Title : Novel mutations in PDE6A and CDHR1 cause retinitis pigmentosa in Pakistani families
Abstract:
Background: A series of inherited illnesses known as retinitis pigmentosa are clinically and genetically diverse and are characterized by a progressive loss of photoreceptor and pigment epithelial function. Retinitis pigmentosa is one of the most prevalent causes of vision impairment in all age groups, with a prevalence of between 1300 and 1500. The aims of the current study were to investigate the genetic basis of autosomal recessive retinitis pigmentosa (arRP) in two consanguineous/ endogamous Pakistani families.
Methodology: Whole exome sequencing (WES) was performed on genomic DNA samples of patients with arRP to identify disease causing mutations. Sanger sequencing was performed to confirm familial segregation of identified mutations, and potential pathogenicity was determined by predictions of the mutations’ functions.
Results: A novel homozygous frameshift mutation [NM_000440.2:c.1054delG, p. (Gln352Argfs*4); Chr5:g.149286886del (GRCh37)] in the PDE6A gene in an endogamous family and a novel homozygous splice site mutation[NM_033100.3:c.1168-1G>A, Chr10:g.85968484G>A (GRCh37)] in the CDHR1 gene in a consanguineous family were identified. The PDE6A variant p. (Gln352Argfs*4) was predicted to be deleterious or pathogenic, whilst the CDHR1 variant c.1168-1G>A was predicted to result in potential alteration of splicing.
