Ghazanfar Ali1, Jia Nee Foo2,3, Abdul Nasir4, Chu-Hua Chang2,3, Elaine GuoYan Chew2,3, Zahid Latif5, Zahid Azeem6, Syeda Ain-Ul-Batool1, Syed Akif Raza Kazmi7, Naheed Bashir Awan1, Abdul Hameed Khan1, Fazal-Ur- Rehman8, Madiha Khalid1,9, Abdul Wali10, Samina Sarwar5, Wasim Akhtar11, Ansar Ahmed Abbasi12, Rameez Nisar12. 1. Department of Biotechnology, University of Azad Jammu and Kashmir, P.O. Box 13100, Muzaffarabad, Pakistan. 2. Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232. 3. Human Genetics, Genome Institute of Singapore, A∗STAR, 60 Biopolis Street, Singapore 138672. 4. Molecular Science and Technology, Ajou University, Suwon, Republic of Korea. 5. Department of Zoology, University of Azad Jammu and Kashmir, P.O. Box 13100, Muzaffarabad, Pakistan. 6. Department of Biochemistry/Molecular Biology AJK Medical College, Muzaffarabad, Pakistan. 7. Department of Chemistry Government College University Lahore, Pakistan. 8. Department of Microbiology, Faculty of Life Sciences, University of Balochistan, Quetta, Pakistan. 9. Department of Biotechnology, Women University of Azad Kashmir Bagh, 12500, Pakistan. 10. Department of Biotechnology, Faculty of Life Sciences and Informatics, BUITEMS, 87100 Quetta, Pakistan. 11. Department of Botany, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan. 12. Department of Zoology, Mirpur University of Science and Technology (MUST), Mirpur AJK, Pakistan.
Abstract
BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive inherited disorder with distinctive clinical feature such as obesity, degeneration of retina, polydactyly, and renal abnormalities. The study was aimed at finding out the disease-causing variant/s in patients exhibiting clinical features of BBS. METHODS: The identification of disease-causing variant was done by using whole exome sequencing on Illumina HiSeq 4000 platform involving the SeqCap EZ Exome v3 kit (Roche NimbleGen). The identified variant was further validated by Sanger sequencing. RESULTS: WES revealed a novel homozygous missense mutation (NM_031885: c.443A>T:p.N148I) in exon 3 of the BBS2 gene. Sanger sequencing confirmed this variant as homozygous in both affected subjects and heterozygous in obligate parents, demonstrating autosomal recessive inheritance pattern. To the best of our knowledge, this variant was not present in literature and all publically available databases. The candidate variant is predicted to be pathogenic by a set of in-silico softwares. CONCLUSION: Clinical and genetic spectrum of BBS and BBS-like disorders is not completely defined in the Pakistani as well as in Kashmiri population. Therefore, more comprehensive genetic studies are required to gain insights into genotype-phenotype associations to facilitate carrier screening and genetic counseling of families with such disorders.
BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive inherited disorder with distinctive clinical feature such as obesity, degeneration of retina, polydactyly, and renal abnormalities. The study was aimed at finding out the disease-causing variant/s in patients exhibiting clinical features of BBS. METHODS: The identification of disease-causing variant was done by using whole exome sequencing on Illumina HiSeq 4000 platform involving the SeqCap EZ Exome v3 kit (Roche NimbleGen). The identified variant was further validated by Sanger sequencing. RESULTS: WES revealed a novel homozygous missense mutation (NM_031885: c.443A>T:p.N148I) in exon 3 of the BBS2 gene. Sanger sequencing confirmed this variant as homozygous in both affected subjects and heterozygous in obligate parents, demonstrating autosomal recessive inheritance pattern. To the best of our knowledge, this variant was not present in literature and all publically available databases. The candidate variant is predicted to be pathogenic by a set of in-silico softwares. CONCLUSION: Clinical and genetic spectrum of BBS and BBS-like disorders is not completely defined in the Pakistani as well as in Kashmiri population. Therefore, more comprehensive genetic studies are required to gain insights into genotype-phenotype associations to facilitate carrier screening and genetic counseling of families with such disorders.
Authors: Veronika Niederlova; Martin Modrak; Oksana Tsyklauri; Martina Huranova; Ondrej Stepanek Journal: Hum Mutat Date: 2019-07-29 Impact factor: 4.878
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Authors: Muhammad Muzammal; Muhammad Zubair; Sophie Bierbaumer; Jasmin Blatterer; Ricarda Graf; Aisha Gul; Safdar Abbas; Muhammad Badar; Ansar Ahmad Abbasi; Muzammil Ahmad Khan; Christian Windpassinger Journal: Mol Genet Genomic Med Date: 2019-07-11 Impact factor: 2.183