Screening of exon 2 of ARL6 gene in a consanguineous Bardet Biedl Syndrome effected families from Khyber Pakhtunkhwa, Pakistan

Abstract

Laurence and Moon originally recognized the ciliopathy known as Bardet-Biedl (BBS) condition in 1866. By its primary and secondary characteristics, BBS syndrome can be identified. The main signs of BBS are rod/cone dystrophy (RCD), polydactyly (PD), obesity, gene defects, kidney abnormalities, and learning difficulties. Common BBS secondary symptoms include developmental delay, dental problems, heart defects, speech difficulties, syndactyly or brachydactyly, poor coordination, olfactory anomalies, diabetes mellitus, hypertension, liver disorders, and craniofacial dismorphism. Most people with polydactyly at birth appear healthy, but later in life they are diagnosed with BBS. The symptoms of BBS appear in relation to age; in early age only a few symptoms are obvious; other symptoms evolve after first decade of life. The prevalence of BBS varies in isolated, inbred, and consanguineous communities, where it is estimated to affect 1 in 150 000 persons worldwide. Numerous studies have that about 26 genes are implicated in the condition. Initial gene finding investigations for BBS syndrome showed autosomal recessive mode of inheritance, but subsequent study complicated the genetics of BBS and prevailed incomplete penetrance and triallelic inheritance. The most frequently altered genes in Pakistan and India are BBS10 and BBS3/ARL6. The purpose of the current studies was to study clinical characteristics of BBS cases and to identify the molecular causes of familial cases of Bardet-Biedl syndrome in local population. Ethical approval for this study was obtained from Bio-Ethical Committee of Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan, Hayatabad Medical Complex and Khyber Teaching Hospital, Peshawar, Pakistan. Ophthalmologists identified Retinitis Pigmentosa (RP) in all of the participating families, and following thorough interviewing, BBS families were selected. Blood samples and clinical records were collected from affected and unaffected members. For molecular genetic analysis, the genomic DNA was isolated. For the purpose of analyzing mutations, exon 2 of the ARL6 gene was amplified using primers. The amplified products were purified and sent for Sanger's sequencing. Sequence analysis did not show any polymorphism or mutation in the exon 2 of ARL6 gene in BBS identified families. To find a molecular genetic basis of disease, the remaining exons of ARL6 and other genes should be screened. The findings of this study also indicated that consanguinity is a factor in our population's high incidence that are recessively inherited, including BBS. Due of this, all participating families were provided with genetic counseling