Screening of the <i>FANCA</i> gene mutational hotspots in the Pakistani fanconi anemia patients revealed 19 sequence variations

• Muhammad Shahid

  Department of Animal Sciences, Faculty of Biological Sciences Quaid‐i‐Azam University Islamabad Pakistan

• Sabika Firasat

  Department of Animal Sciences, Faculty of Biological Sciences Quaid‐i‐Azam University Islamabad Pakistan

• Humayoon Shafique Satti

  Armed Forces Bone Marrow Transplant Centre (AFBMTC), CMH Medical Complex Rawalpindi Pakistan

• Tariq Mahmood Satti

  Armed Forces Bone Marrow Transplant Centre (AFBMTC), CMH Medical Complex Rawalpindi Pakistan

• Tariq Ghafoor

  Armed Forces Bone Marrow Transplant Centre (AFBMTC), CMH Medical Complex Rawalpindi Pakistan

• Imtenan Sharif

  Department of Community Medicine, Army Medical College (AMC), National University of Medical Sciences Rawalpindi Pakistan

• Kiran Afshan

  Department of Animal Sciences, Faculty of Biological Sciences Quaid‐i‐Azam University Islamabad Pakistan

抄録

Fanconi anemia (FA) is a recessive disorder that predispose to bone marrow failure and multiple congenital anomalies in affected individuals worldwide. To date, 22 FA genes are known to harbor sequence variations in disease phenotype. Among these, mutations in the FANCA gene are associated with 60% to 70% of FA cases. The aim of the present study was to screen FA cases belonging to consanguineous Pakistani families for selected exons of FANCA gene which are known mutational hotspots for Asian populations. Blood samples were collected from 20 FA cases and 20 controls. RNA was extracted and cDNA was synthesized from blood samples of cases. DNA was extracted from blood samples of cases and ethnically matched healthy controls. Sanger's sequencing of the nine selected exons of FANCA gene in FA cases revealed 19 genetic alterations of which 15 were single nucleotide variants, three were insertions and one was microdeletion. Of the total 19 sequence changes, 13 were novel and six were previously reported. All identified variants were evaluated by computational programs including SIFT, PolyPhen‐2 and Mutation taster. Seven out of 20 analyzed patients were carrying homozygous novel sequence variations, predicted to be associated with FA. These disease associated novel variants were not detected in ethnically matched controls and depict genetic heterogeneity of disease.

収録刊行物

• Congenital Anomalies

  Congenital Anomalies 60 (1), 32-39, 2019-03-24

  Wiley

キーワード

• Developmental Biology
• Embryology
• General Medicine
• Pediatrics, Perinatology and Child Health

詳細情報

• CRID: 1360284921347621248
• NII論文ID: 210000012757
• DOI: 10.1111/cga.12331
• ISSN: 17414520
• ISSN: 09143505
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fcga.12331
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1111/cga.12331
• Web Site: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cga.12331
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