Distal arthrogryposis with variable clinical expression caused by TNNI2 mutation.

Area of Science:

• Genetics
• Molecular Biology
• Clinical Medicine

Background:

• Distal arthrogryposis (DA) is a group of congenital disorders characterized by multiple joint contractures.
• DA exhibits significant clinical and genetic heterogeneity, making diagnosis and understanding of its mechanisms challenging.

Purpose of the Study:

• To identify the genetic cause of distal arthrogryposis in a patient presenting with hand and foot deformities and torticollis.
• To investigate the role of the TNNI2 gene in the pathogenesis of DA.

Main Methods:

• Whole exome sequencing was performed to identify genetic variants in the affected patient.
• Segregation analysis was conducted to confirm the identified mutation in family members.

Main Results:

• A novel mutation, c.485G>A (p.Arg162Lys), in the TNNI2 gene was identified in the patient and her father.
• The patient exhibited typical features of distal arthrogryposis, while her father presented with hip dysplasia, indicating variable clinical expression.

Conclusions:

• The identified TNNI2 mutation is likely responsible for the observed distal arthrogryposis phenotype in this family.
• This finding expands the known genetic spectrum of DA2B and underscores the importance of considering variable expressivity in genetic disorders.