetics
• Molecular Biology
• Orthopedics

Background:

• Digitotalar dysmorphism (DTD) is an inherited condition causing limb abnormalities, including contractures and vertical talus.
• First described in 1972, DTD's molecular basis remained largely uncharacterized in the prototype South African family.

Purpose of the Study:

• To review clinical findings of DTD in the established family.
• To identify the specific genetic mutation causing DTD in this family.

Main Methods:

• Whole-exome next-generation sequencing was performed on DNA from an affected individual.
• Candidate gene analysis focused on known genes associated with distal arthrogryposes (DAs).
• Direct sequencing confirmed the identified mutation in affected family members.

Main Results:

• A pathogenic missense mutation, p.(Arg63His), was identified in exon nine of the TNNT3 gene.
• This mutation was confirmed in six affected family members.
• TNNT3 is implicated as a causative gene for DTD.

Conclusions:

• The study elucidates the molecular basis of DTD in the prototype family.
• Identifies a specific TNNT3 mutation responsible for the disorder.
• Contributes to understanding the genetic heterogeneity of distal arthrogryposes.