Novel mutations in PDE6A and CDHR1 cause retinitis pigmentosa in Pakistani families
Authors:   Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan, Dawood Muhammad , Din Taj Ud ,   Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan, Shah Irfan Ullah ,   Department of Ophthalmology, KMU Institute of Medical Sciences (KIMS) Kohat 26000, Khyber Pakhtunkhwa, Pakistan, Khan Niamat ,   Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan, Jan Abid ,   Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan, Marwan Muhammad ,   Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan, Sultan Komal ,   Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan, Nowshid Maha ,   Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan, Tahir Raheel ,   Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan, Ahmed Asif Naveed ,   Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan, Yasin Muhammad ,   Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan, Baple Emma L. ,   Medical Research, RILD Wellcome Wolfson Centre (Level 4), Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon EX2 5DW, UK, Crosby Andrew H. ,   Medical Research, RILD Wellcome Wolfson Centre (Level 4), Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon EX2 5DW, UK, Saleha Shamim ,   Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan
Published: November 2021

AIM: To investigate the genetic basis of autosomal recessive retinitis pigmentosa (arRP) in two consanguineous/ endogamous Pakistani families.
METHODS: 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.
CONCLUSION: This study expands the spectrum of genetic variants for arRP in Pakistani families.