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CLINICAL AND MOLECULAR RESULTS OF SIX CASES WITH ROBERTS SYNDROME: REVIEW OF CASES FROM TURKIYE

Yıl 2022, Cilt: 85 Sayı: 4, 501 - 509, 28.10.2022

Öz

Objective: Roberts syndrome is a rare autosomal recessive disease characterized by limb defects, prenatal onset growth retardation, and craniofacial anomalies. We aimed to compare the clinical and molecular findings of six cases with Roberts syndrome with the previously reported patients from Turkiye and to emphasize that the definitive diagnosis can be made in the intrauterine period with cytogenetic tests in the early period without the need to wait for molecular test results.
Materials and Methods: Six cases, diagnosed with Roberts syndrome, in our outpatient clinic of Istanbul University, Istanbul Medical Faculty, Medical Genetics Department between 2015-2021 were included in the study. The family history, clinical information, and cytogenetic and molecular findings of the patients were retrospectively reviewed and compared with cases reported from Turkiye in the literature. G and C-banding techniques and Sanger sequencing of the ESCO2 gene were performed.
Results:Pathogenic variants in homozygous in four and compound heterozygous in two patients in the ESCO2 gene were identified. Compound heterozygous c.[417dup];[1131+1G>A] (p.[(Pro140Thrfs*8)];[(?)]) in case 1, and c.[1111dup];[760del] (p.[(Thr371Asnfs*32)];[(Thr254Leufs*13)]) in case 6, homozygous c.1131+1G>A (p.(?)) in case 2, case 3 and case 5, and homozygous c.1111dup (p.(Thr371Asnfs*32)) mutations in case 4 were detected. The variants reported in our case series were previously associated with the disease. The first demonstration of the c.760del mutation in a Turkish case contributed to the mutation profile in our population that caused this disease. Although all previously reported Turkish patients were homozygous, we have detected two patients with compound heterozygous mutations indicating that the disease should also be considered in families with no consanguinity.

Kaynakça

  • 1. Vega H, Waisfisz Q, Gordillo M, Sakai N, Yanagihara I, Yamada M, et al. Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion. Nat Genet 2005;37(5):468-70. [CrossRef] google scholar
  • 2. Roberts JB. A child with double cleft of lip and palate, protrusion of the intermaxillary portion of the upper jaw and imperfect development of the bones of the four extremities. Ann Surg 1919;70:252-3. google scholar
  • 3. Herrmann J, Feingold M, Tuffli GA, Opitz JM. A familial dysmorphogenetic syndrome of limb deformities, characteristic facial appearance and associated anomalies: the ‘pseudothalidomide’ or ‘SC-syndrome’. Birth Defects Orig Art Ser 1969;5:81-9. google scholar
  • 4. Van Den Berg DJ, Francke U. Roberts syndrome: A review of 100 cases and a new rating system for severity. Am J Med Genet 1993;47:1104-23. [CrossRef] google scholar
  • 5. Gordillo M, Vega H, Trainer AH, Hou F, Sakai N, Luque R, et al. The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity. Hum Mol Genet 2008;17(14):2172-80. [CrossRef] google scholar
  • 6. Tomkins D, Hunter A, Roberts M. Cytogenetic findings in Roberts-SC phocomelia syndrome(s). Am J Med Genet 1979;4:17-26. [CrossRef] google scholar
  • 7. Benn PA, Tantravahi U. Chromosome staining and banding techniques. In: Rooney DE, editor. Human Cytogenetics: Constitutional analysis, 3rd ed. Oxford, UK: Oxford University Press; 2001.p.99-128. google scholar
  • 8. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17(5):405-24. [CrossRef] google scholar
  • 9. Vega H, Gordillo M, Jabs EW. ESCO2 and Roberts syndrome. In: Erickson RP, Wynshaw-Boris AJ, editors. Epstein’s Inborn Errors of Development: The Molecular Basis of Clinical Disorders of Morphogenesis. 3rd ed. Oxford, UK: Oxford University Press; 2016.p.1005-9. [CrossRef] google scholar
  • 10. Vega H, Trainer AH, Gordillo M, Crosier M, Kayserili H, Skovby F, et al. Phenotypic variability in 49 cases of ESCO2 mutations, including novel missense and codon deletion in the acetyltransferase domain, correlates with ESCO2 expression and establishes the clinical criteria for Roberts syndrome. J Med Genet 2010;47(1):30. [CrossRef] google scholar
  • 11. Goh ES, Li C, Horsburgh S, Kasai Y, Kolomietz E, Morel CF. The Roberts syndrome/SC phocomelia spectrum a case report of an adult with review of the literature. Am J Med Genet A 2010;152A(2):472-8. [CrossRef] google scholar
  • 12. Kantaputra PN, Dejkhamron P, Intachai W, Ngamphiw C, Kawasaki K, Ohazama A, et al. Juberg-Hayward syndrome is a cohesinopathy, caused by mutation in ESCO2. Eur J Orthod 2021;43(1):45-50. [CrossRef] google scholar
  • 13. Schneeberger PE, Nayak SS, Fuchs S, Kutsche K, Girisha KM. Roberts syndrome in an Indian patient with humeroradial synostosis, congenital elbow contractures and a novel homozygous splice variant in ESCO2. Am J Med Genet A 2020;182(11):2793-6. [CrossRef] google scholar
  • 14. Mengen E, Kotan LD, Ucakturk SA, Topaloglu AK, Yuksel B. A novel frameshift mutation in ESCO2 gene in Roberts syndrome. J Coll Physicians Surg Pak 2018;28(5):403-5. [CrossRef] google scholar
  • 15. Avci S, Toksoy G, Bagirova G, Altunoglu U, Karaman B, Kayserili H, et al. Clinical classification of radial ray defects and research into etiopathogenesis. J Ist Faculty Med 2018;81(4):127-38. [CrossRef] google scholar
  • 16. Sezer A, Kayhan G, Zenker M, Percin EF. Hypopigmented patches in Roberts/SC phocomelia syndrome occur via aneuploidy susceptibility. Eur J Med Genet 2019;62(12):103608. [CrossRef] google scholar
  • 17. Dogan M, Firinci F, Balci YI, Zeybek S, Ozgürler F, Erdogan I, et al. The Roberts syndrome: a case report of an infant with valvular aortic stenosis and mutation in ESCO2. J Pak Med Assoc 2014;64(4):457-60. google scholar
  • 18. Colombo EA, Mutlu-Albayrak H, Shafeghati Y, Balasar M, Piard J, Gentilini D, et al. Phenotypic overlap of Roberts and Baller-Gerold syndromes in two patients with craniosynostosis, limb reductions, and ESCO2 mutations. Front Pediatr 2019;7:210. [CrossRef] google scholar
  • 19. Schüle B, Oviedo A, Johnston K, Pai S, Francke U. Inactivating mutations in ESCO2 cause SC phocomelia and Roberts syndrome: no phenotype-genotype correlation. Am J Hum Genet 2005;77(6):1117-28. [CrossRef] google scholar

ROBERTS SENDROMLU ALTI OLGUNUN KLİNİK VE MOLEKÜLER SONUÇLARI İLE TÜRKİYE'DEN BİLDİRİLEN OLGULARIN GÖZDEN GEÇİRİLMESİ

Yıl 2022, Cilt: 85 Sayı: 4, 501 - 509, 28.10.2022

Öz

Amaç: Roberts sendromu; ekstremite anomalileri, prenatal başlangıçlı büyüme gelişme geriliği ve kraniyofasiyal anomaliler ile karakterize nadir görülen otozomal resesif kalıtılan bir hastalıktır. Roberts sendromlu altı olgunun klinik ve moleküler bulgularını Türkiye'den daha önce bildirilen olgularla karşılaştırmayı ve moleküler test sonuçlarını beklemeye gerek kalmadan erken dönemde sitogenetik testlerle kesin tanının intrauterin dönemde yapılabileceğini vurgulamayı amaçladık.
Gereç ve Yöntem: 2015-2021 yılları arasında İstanbul Üniversitesi İstanbul Tıp Fakültesi Tıbbi Genetik Anabilim Dalı polikliniğimizde Roberts sendromu tanısı alan altı olgu çalışmaya dahil edildi. Hastaların aile öyküsü, klinik bilgileri, sitogenetik ve moleküler bulguları retrospektif olarak incelendi ve literatürde Türkiye'den bildirilen olgularla karşılaştırıldı. G ve C-bantlama teknikleri ve ESCO2 geninin Sanger dizilimi gerçekleştirildi.
Bulgular:ESCO2 geninde dört olguda homozigot ve iki olguda bileşik heterozigot patojenik varyantlar tespit edildi. Olgu 1’de birleşik heterozigot c.[417dup];[1131+1G>A] (p.[(Pro140Thrfs*8)];[(?)]) ve olgu 6’da c.[1111dup];[760del](p.[(Thr371Asnfs*32)]; [(Thr254Leufs*13)]) ile olgu 2, olgu 3 ve olgu 5’te homozigot c.1131+1G>A (p.(?)), olgu 4’te homozigot c.1111dup (p.(Thr371Asnfs*32)) mutasyonları saptandı. Olgu serimizde bildirilen patolojik varyantlar daha önce hastalıkla ilişkilendirilmiştir. c.760del mutasyonunun ilk kez Türk bir olguda gösterilmesi bu hastalığa neden olan toplumuzdaki mutasyon profiline katkısı olmuştur. Ayrıca literatürde daha önce yayınlanan Türk olgularda homozigot mutasyon saptanmasına rağmen bizim olgu serimizde ebeveynleri arasında akrabalık ilişkisi olmayan iki olguda birleşik heterozigot mutasyonun gösterilmesi bu sendromun akrabalık ilişkisi olmayan vakalarda da rastlanılacağını göstermektedir.

Kaynakça

  • 1. Vega H, Waisfisz Q, Gordillo M, Sakai N, Yanagihara I, Yamada M, et al. Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion. Nat Genet 2005;37(5):468-70. [CrossRef] google scholar
  • 2. Roberts JB. A child with double cleft of lip and palate, protrusion of the intermaxillary portion of the upper jaw and imperfect development of the bones of the four extremities. Ann Surg 1919;70:252-3. google scholar
  • 3. Herrmann J, Feingold M, Tuffli GA, Opitz JM. A familial dysmorphogenetic syndrome of limb deformities, characteristic facial appearance and associated anomalies: the ‘pseudothalidomide’ or ‘SC-syndrome’. Birth Defects Orig Art Ser 1969;5:81-9. google scholar
  • 4. Van Den Berg DJ, Francke U. Roberts syndrome: A review of 100 cases and a new rating system for severity. Am J Med Genet 1993;47:1104-23. [CrossRef] google scholar
  • 5. Gordillo M, Vega H, Trainer AH, Hou F, Sakai N, Luque R, et al. The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity. Hum Mol Genet 2008;17(14):2172-80. [CrossRef] google scholar
  • 6. Tomkins D, Hunter A, Roberts M. Cytogenetic findings in Roberts-SC phocomelia syndrome(s). Am J Med Genet 1979;4:17-26. [CrossRef] google scholar
  • 7. Benn PA, Tantravahi U. Chromosome staining and banding techniques. In: Rooney DE, editor. Human Cytogenetics: Constitutional analysis, 3rd ed. Oxford, UK: Oxford University Press; 2001.p.99-128. google scholar
  • 8. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17(5):405-24. [CrossRef] google scholar
  • 9. Vega H, Gordillo M, Jabs EW. ESCO2 and Roberts syndrome. In: Erickson RP, Wynshaw-Boris AJ, editors. Epstein’s Inborn Errors of Development: The Molecular Basis of Clinical Disorders of Morphogenesis. 3rd ed. Oxford, UK: Oxford University Press; 2016.p.1005-9. [CrossRef] google scholar
  • 10. Vega H, Trainer AH, Gordillo M, Crosier M, Kayserili H, Skovby F, et al. Phenotypic variability in 49 cases of ESCO2 mutations, including novel missense and codon deletion in the acetyltransferase domain, correlates with ESCO2 expression and establishes the clinical criteria for Roberts syndrome. J Med Genet 2010;47(1):30. [CrossRef] google scholar
  • 11. Goh ES, Li C, Horsburgh S, Kasai Y, Kolomietz E, Morel CF. The Roberts syndrome/SC phocomelia spectrum a case report of an adult with review of the literature. Am J Med Genet A 2010;152A(2):472-8. [CrossRef] google scholar
  • 12. Kantaputra PN, Dejkhamron P, Intachai W, Ngamphiw C, Kawasaki K, Ohazama A, et al. Juberg-Hayward syndrome is a cohesinopathy, caused by mutation in ESCO2. Eur J Orthod 2021;43(1):45-50. [CrossRef] google scholar
  • 13. Schneeberger PE, Nayak SS, Fuchs S, Kutsche K, Girisha KM. Roberts syndrome in an Indian patient with humeroradial synostosis, congenital elbow contractures and a novel homozygous splice variant in ESCO2. Am J Med Genet A 2020;182(11):2793-6. [CrossRef] google scholar
  • 14. Mengen E, Kotan LD, Ucakturk SA, Topaloglu AK, Yuksel B. A novel frameshift mutation in ESCO2 gene in Roberts syndrome. J Coll Physicians Surg Pak 2018;28(5):403-5. [CrossRef] google scholar
  • 15. Avci S, Toksoy G, Bagirova G, Altunoglu U, Karaman B, Kayserili H, et al. Clinical classification of radial ray defects and research into etiopathogenesis. J Ist Faculty Med 2018;81(4):127-38. [CrossRef] google scholar
  • 16. Sezer A, Kayhan G, Zenker M, Percin EF. Hypopigmented patches in Roberts/SC phocomelia syndrome occur via aneuploidy susceptibility. Eur J Med Genet 2019;62(12):103608. [CrossRef] google scholar
  • 17. Dogan M, Firinci F, Balci YI, Zeybek S, Ozgürler F, Erdogan I, et al. The Roberts syndrome: a case report of an infant with valvular aortic stenosis and mutation in ESCO2. J Pak Med Assoc 2014;64(4):457-60. google scholar
  • 18. Colombo EA, Mutlu-Albayrak H, Shafeghati Y, Balasar M, Piard J, Gentilini D, et al. Phenotypic overlap of Roberts and Baller-Gerold syndromes in two patients with craniosynostosis, limb reductions, and ESCO2 mutations. Front Pediatr 2019;7:210. [CrossRef] google scholar
  • 19. Schüle B, Oviedo A, Johnston K, Pai S, Francke U. Inactivating mutations in ESCO2 cause SC phocomelia and Roberts syndrome: no phenotype-genotype correlation. Am J Hum Genet 2005;77(6):1117-28. [CrossRef] google scholar
Toplam 19 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm ARAŞTIRMA
Yazarlar

Ayça Dilruba Aslanger 0000-0003-1770-1762

Tugba Kalayci Bu kişi benim 0000-0002-9963-5916

Esma Nur Konur Bu kişi benim 0000-0002-5074-8071

Çağrı Güleç 0000-0002-1256-9574

Şahin Avcı 0000-0001-9545-6657

Umut Altunoğlu 0000-0002-3172-5368

Volkan Karaman 0000-0001-8777-3548

Güven Toksoy 0000-0002-8103-9980

Birsen Karaman 0000-0001-8640-0176

Seher Başaran 0000-0001-8668-4746

Oya Uyguner 0000-0002-2035-4338

Gözde Yeşil Sayın 0000-0003-1964-6306

Yayımlanma Tarihi 28 Ekim 2022
Gönderilme Tarihi 20 Temmuz 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 85 Sayı: 4

Kaynak Göster

APA Aslanger, A. D., Kalayci, T., Konur, E. N., Güleç, Ç., vd. (2022). CLINICAL AND MOLECULAR RESULTS OF SIX CASES WITH ROBERTS SYNDROME: REVIEW OF CASES FROM TURKIYE. Journal of Istanbul Faculty of Medicine, 85(4), 501-509.
AMA Aslanger AD, Kalayci T, Konur EN, Güleç Ç, Avcı Ş, Altunoğlu U, Karaman V, Toksoy G, Karaman B, Başaran S, Uyguner O, Yeşil Sayın G. CLINICAL AND MOLECULAR RESULTS OF SIX CASES WITH ROBERTS SYNDROME: REVIEW OF CASES FROM TURKIYE. İst Tıp Fak Derg. Ekim 2022;85(4):501-509.
Chicago Aslanger, Ayça Dilruba, Tugba Kalayci, Esma Nur Konur, Çağrı Güleç, Şahin Avcı, Umut Altunoğlu, Volkan Karaman, Güven Toksoy, Birsen Karaman, Seher Başaran, Oya Uyguner, ve Gözde Yeşil Sayın. “CLINICAL AND MOLECULAR RESULTS OF SIX CASES WITH ROBERTS SYNDROME: REVIEW OF CASES FROM TURKIYE”. Journal of Istanbul Faculty of Medicine 85, sy. 4 (Ekim 2022): 501-9.
EndNote Aslanger AD, Kalayci T, Konur EN, Güleç Ç, Avcı Ş, Altunoğlu U, Karaman V, Toksoy G, Karaman B, Başaran S, Uyguner O, Yeşil Sayın G (01 Ekim 2022) CLINICAL AND MOLECULAR RESULTS OF SIX CASES WITH ROBERTS SYNDROME: REVIEW OF CASES FROM TURKIYE. Journal of Istanbul Faculty of Medicine 85 4 501–509.
IEEE A. D. Aslanger, “CLINICAL AND MOLECULAR RESULTS OF SIX CASES WITH ROBERTS SYNDROME: REVIEW OF CASES FROM TURKIYE”, İst Tıp Fak Derg, c. 85, sy. 4, ss. 501–509, 2022.
ISNAD Aslanger, Ayça Dilruba vd. “CLINICAL AND MOLECULAR RESULTS OF SIX CASES WITH ROBERTS SYNDROME: REVIEW OF CASES FROM TURKIYE”. Journal of Istanbul Faculty of Medicine 85/4 (Ekim 2022), 501-509.
JAMA Aslanger AD, Kalayci T, Konur EN, Güleç Ç, Avcı Ş, Altunoğlu U, Karaman V, Toksoy G, Karaman B, Başaran S, Uyguner O, Yeşil Sayın G. CLINICAL AND MOLECULAR RESULTS OF SIX CASES WITH ROBERTS SYNDROME: REVIEW OF CASES FROM TURKIYE. İst Tıp Fak Derg. 2022;85:501–509.
MLA Aslanger, Ayça Dilruba vd. “CLINICAL AND MOLECULAR RESULTS OF SIX CASES WITH ROBERTS SYNDROME: REVIEW OF CASES FROM TURKIYE”. Journal of Istanbul Faculty of Medicine, c. 85, sy. 4, 2022, ss. 501-9.
Vancouver Aslanger AD, Kalayci T, Konur EN, Güleç Ç, Avcı Ş, Altunoğlu U, Karaman V, Toksoy G, Karaman B, Başaran S, Uyguner O, Yeşil Sayın G. CLINICAL AND MOLECULAR RESULTS OF SIX CASES WITH ROBERTS SYNDROME: REVIEW OF CASES FROM TURKIYE. İst Tıp Fak Derg. 2022;85(4):501-9.

Contact information and address

Addressi: İ.Ü. İstanbul Tıp Fakültesi Dekanlığı, Turgut Özal Cad. 34093 Çapa, Fatih, İstanbul, TÜRKİYE

Email: itfdergisi@istanbul.edu.tr

Phone: +90 212 414 21 61