Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia Telangiectasia
Introduction. Ataxia telangiectasia is a rare genetic condition with an estimated prevalence of 1 in 40,000–100,000 live births. This condition predominantly affects the nervous and immune systems. It is characterized by progressive ataxia beginning from early childhood. The neurological deficit ass...
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| Format: | Article |
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Wiley
2020-01-01
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| Series: | Case Reports in Genetics |
| Online Access: | http://dx.doi.org/10.1155/2020/6630300 |
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| author | D. Hettiarachchi Hetalkumar Panchal B. A. P. S. Pathirana P. D. Rathnayaka A. Padeniya P. S. Lai V. H. W. Dissanayake |
| author_facet | D. Hettiarachchi Hetalkumar Panchal B. A. P. S. Pathirana P. D. Rathnayaka A. Padeniya P. S. Lai V. H. W. Dissanayake |
| author_sort | D. Hettiarachchi |
| collection | DOAJ |
| description | Introduction. Ataxia telangiectasia is a rare genetic condition with an estimated prevalence of 1 in 40,000–100,000 live births. This condition predominantly affects the nervous and immune systems. It is characterized by progressive ataxia beginning from early childhood. The neurological deficit associated with this condition affects one’s balance, coordination, walking, and speech and can be accompanied by chorea, myoclonus, and neuropathy. They may also have ocular telangiectasias and high levels of blood alpha-fetoprotein (AFP). The ataxia telangiectasia mutated gene (ATM) is associated with this condition and codes for the ATM protein which is a phosphatidylinositol 3-kinase. This gene occupies 150 kb on chromosome 11q22–23 and contains 66 exons encoding a 13 kb transcript. ATM is a relatively large protein with a molecular weight of 350 kDa and 3,056 amino acids. Methods. Four patients of Sri Lankan origin presenting with features suggestive of ataxia telangiectasia were referred to our genetics center for specialized genetic counseling and testing. Whole-exome sequencing followed by Sanger sequencing was used to confirm the candidate variants. Protein modeling and genotype to phenotype correlation was performed in the identified variants. Results. We observed 6 novel ATM gene variants in four patients with ataxia telangiectasia. The identified variants are as follows: homozygous c.7397C > A (p.Ala2466Glu) and c.510_511delGT (p.Tyr171fs) and compound heterozygous c.5347_5350delGAAA (p.Glu1783fs), c.8137A > T (p.Arg2713∗) and c.1163A > C (p.Lys388Thr), and c.5227A > C (p.Thr1743Pro). Variant analysis was followed by modeling of the native and altered protein structures. Conclusion. We report novel ATM gene variants that have implications on the molecular diagnosis of ataxia telangiectasia. |
| format | Article |
| id | doaj-art-96286ec53a37456d84e95927ac71af37 |
| institution | Kabale University |
| issn | 2090-6544 2090-6552 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Genetics |
| spelling | doaj-art-96286ec53a37456d84e95927ac71af372025-02-03T06:05:39ZengWileyCase Reports in Genetics2090-65442090-65522020-01-01202010.1155/2020/66303006630300Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia TelangiectasiaD. Hettiarachchi0Hetalkumar Panchal1B. A. P. S. Pathirana2P. D. Rathnayaka3A. Padeniya4P. S. Lai5V. H. W. Dissanayake6Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri LankaPost Graduate Department of Bioscience, Sardar Patel University, Vallabh Vidyanagar, Gujarat, IndiaHuman Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri LankaLady Ridgway Hospital for Children, Colombo, Sri LankaLady Ridgway Hospital for Children, Colombo, Sri LankaDepartment of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeHuman Genetics Unit, Faculty of Medicine, University of Colombo, Colombo, Sri LankaIntroduction. Ataxia telangiectasia is a rare genetic condition with an estimated prevalence of 1 in 40,000–100,000 live births. This condition predominantly affects the nervous and immune systems. It is characterized by progressive ataxia beginning from early childhood. The neurological deficit associated with this condition affects one’s balance, coordination, walking, and speech and can be accompanied by chorea, myoclonus, and neuropathy. They may also have ocular telangiectasias and high levels of blood alpha-fetoprotein (AFP). The ataxia telangiectasia mutated gene (ATM) is associated with this condition and codes for the ATM protein which is a phosphatidylinositol 3-kinase. This gene occupies 150 kb on chromosome 11q22–23 and contains 66 exons encoding a 13 kb transcript. ATM is a relatively large protein with a molecular weight of 350 kDa and 3,056 amino acids. Methods. Four patients of Sri Lankan origin presenting with features suggestive of ataxia telangiectasia were referred to our genetics center for specialized genetic counseling and testing. Whole-exome sequencing followed by Sanger sequencing was used to confirm the candidate variants. Protein modeling and genotype to phenotype correlation was performed in the identified variants. Results. We observed 6 novel ATM gene variants in four patients with ataxia telangiectasia. The identified variants are as follows: homozygous c.7397C > A (p.Ala2466Glu) and c.510_511delGT (p.Tyr171fs) and compound heterozygous c.5347_5350delGAAA (p.Glu1783fs), c.8137A > T (p.Arg2713∗) and c.1163A > C (p.Lys388Thr), and c.5227A > C (p.Thr1743Pro). Variant analysis was followed by modeling of the native and altered protein structures. Conclusion. We report novel ATM gene variants that have implications on the molecular diagnosis of ataxia telangiectasia.http://dx.doi.org/10.1155/2020/6630300 |
| spellingShingle | D. Hettiarachchi Hetalkumar Panchal B. A. P. S. Pathirana P. D. Rathnayaka A. Padeniya P. S. Lai V. H. W. Dissanayake Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia Telangiectasia Case Reports in Genetics |
| title | Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia Telangiectasia |
| title_full | Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia Telangiectasia |
| title_fullStr | Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia Telangiectasia |
| title_full_unstemmed | Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia Telangiectasia |
| title_short | Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia Telangiectasia |
| title_sort | six novel atm gene variants in sri lankan patients with ataxia telangiectasia |
| url | http://dx.doi.org/10.1155/2020/6630300 |
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