Exome sequence analysis in consanguineous Pakistani families inheriting Bardet‐Biedle syndrome determined founder effect of mutation c.299delC (p.Ser100Leufs*24) in BBS9 gene

Molecular Genetics & Genomic Medicine

Ansar Ahmad Abbasi¹  Muhammad Zubair²  Aisha Gul²  Muhammad Badar²  Muhammad Muzammal²  Safdar Abbas²  Muzammil Ahmad Khan²  Jasmin Blatterer³  Christian Windpassinger³  Sophie Bierbaumer³  Ricarda Graf³ 

[1] Department of Zoology Mirpur University of Science and Technology (MUST) Mirpur Pakistan;Gomal Centre of Biochemistry and Biotechnology Gomal University Dera Ismail Khan Pakistan;Institute of Human Genetics Medical University of Graz Graz Austria;

关键词: BBS9;    exome sequencing;    founder effect;    frameshift mutation;    Pakistani family;   

DOI  :  10.1002/mgg3.834

来源: DOAJ

【 摘 要 】

Abstract Background Bardet‐Biedl syndrome (BBS) is characterized by a heterogeneous phenotypic spectrum of retinopathy, intellectual disability (ID), obesity, polydactyly, and kidney dysfunctions as the major clinical features. Genetic investigations have reported 21 BBS genes, the products of which are mostly located at the centrosome, basal body or the ciliary transition zone. Methods In the present genetic report, we analyzed two apparently unrelated consanguineous BBS families from Dera Ismail Khan (D.I.Khan) district, Pakistan. Genetic mapping was performed using Whole exome sequencing and Sanger sequencing. Results Whole exome sequencing identified a recently reported single base deletion NM_001033604.1:c.299delC in the fourth exon of BBS9 in both families. The identified frameshift mutation is predicted to cause premature truncation of the expressed protein (p.Ser100Leufs*24). This mutation has previously been mapped in a consanguineous Pakistani family; therefore this is the second report of this particular mutation in two additional BBS families originating from different locations. Conclusion We speculate the evolutionary significance of this mutation and assume its strong founder effect in the Khaisoori tribe of D.I.Khan. Based on these findings, we suggest developing a molecular diagnostic test that may be used for premarital and prenatal screening of families at risk of BBS.

【 授权许可】

Unknown