Identification of two novel ATP6V0A2 mutations in an infant with cutis laxa by exome sequencing

Cutis laxa (CL) refers to a group of rare connective tissue disorders challenging to diagnose because of their different inheritance pattern, extensive phenotypic variability, and genetic heterogeneity. In this study, we performed whole exome sequencing of an Italian seven-month-old infant with generalized, sagging, redundant skin cutis laxa type, delayed fontanelle closure, borderline microcephaly, dysmorphisms, and without current neurological involvement. Bioinformatics filtering of the variants in known CL genes allowed the identification of two novel loss-of-function mutations in the ATP6V0A2 gene, leading to the diagnosis of autosomal recessive CL type 2A (ARCL2A). Segregation analysis by Sanger sequencing revealed that the c.534delC and c.1002delT small deletions were inherited from the unaffected father and mother, respectively. Our molecular findings, obtained through the powerful exome sequencing approach, expand the knowledge of the clinical phenotype and the allelic repertoire of ARCL2A.