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Clinical Utility of Molecular Autopsy in Fetal and Pediatric Patients with Suspected Genetic Disorders

Yıl 2022, Cilt 11, Sayı 1, 82 - 89, 19.03.2022
https://doi.org/10.37989/gumussagbil.1078850

Öz

Molecular autopsy is defined as whole exome/genome sequencing (WES/WGS) performed on DNA samples in the postmortem period to clarify the genetic etiology in patients who demised without a diagnosis. With this study, we aim to present our experience with postmortem WES/WGS analysis, in a group of pediatric patients to increase the knowledge on the clinical utility of molecular autopsy and its effect on genetic counseling. A retrospective cohort study was conducted on postmortem WES/WGS analysis records performed between 2017-2021 in Acibadem University Department of Pediatric Genetics. Clinical data and analysis results of patients who died in the perinatal/infancy period without a molecular diagnosis were collected from medical records. A total of 16 cases were included in the study. In 56% of the cases, molecular autopsy revealed a diagnosis. In 10 genes (BBS9, BRAF, SLC12A1, PIEZO1, WDR62, ERCC8, NDUFAF2, RAG1, MOGS, ETFB), 12 variants were detected. Fifty percent of these variants were novel, reported for the first time with this study. Inborn diseases of metabolism (33%) and neurologic disorders (22%) were the most common disease groups. Our results show that WES/WGS analysis yields a high diagnostic rate in the postmortem period. The diagnosis elucidated by molecular autopsy provides invaluable information for the family who has experienced a loss. The identification of the underlying genetic cause enables the family to plan for future pregnancies. Diagnosing a fetus or an infant who was lost without a specific diagnosis helps identify novel genes and further delineate perinatal lethal phenotypes related to known genes.

Kaynakça

  • United Nations Inter-agency Group for Child Mortality Estimation (UN IGME). (2017). “Levels and Trends in Child Mortality: Report 2017”. https://www.un.org/en/development/ desa/population/publications/mortality/child-mortality-report-2017.asp New York: United Nations Children’s Fund.
  • Robson, S.C, Chitty, L.S, Morris, S, Verhoef, T, Ambler, G, Wellesley, D.G, Graham, R, Leader, C, Fisher, J. and Crolla, J.A. (2017). “Evaluation of Array Comparative Genomic Hybridisation in Prenatal Diagnosis Of Fetal Anomalies: A Multicentre Cohort Study With Cost Analysis And Assessment of Patient, Health Professional and Commissioner Preferences for Array Comparative Genomic Hybridisation”. Effic Mech Eval., 4, 1–104.
  • Hillman, S.C, Pretlove, S, Coomarasamy, A, McMullan, D.J, Davison, E.V, Maher, E.R. and Kilby, M.D. (2011). “Additional Information From Array Comparative Genomic Hybridization Technology Over Conventional Karyotyping In Prenatal Diagnosis: A Systematic Review and Meta-Analysis”. Ultrasound Obstet Gynecol., 37, 6–14
  • Yang, Y, Muzny, D.M, Reid, J.G, Bainbridge, M.N, Willis, A, Ward, P.A, Braxton, A, Beuten, J, Xia, F, Niu, Z, Hardison, M, Person, R, Bekheirnia, M.R, Leduc, M.S, Kirby, A, Pham, P, Scull, J, Wang, M, Ding, Y, Plon, S.E, Lupski, J.R, Beaudet, A.L, Gibbs, R.A. and Eng, C.M. (2013). “Clinical Whole-Exome Sequencing for The Diagnosis of Mendelian Disorders”. N Engl J Med., 369 (16), 1502-1511.
  • Lee, H, Deignan, J.L, Dorrani, N, Strom, S.P, Kantarci, S, Quintero-Rivera, F, Das, K, Toy, T, Harry, B, Yourshaw, M, Fox, M, Fogel, B.L, Martinez-Agosto, J.A, Wong, D.A, Chang, V.Y, Shieh, P.B, Palmer, C.G, Dipple, K.M, Grody, W.W, Vilain, E. and Nelson, S.F. (2014). “Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders”. JAMA, 312 (18), 1880-1887.
  • Shamseldin, H.E, Kurdi, W, Almusafri, F, Alnemer, M, Alkaff, A, Babay, Z, Alhashem, A, Tulbah, M, Alsahan, N, Khan, R, Sallout, B, Al Mardawi, E, Seidahmed, M.Z, Meriki, N, Alsaber, Y, Qari, A, Khalifa, O, Eyaid, W, Rahbeeni, Z, Kurdi, A, Hashem, M, Alshidi, T, Al-Obeid, E, Abdulwahab, F, Ibrahim, N, Ewida, N, El-Akouri, K, Al Mulla, M, Ben-Omran, T, Pergande, M, Cirak, S, Al Tala, S, Shaheen, R, Faqeih E. and Alkuraya F.S. (2018). “Molecular Autopsy in Maternal-Fetal Medicine”. Genet Med., 20 (4), 420-427.
  • Quinlan-Jones, E, Lord, J, Williams, D, Hamilton, S, Marton, T, Eberhardt, R.Y, Rinck, G, Prigmore, E, Keelagher, R, McMullan, D.J, Maher, E.R, Hurles, M.E. and Kilby M.D. (2019). “Molecular Autopsy by Trio Exome Sequencing (ES) and Postmortem Examination in Fetuses and Neonates with Prenatally Identified Structural Anomalies”. Genet Med., 21 (5), 1065-1073.
  • Nykamp, K, Anderson, M, Powers, M, Garcia, J, Herrera, B, Ho, Y.Y, Kobayashi, Y, Patil, N, Thusberg, J, Westbrook, M, Invitae Clinical Genomics Group. and Topper S. (2017). “Sherloc: A Comprehensive Refinement of The ACMG-AMP Variant Classification Criteria”. Genet Med., 19 (10), 1105-1117.
  • Colombo, I, Finocchiaro, G, Garavaglia, B, Garbuglio, N, Yamaguchi, S, Frerman, F.E, Berra, B. and DiDonato, S. (1994). “Mutations And Polymorphisms of The Gene Encoding the Beta-Subunit of The Electron Transfer Flavoprotein in Three Patients with Glutaric Acidemia Type II”. Hum Mol Genet., 3 (3), 429-35. doi: 10.1093/hmg/3.3.429.
  • De Praeter, C.M, Gerwig, G.J, Bause, E, Nuytinck, L.K, Vliegenthart, J.F, Breuer, W, Kamerling, J.P, Espeel, M.F, Martin, J.J, De Paepe, A.M, Chan, N.W, Dacremont G.A. and Van Coster R.N. (2000). “A Novel Disorder Caused by Defective Biosynthesis of N-Linked Oligosaccharides Due to Glucosidase I Deficiency”. Am J Hum Genet., 66 (6), 1744-56. doi: 10.1086/302948.
  • Yang, Y, Muzny, D.M, Xia, F, Niu, Z, Person, R, Ding, Y, Ward, P, Braxton, A, Wang, M, Buhay, C, Veeraraghavan, N, Hawes, A, Chiang, T, Leduc, M, Beuten, J, Zhang, J, He, W, Scull, J, Willis, A, Landsverk, M,
  • Craigen, W.J, Bekheirnia, M.R, Stray-Pedersen, A, Liu, P, Wen, S, Alcaraz, W, Cui, H, Walkiewicz, M, Reid, J, Bainbridge, M, Patel, A, Boerwinkle, E, Beaudet, A.L, Lupski, J.R, Plon, S.E, Gibbs, R.A. and Eng, C.M. (2014). “Molecular Findings Among Patients Referred for Clinical Whole-Exome Sequencing”. JAMA. 312 (18), 1870-1879.
  • Nasr, M, Makki, S, Alfaifi, A, Akleh, H, Yamani, S, Bubshait, D, Mahnashi, M, Basha, T, Alsagheir, A, Abu Khaled, M, Alsaleem, K, Almugbel, M, Badawi, M, Bashiri, F, Bohlega, S, Sulaiman, R, Tous, E,
  • Ahmed, S, Algoufi, T, Al-Mousa, H, Alaki, E, Alhumaidi, S, Alghamdi, H, Alghamdi, M, Sahly, A, Nahrir, S, Al-Ahmari, A, Alkuraya, H, Almehaidib, A, Abanemai, M, Alsohaibaini, F, Alsaud, B, Arnaout, R, Abdel-Salam, G.M.H, Aldhekri, H, Alkhater, S, Alqadi, K, Alsabban, E, Alshareef, T, Awartani, K, Banjar, H, Alsahan, N, Abosoudah, I,
  • Alashwal, A, Aldekhail, W, Alhajjar, S, Al-Mayouf, S, Alsemari, A, Alshuaibi, W, Altala, S, Altalhi, A, Baz, S, Hamad, M, Abalkhail, T, Alenazi, B, Alkaff, A, Almohareb, F, Al Mutairi, F, Alsaleh, M, Alsonbul, A, Alzelaye, S, Bahzad, S, Manee, A.B, Jarrad, O, Meriki, N, Albeirouti,
  • B, Alqasmi, A, AlBalwi, M, Makhseed, N, Hassan, S, Salih, I, Salih, M.A, Shaheen, M, Sermin, S, Shahrukh, S, Hashmi, S, Shawli, A, Tajuddin, A, Tamim, A, Alnahari, A, Ghemlas, I, Hussein, M, Wali, S, Murad, H, Meyer B.F. and Alkuraya F.S. (2019). ‘’Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing In A Highly Consanguineous Population’’. Am J Hum Genet., 104 (6), 1182-1201.
  • Alghamdi, A.M, Alrasheedi, A, Alghamdi, E, Adly N, AlAali, W.Y, Alhashem, A, Alshahrani, A, Shamseldin, H, Alkuraya, F.S. and Alfadhel M. (2021). “Molecular Autopsy By Proxy In Preconception Counseling”. Clin Genet. 100 (6), 678-691. doi: 10.1111/cge.14049.
  • Yates, C.L, Monaghan, K.G, Copenheaver, D, Retterer, K, Scuffins, J, Kucera, C.R, Friedman, B, Richard, G. and Juusola, J. (2017). “Whole-Exome Sequencing On Deceased Fetuses With Ultrasound Anomalies: Expanding Our Knowledge Of Genetic Disease During Fetal Development”. Genet Med. 19, 1171–1178.
  • Aarabi, M, Sniezek, O, Jiang, H, Saller, D.N, Bellissimo, D, Yatsenko, S.A. and Rajkovic, A. (2018). “Importance Of Complete Phenotyping In Prenatal Whole Exome Sequencing”. Hum Genet. 137, 175–181.

Genetik Hastalık Şüphesi Olan Fetal ve Pediatrik Hastalarda Moleküler Otopsinin Klinik Faydası

Yıl 2022, Cilt 11, Sayı 1, 82 - 89, 19.03.2022
https://doi.org/10.37989/gumussagbil.1078850

Öz

Moleküler otopsi, herhangi bir tanı konulamadan kaybedilen hastalarda genetik etiyolojiyi aydınlatmak üzere postmortem dönemde gerçekleştirilen tüm ekzom/genom dizilemeyi (WES/WGS) kapsamaktadır. Çalışmamızın amacı pediatrik yaş grubunda postmortem WES/WGS tecrübemizi paylaşarak, moleküler otopsinin klinik kullanımdaki yararını ve genetik danışmanlık üzerindeki etkisini sunmaktır. Çalışmamız retrospektif kohort çalışması olarak planlandı. Acıbadem Üniversitesi Pediatrik Genetik Anabilim Dalı'nda 2017-2021 yılları arasında, perinatal veya infant döneminde moleküler tanı konulamadan kaybedilen ve postmortem WES/WGS yapılan hastaların klinik verileri ve moleküler sonuçları hastalara ait tıbbi kayıtlar incelenerek toplandı. Çalışmaya toplam 16 vaka dahil edildi. Vakaların %56'sında moleküler otopsi sonrası tanı konuldu. On gende (BBS9, BRAF, SLC12A1, PIEZO1, WDR62, ERCC8, NDUFAF2, RAG1, MOGS, ETFB), toplam 12 varyant tespit edildi. Bu varyantların %50'si daha önce bildirilmeyen, novel varyantlardı. Doğuştan metabolizma hastalıkları (%33) ve nörolojik bozukluklar (%22) en sık görülen hastalık grupları olarak öne çıktı. Sonuçlarımız, WES/WGS analizinin özellikle ülkemiz gibi akraba evliliği oranının yüksek olduğu bölgelerde ölüm sonrası dönemde yüksek bir tanı oranına sahip olduğunu göstermektedir. Moleküler otopsi ile aydınlatılan tanı, kayıp yaşayan aile için gelecekteki gebeliklerin planlanması ve yönetimi açısından çok değerli bilgiler sağlamaktadır. Ayrıca, spesifik bir tanı olmadan kaybedilen fetüs veya infantların teşhisi, yeni genlerin tanımlanmasına ve bilinen genlerle ilgili perinatal ölümcül fenotiplerin belirlenmesine de olanak tanımaktadır.

Kaynakça

  • United Nations Inter-agency Group for Child Mortality Estimation (UN IGME). (2017). “Levels and Trends in Child Mortality: Report 2017”. https://www.un.org/en/development/ desa/population/publications/mortality/child-mortality-report-2017.asp New York: United Nations Children’s Fund.
  • Robson, S.C, Chitty, L.S, Morris, S, Verhoef, T, Ambler, G, Wellesley, D.G, Graham, R, Leader, C, Fisher, J. and Crolla, J.A. (2017). “Evaluation of Array Comparative Genomic Hybridisation in Prenatal Diagnosis Of Fetal Anomalies: A Multicentre Cohort Study With Cost Analysis And Assessment of Patient, Health Professional and Commissioner Preferences for Array Comparative Genomic Hybridisation”. Effic Mech Eval., 4, 1–104.
  • Hillman, S.C, Pretlove, S, Coomarasamy, A, McMullan, D.J, Davison, E.V, Maher, E.R. and Kilby, M.D. (2011). “Additional Information From Array Comparative Genomic Hybridization Technology Over Conventional Karyotyping In Prenatal Diagnosis: A Systematic Review and Meta-Analysis”. Ultrasound Obstet Gynecol., 37, 6–14
  • Yang, Y, Muzny, D.M, Reid, J.G, Bainbridge, M.N, Willis, A, Ward, P.A, Braxton, A, Beuten, J, Xia, F, Niu, Z, Hardison, M, Person, R, Bekheirnia, M.R, Leduc, M.S, Kirby, A, Pham, P, Scull, J, Wang, M, Ding, Y, Plon, S.E, Lupski, J.R, Beaudet, A.L, Gibbs, R.A. and Eng, C.M. (2013). “Clinical Whole-Exome Sequencing for The Diagnosis of Mendelian Disorders”. N Engl J Med., 369 (16), 1502-1511.
  • Lee, H, Deignan, J.L, Dorrani, N, Strom, S.P, Kantarci, S, Quintero-Rivera, F, Das, K, Toy, T, Harry, B, Yourshaw, M, Fox, M, Fogel, B.L, Martinez-Agosto, J.A, Wong, D.A, Chang, V.Y, Shieh, P.B, Palmer, C.G, Dipple, K.M, Grody, W.W, Vilain, E. and Nelson, S.F. (2014). “Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders”. JAMA, 312 (18), 1880-1887.
  • Shamseldin, H.E, Kurdi, W, Almusafri, F, Alnemer, M, Alkaff, A, Babay, Z, Alhashem, A, Tulbah, M, Alsahan, N, Khan, R, Sallout, B, Al Mardawi, E, Seidahmed, M.Z, Meriki, N, Alsaber, Y, Qari, A, Khalifa, O, Eyaid, W, Rahbeeni, Z, Kurdi, A, Hashem, M, Alshidi, T, Al-Obeid, E, Abdulwahab, F, Ibrahim, N, Ewida, N, El-Akouri, K, Al Mulla, M, Ben-Omran, T, Pergande, M, Cirak, S, Al Tala, S, Shaheen, R, Faqeih E. and Alkuraya F.S. (2018). “Molecular Autopsy in Maternal-Fetal Medicine”. Genet Med., 20 (4), 420-427.
  • Quinlan-Jones, E, Lord, J, Williams, D, Hamilton, S, Marton, T, Eberhardt, R.Y, Rinck, G, Prigmore, E, Keelagher, R, McMullan, D.J, Maher, E.R, Hurles, M.E. and Kilby M.D. (2019). “Molecular Autopsy by Trio Exome Sequencing (ES) and Postmortem Examination in Fetuses and Neonates with Prenatally Identified Structural Anomalies”. Genet Med., 21 (5), 1065-1073.
  • Nykamp, K, Anderson, M, Powers, M, Garcia, J, Herrera, B, Ho, Y.Y, Kobayashi, Y, Patil, N, Thusberg, J, Westbrook, M, Invitae Clinical Genomics Group. and Topper S. (2017). “Sherloc: A Comprehensive Refinement of The ACMG-AMP Variant Classification Criteria”. Genet Med., 19 (10), 1105-1117.
  • Colombo, I, Finocchiaro, G, Garavaglia, B, Garbuglio, N, Yamaguchi, S, Frerman, F.E, Berra, B. and DiDonato, S. (1994). “Mutations And Polymorphisms of The Gene Encoding the Beta-Subunit of The Electron Transfer Flavoprotein in Three Patients with Glutaric Acidemia Type II”. Hum Mol Genet., 3 (3), 429-35. doi: 10.1093/hmg/3.3.429.
  • De Praeter, C.M, Gerwig, G.J, Bause, E, Nuytinck, L.K, Vliegenthart, J.F, Breuer, W, Kamerling, J.P, Espeel, M.F, Martin, J.J, De Paepe, A.M, Chan, N.W, Dacremont G.A. and Van Coster R.N. (2000). “A Novel Disorder Caused by Defective Biosynthesis of N-Linked Oligosaccharides Due to Glucosidase I Deficiency”. Am J Hum Genet., 66 (6), 1744-56. doi: 10.1086/302948.
  • Yang, Y, Muzny, D.M, Xia, F, Niu, Z, Person, R, Ding, Y, Ward, P, Braxton, A, Wang, M, Buhay, C, Veeraraghavan, N, Hawes, A, Chiang, T, Leduc, M, Beuten, J, Zhang, J, He, W, Scull, J, Willis, A, Landsverk, M,
  • Craigen, W.J, Bekheirnia, M.R, Stray-Pedersen, A, Liu, P, Wen, S, Alcaraz, W, Cui, H, Walkiewicz, M, Reid, J, Bainbridge, M, Patel, A, Boerwinkle, E, Beaudet, A.L, Lupski, J.R, Plon, S.E, Gibbs, R.A. and Eng, C.M. (2014). “Molecular Findings Among Patients Referred for Clinical Whole-Exome Sequencing”. JAMA. 312 (18), 1870-1879.
  • Nasr, M, Makki, S, Alfaifi, A, Akleh, H, Yamani, S, Bubshait, D, Mahnashi, M, Basha, T, Alsagheir, A, Abu Khaled, M, Alsaleem, K, Almugbel, M, Badawi, M, Bashiri, F, Bohlega, S, Sulaiman, R, Tous, E,
  • Ahmed, S, Algoufi, T, Al-Mousa, H, Alaki, E, Alhumaidi, S, Alghamdi, H, Alghamdi, M, Sahly, A, Nahrir, S, Al-Ahmari, A, Alkuraya, H, Almehaidib, A, Abanemai, M, Alsohaibaini, F, Alsaud, B, Arnaout, R, Abdel-Salam, G.M.H, Aldhekri, H, Alkhater, S, Alqadi, K, Alsabban, E, Alshareef, T, Awartani, K, Banjar, H, Alsahan, N, Abosoudah, I,
  • Alashwal, A, Aldekhail, W, Alhajjar, S, Al-Mayouf, S, Alsemari, A, Alshuaibi, W, Altala, S, Altalhi, A, Baz, S, Hamad, M, Abalkhail, T, Alenazi, B, Alkaff, A, Almohareb, F, Al Mutairi, F, Alsaleh, M, Alsonbul, A, Alzelaye, S, Bahzad, S, Manee, A.B, Jarrad, O, Meriki, N, Albeirouti,
  • B, Alqasmi, A, AlBalwi, M, Makhseed, N, Hassan, S, Salih, I, Salih, M.A, Shaheen, M, Sermin, S, Shahrukh, S, Hashmi, S, Shawli, A, Tajuddin, A, Tamim, A, Alnahari, A, Ghemlas, I, Hussein, M, Wali, S, Murad, H, Meyer B.F. and Alkuraya F.S. (2019). ‘’Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing In A Highly Consanguineous Population’’. Am J Hum Genet., 104 (6), 1182-1201.
  • Alghamdi, A.M, Alrasheedi, A, Alghamdi, E, Adly N, AlAali, W.Y, Alhashem, A, Alshahrani, A, Shamseldin, H, Alkuraya, F.S. and Alfadhel M. (2021). “Molecular Autopsy By Proxy In Preconception Counseling”. Clin Genet. 100 (6), 678-691. doi: 10.1111/cge.14049.
  • Yates, C.L, Monaghan, K.G, Copenheaver, D, Retterer, K, Scuffins, J, Kucera, C.R, Friedman, B, Richard, G. and Juusola, J. (2017). “Whole-Exome Sequencing On Deceased Fetuses With Ultrasound Anomalies: Expanding Our Knowledge Of Genetic Disease During Fetal Development”. Genet Med. 19, 1171–1178.
  • Aarabi, M, Sniezek, O, Jiang, H, Saller, D.N, Bellissimo, D, Yatsenko, S.A. and Rajkovic, A. (2018). “Importance Of Complete Phenotyping In Prenatal Whole Exome Sequencing”. Hum Genet. 137, 175–181.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Bilimleri ve Hizmetleri
Bölüm Araştırma Makaleleri
Yazarlar

Ozlem AKGUN-DOGAN
ACIBADEM ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0002-8310-4053
Türkiye


Nihat Buğra AĞAOĞLU (Sorumlu Yazar)
SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL ÜMRANİYE SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ
0000-0002-9336-0552
Türkiye


Yasemin ALANAY
ACIBADEM ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0003-0683-9731
Türkiye

Yayımlanma Tarihi 19 Mart 2022
Yayınlandığı Sayı Yıl 2022, Cilt 11, Sayı 1

Kaynak Göster

Bibtex @araştırma makalesi { gumussagbil1078850, journal = {Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi}, eissn = {2146-9954}, address = {}, publisher = {Gümüşhane Üniversitesi}, year = {2022}, volume = {11}, number = {1}, pages = {82 - 89}, doi = {10.37989/gumussagbil.1078850}, title = {Clinical Utility of Molecular Autopsy in Fetal and Pediatric Patients with Suspected Genetic Disorders}, key = {cite}, author = {Akgun-dogan, Ozlem and Ağaoğlu, Nihat Buğra and Alanay, Yasemin} }
APA Akgun-dogan, O. , Ağaoğlu, N. B. & Alanay, Y. (2022). Clinical Utility of Molecular Autopsy in Fetal and Pediatric Patients with Suspected Genetic Disorders . Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi , 11 (1) , 82-89 . DOI: 10.37989/gumussagbil.1078850
MLA Akgun-dogan, O. , Ağaoğlu, N. B. , Alanay, Y. "Clinical Utility of Molecular Autopsy in Fetal and Pediatric Patients with Suspected Genetic Disorders" . Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 11 (2022 ): 82-89 <https://dergipark.org.tr/tr/pub/gumussagbil/issue/68960/1078850>
Chicago Akgun-dogan, O. , Ağaoğlu, N. B. , Alanay, Y. "Clinical Utility of Molecular Autopsy in Fetal and Pediatric Patients with Suspected Genetic Disorders". Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 11 (2022 ): 82-89
RIS TY - JOUR T1 - Clinical Utility of Molecular Autopsy in Fetal and Pediatric Patients with Suspected Genetic Disorders AU - Ozlem Akgun-dogan , Nihat Buğra Ağaoğlu , Yasemin Alanay Y1 - 2022 PY - 2022 N1 - doi: 10.37989/gumussagbil.1078850 DO - 10.37989/gumussagbil.1078850 T2 - Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi JF - Journal JO - JOR SP - 82 EP - 89 VL - 11 IS - 1 SN - -2146-9954 M3 - doi: 10.37989/gumussagbil.1078850 UR - https://doi.org/10.37989/gumussagbil.1078850 Y2 - 2022 ER -
EndNote %0 Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi Clinical Utility of Molecular Autopsy in Fetal and Pediatric Patients with Suspected Genetic Disorders %A Ozlem Akgun-dogan , Nihat Buğra Ağaoğlu , Yasemin Alanay %T Clinical Utility of Molecular Autopsy in Fetal and Pediatric Patients with Suspected Genetic Disorders %D 2022 %J Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi %P -2146-9954 %V 11 %N 1 %R doi: 10.37989/gumussagbil.1078850 %U 10.37989/gumussagbil.1078850
ISNAD Akgun-dogan, Ozlem , Ağaoğlu, Nihat Buğra , Alanay, Yasemin . "Clinical Utility of Molecular Autopsy in Fetal and Pediatric Patients with Suspected Genetic Disorders". Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 11 / 1 (Mart 2022): 82-89 . https://doi.org/10.37989/gumussagbil.1078850
AMA Akgun-dogan O. , Ağaoğlu N. B. , Alanay Y. Clinical Utility of Molecular Autopsy in Fetal and Pediatric Patients with Suspected Genetic Disorders. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. 2022; 11(1): 82-89.
Vancouver Akgun-dogan O. , Ağaoğlu N. B. , Alanay Y. Clinical Utility of Molecular Autopsy in Fetal and Pediatric Patients with Suspected Genetic Disorders. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. 2022; 11(1): 82-89.
IEEE O. Akgun-dogan , N. B. Ağaoğlu ve Y. Alanay , "Clinical Utility of Molecular Autopsy in Fetal and Pediatric Patients with Suspected Genetic Disorders", Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, c. 11, sayı. 1, ss. 82-89, Mar. 2022, doi:10.37989/gumussagbil.1078850