Molecular Diagnosis of Rare Autosomal Recessive Escobar Syndrome in a Consanguineous Pakistani Family.

Escobar syndrome, a nonlethal variant of multiple pterygium syndromes (MPS), is a rare autosomal recessive disorder characterized by pterygia and multiple joint contractures along with other anomalies. Variants in cholinergic receptor nicotinic gamma subunit () have been previously reported in patients with Escobar syndrome. We studied a consanguineous Pakistani family affected with Escobar syndrome to identify the underlying genetic defect through short tandem repeat (STR) genotyping and direct DNA sequencing. Genotyping with microsatellite markers (D2S427, D2S2344, and D2S206) revealed linkage of the disease phenotype in the family to the locus. Using Sanger sequencing, we identified a homozygous nonsense variant c.136C>T (p.R46*), predicted to produce a truncated protein that leads to acetylcholine receptor deficiency, causing MPS. The unaffected parents and siblings in the family were heterozygous carriers of this disease-causing variant. We report the identification of a nonsense variant in a consanguineous Pakistani family affected with Escobar syndrome.