Araştırma Makalesi
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Nadir Hastalıklarda WES Analizi ile Saptanan Genetik Varyantlar

Yıl 2023, Cilt: 45 Sayı: 1, 22 - 27, 23.01.2023
https://doi.org/10.20515/otd.1115008

Öz

Yeni nesil dizileme testleri, tıbbın çoğu alanında tanı sürecinin bir parçası haline gelmiştir. Özellikle tüm ekzom dizileme (WES) çalışmaları ile nadir kalıtsal hastalıklarda tanı oranı artmıştır. Bu çalışmada, hastalıklarının genetik kökenli olduğundan şüphelenilen 65 olgunun sonuçlarını klinik bulguları ile birlikte sunmayı amaçladık. Bursa Yüksek İhtisas Eğitim ve Araştırma Hastanesi Tıbbi Genetik Birimi'nde, 2016-2019 yılları arasında WES testi ile değerlendirilen hastalar retrospektif olarak taranarak analiz sonuçları ve klinik bulguları ile birlikte çalışmaya dahil edildi. Çalışmaya dahil edilen 65 olgunun 27'sinde (% 41.5) klinik bulgularıyla ilişkili 30 anlamlı varyant bulundu. Bu varyantların 20'si (% 66.7) daha önce literatürde bildirilmemişti. Fetustan 66 yaşına kadar geniş bir yaş aralığındaki hastalarda görülen nadir hastalıklar klinik bulguları ve WES sonuçları ile birlikte sunulmuştur. Sonuç olarak bu çalışma ile kalıtsal hastalıkların mutasyon spektrumuna katkıda bulunulmuştur.

Kaynakça

  • Bhatia NS, Lim JY, Bonnard C, et al. Singapore undiagnosed disease program: genomic analysis AIDS diagnosis and clinical management. SUREKids Working Group. Arch Dis Child 2021;106:31-37.
  • Bowdin S, Ray PN, Cohn RD, Meyn MS. The genome clinic: a multidisciplinary approach to assessing the opportunities and challenges of integrating genomic analysis into clinical care. Hum Mutat 2014;35:513-519.
  • Dixon-Salazar TJ, Silhavy JL, Udpa N, et al. Exome sequencing can improve diagnosis and alter patient management. Sci Transl Med 2012;4:138ra78.
  • Gorukmez O, Gorukmez O, Demiroren K. Novel PLVAP Mutation in Protein Losing Enteropathy. Fetal Pediatr Pathol 2019;38:534-537.
  • Gorukmez O, Gorukmez O, Havalı C. Novel MECR Mutation in Childhood-Onset dystonia, optic atrophy, and basal ganglia signal abnormalities. Neuropediatrics 2019;50:336-337.
  • Jalkh N, Corbani S, Haidar Z, et al. The added value of WES reanalysis in the field of genetic diagnosis: lessons learned from 200 exomes in the Lebanese population. BMC Med Genomics 2019;12:1-7.
  • Li Q, Sun Y, van IJzendoorn SCD. A Link between Intrahepatic Cholestasis and Genetic Variations in Intracellular Trafficking Regulators. Biology 2021;10:119.
  • Manolio TA, Chisholm RL, Ozenberger B, et al. Implementing genomic medicine in the clinic: the future is here. Genet Med 2013;15:258-267.
  • McNiven V, Gattini D, Siddiqui I, et al. SCYL1 disease and liver transplantation diagnosed by reanalysis of exome sequencing and deletion/duplication analysis of SCYL1. Am J Med Genet A 2021;185:1091-1097
  • Monies D, Abouelhoda M, AlSayed M, et al. The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes. Hum Genet 2017;136:921-939.
  • Nair P, Sabbagh S, Mansour H, et al. Contribution of next generation sequencing in pediatric practice in Lebanon. A study on 213 cases. Mol Genet Genomic Med 2018;6:1041-1052.
  • Ormondroyd E, Mackley MP, Blair E, et al. Insights from early experience of a Rare Disease Genomic Medicine Multidisciplinary Team: a qualitative study. Eur J Hum Genet 2017;25:680-686.
  • Soden SE, Saunders CJ, Willig LK, et al. Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders. Sci Transl Med 2014;6:265ra168.

Genetic variants in rare diseases identified by WES analysis

Yıl 2023, Cilt: 45 Sayı: 1, 22 - 27, 23.01.2023
https://doi.org/10.20515/otd.1115008

Öz

Next-generation sequencing tests have become a part of the diagnostic process in most fields of medicine. Especially with whole-exome sequencing (WES) studies, the rate of diagnosis has increased in rare hereditary diseases. In this study, we aimed to present the results together with the clinical findings of 65 cases whose diseases are suspected to be of genetic origin. Between 2016 and 2019, patients who underwent WES testing in Bursa Yüksek İhtisas Training and Research Hospital Medical Genetics Unit were retrospectively screened and included in the study with their analysis results and clinical findings. In 27 of the 65 cases (41.5 %) included in the study, 30 significant variants were found in relation to their clinical findings. Twenty of these variants (66.7 %) have not been previously reported in literature. Rare diseases encountered in patients within a wide age range, from the fetus to 66 years of age, are presented along with their clinical findings and WES results. Thus, this study contributes to the mutation spectrum of hereditary diseases.

Kaynakça

  • Bhatia NS, Lim JY, Bonnard C, et al. Singapore undiagnosed disease program: genomic analysis AIDS diagnosis and clinical management. SUREKids Working Group. Arch Dis Child 2021;106:31-37.
  • Bowdin S, Ray PN, Cohn RD, Meyn MS. The genome clinic: a multidisciplinary approach to assessing the opportunities and challenges of integrating genomic analysis into clinical care. Hum Mutat 2014;35:513-519.
  • Dixon-Salazar TJ, Silhavy JL, Udpa N, et al. Exome sequencing can improve diagnosis and alter patient management. Sci Transl Med 2012;4:138ra78.
  • Gorukmez O, Gorukmez O, Demiroren K. Novel PLVAP Mutation in Protein Losing Enteropathy. Fetal Pediatr Pathol 2019;38:534-537.
  • Gorukmez O, Gorukmez O, Havalı C. Novel MECR Mutation in Childhood-Onset dystonia, optic atrophy, and basal ganglia signal abnormalities. Neuropediatrics 2019;50:336-337.
  • Jalkh N, Corbani S, Haidar Z, et al. The added value of WES reanalysis in the field of genetic diagnosis: lessons learned from 200 exomes in the Lebanese population. BMC Med Genomics 2019;12:1-7.
  • Li Q, Sun Y, van IJzendoorn SCD. A Link between Intrahepatic Cholestasis and Genetic Variations in Intracellular Trafficking Regulators. Biology 2021;10:119.
  • Manolio TA, Chisholm RL, Ozenberger B, et al. Implementing genomic medicine in the clinic: the future is here. Genet Med 2013;15:258-267.
  • McNiven V, Gattini D, Siddiqui I, et al. SCYL1 disease and liver transplantation diagnosed by reanalysis of exome sequencing and deletion/duplication analysis of SCYL1. Am J Med Genet A 2021;185:1091-1097
  • Monies D, Abouelhoda M, AlSayed M, et al. The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes. Hum Genet 2017;136:921-939.
  • Nair P, Sabbagh S, Mansour H, et al. Contribution of next generation sequencing in pediatric practice in Lebanon. A study on 213 cases. Mol Genet Genomic Med 2018;6:1041-1052.
  • Ormondroyd E, Mackley MP, Blair E, et al. Insights from early experience of a Rare Disease Genomic Medicine Multidisciplinary Team: a qualitative study. Eur J Hum Genet 2017;25:680-686.
  • Soden SE, Saunders CJ, Willig LK, et al. Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders. Sci Transl Med 2014;6:265ra168.
Toplam 13 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm ORİJİNAL MAKALELER / ORIGINAL ARTICLES
Yazarlar

Ozlem Gorukmez 0000-0003-2289-8619

Yayımlanma Tarihi 23 Ocak 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 45 Sayı: 1

Kaynak Göster

Vancouver Gorukmez O. Genetic variants in rare diseases identified by WES analysis. Osmangazi Tıp Dergisi. 2023;45(1):22-7.


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