Arthrogryposis multiplex congenital (AMC) relates to congenital joint contractures or motion limitations affecting numerous regions of the body. Its prevalence is between 1/3000 and 1/5000 babies born alive in association with various distinct conditions, generally as a result of fetal akinesia. Distal arthrogryposis type 5D (DA5D) is the only distal arthrogryposis type transmitted in an autosomal recessive manner, and it is distinguished by severe camptodactyly of the hands and wrists, milder camptodactyly of the toes, restricted knee flexing, talus or varus deformity of the ankles, short height, scoliosis, etc. It is predominantly caused by homozygous or compound heterozygous variants in the ECEL1 gene.
Alesi, et al. (2021, PMID: 33672664) analyzed 2 distal arthrogryposis type 5D patients by exome sequencing, as well as their parents with Sanger sequencing. Geneyx Analysis was then used to identify the candidate variants.
Through using Geneyx Analysis, the authors were able to correctly call the homozygous causative ECEL1 c.1507-9G>A variant in both patients. Interestingly the variant identified had a low frequency in the human population (MAF 0.00004), had not been previously observed in a homozygous state, and is interpreted as an uncertain significance variant according to ACMG guidelines. This leads to a novel finding, with supporting evidence including the patient’s clinical presentations and the segregation data within the families. Together, Geneyx Analysis is fundamental in identifying novel mutations and can be used to effectively correlate causative relationships with rare disorders.