A Novel ECEL1 Variant Associated with a Congenital Contracture Disorder

A consanguineous Pakistani family with three affected siblings was investigated to determine the genetic diagnosis of an inherited contracture disorder. Whole-exome sequencing was performed for four participants. Variants were filtered based on homozygosity in the three patients and heterozygosity in the obligate carrier (mother), predicted effect of variants on the encoded protein, and their frequencies in public databases. Sanger sequencing was performed to explore the segregation of the variant with the phenotype. All patients had congenital limb contractures. These included camptodactyly of hands and feet, ptosis, adducted thumb and clubfoot morphology. A novel homozygous missense variant in ECEL1 c.2051A>G, p.(Tyr684Cys) was identified in all three patients. The variant was absent from the DNA of 500 ethnically matched control samples as well as from all public databases. In conclusion, this study reports a family with clinical features of distal arthrogryposis type 5D and extends the genotype spectrum of the disorder.

Automated summary

This study investigated a consanguineous Pakistani family with three affected siblings to determine the genetic diagnosis of an inherited contracture disorder. Whole-exome sequencing and Sanger sequencing were performed to identify a novel homozygous missense variant in ECEL1 gene, which was absent from control samples and public databases. The study reports a family with clinical features of distal arthrogryposis type 5D and extends the genotype spectrum of the disorder.