A New Intronic Variant in ECEL1 in Two Patients with Distal Arthrogryposis Type 5D

Area of Science:

• Genetics
• Molecular Biology
• Clinical Medicine

Background:

• Distal Arthrogryposis type 5D (DA5D) is an autosomal recessive disorder.
• DA5D presents with congenital contractures, short stature, scoliosis, ptosis, astigmatism, and dysmorphic features.
• Pathogenic variants in the ECEL1 gene are known causes of DA5D.

Observation:

• Two unrelated patients of Sardinian origin with DA5D were analyzed.
• A novel homozygous intronic variant (c.1507-9G>A) in the ECEL1 gene was identified in both patients.
• This variant is predicted to disrupt mRNA splicing by activating a cryptic splice site.

Findings:

• The identified ECEL1 variant (c.1507-9G>A) represents a new cause of Distal Arthrogryposis type 5D.
• The variant's low frequency in the general population suggests a founder effect in the Sardinian cohort.
• This discovery expands the known spectrum of ECEL1 mutations to include noncoding variants affecting splicing.

Implications:

• This finding contributes to a better understanding of the genetic basis of DA5D.
• It highlights the importance of investigating intronic regions for novel pathogenic variants.
• The identification of this variant aids in genetic counseling and diagnosis for families with DA5D.