SPONDİLOEPİ (META) FİZYAL DİSPLAZİ ÖN TANILI BEŞ TÜRK ERKEK HASTADAKİ GENETİK ETYOLOJİNİN ARAŞTIRILMASI

Year 2023, , 184 - 189, 05.04.2023

Hamıde Betul Gerik Celebi , Sırrı Çam

https://doi.org/10.18229/kocatepetip.1061617

Abstract

AMAÇ: İskelet displazisi orantısız boy kısalığı ve çeşitli ortopedik komplikasyonlarla karakterize kompleks bir hastalık grubudur. X'e Bağlı Spondiloepifizyal Displazi Tarda, progresif spondiloepi(meta)fizyal displazi ve prematür osteoartritin eşlik ettiği X'e bağlı kalıtsal bir iskelet displazisidir. Trafficking protein particle complex 2 (TRAPPC2) geni bu hastalıkla ilişkilendirilmiştir. Progresif psödoromatoid displazi (PPRD), dirsek eklemlerinde genişleme ve artrit benzeri bulgular ile karakterize bir hastalıktır. Otozomal resesif kalıtımlı bir iskelet displazisi subgrubu olan bu hastalığa ise 6q21 kromozomal lokasyonunda bulunan celluler communication network factor 6 (CCN6) genindeki mutasyonlar neden olur. Bu çalışma ile X'e bağlı ya da otozomal resesif kalıtım paterni düşünülen, yıllardır tanı almamış beş erkek bireye tanı koyarak, olası tedavileri belirlemek ve prenatal preimplantasyon genetik test olanağı sunmak amaçlandı.
GEREÇ VE YÖNTEM: Bu çalışmaya, X'e bağlı veya otozomal resesif kalıtımlı iskelet displazisi olan beş erkek kardeş dahil edildi. Dört hastaya Whole Ekzom Sekanslama (WES) yapıldı. Bir hasta ve aynı aileden dört sağlıklı bireye ise Sanger sekanslama yapıldı.
BULGULAR: Etkilenen tüm kardeşlerde CCN6 geninde homozigot c.210C>A (p.Cys70Ter) ve c.302G>A (p.Gly101Glu) mutasyonları bulundu. Böylece, X'e bağlı resesif kalıtım paterni olma olasılığına rağmen WES sonrası otozomal resesif PPRD tanısı koyuldu.
SONUÇ: Bu çalışma normalde bir çocukluk çağı hastalığı olan Progresif psödoromatoid displazisi tanısı alan ortalama yaşı 54.6 olan en yaşlı hastaları sunmaktadır. p.Cys70Ter değişikliği Türk hastalarda en sık görülen patojenik varyanttır. Bu çalışma, Progresif psödoromatoid displazinin ortalama yaşam süresi üzerinde anlamlı bir etkisinin olmadığını göstermesi açısından da önemlidir. Aynı zamanda bu çalışma, bu hastalığın seyrini ve yaşam boyu eşlik edebilecek klinik bulguları göstermesi açısından da önemlidir.

Keywords

Artropati, ilerleyici psödoromatoid displazi, CCN6 geni

Supporting Institution

Manisa Celal Bayar Üniversitesi Rektörlüğü Bilimsel Araştırma Projeleri Koordinasyon Birimi

Project Number

2017-075

INVESTIGATION OF GENETIC ETIOLOGY IN FIVE TURKISH MALE PATIENTS WITH PRE-DIAGNOSED SPONDYLOEPI (META) PHYSEAL DYSPLASIA

Abstract

OBJECTIVE: Skeletal dysplasias is a complex disease group characterized by disproportionate short stature and various orthopedic complications. X-Linked Spondyloepiphyseal Dysplasia Tarda is an X-linked inherited skeletal dysplasia accompanied by progressive spondyloepi(meta)physeal dysplasia and premature osteoartritis. The gene related to the disorder is trafficking protein particle complex 2 (TRAPPC2). Progressive pseudorheumatoid dysplasia (PPRD) is characterized by enlargement of the elbow joints and arthritis-like findings. It is an autosomal recessive subtype of skeletal dysplasia caused by mutations in cellular communication network factor 6 (CCN6) gene located on chrosomal region 6q21. In this study, it was aimed to diagnose five male individuals with an X-linked or autosomal recessive inheritance pattern, who have not been diagnosed for years, to identify possible treatments and to offer prenatal pmreimplantation genetic testing.
MATERIAL AND METHODS: Five male siblings with skeletal dysplasia with an uncertain inheritance either X-linked or autosomal recessive pattern were included in this study, Whole Exome Sequencing (WES) was applied to the four affected cases. Sanger Sequencing was performed in one affected case and four healthy individuals.
RESULTS: Homozygous c.210C>A (p.Cys70Ter) and homozygous c.302G>A (p.Gly101Glu) mutations in the CCN6 gene were found in all affected siblings. Thus, the final diagnosis after WES was autosomal recessive PPRD despite the possibility of an X-linked recessive pattern.
CONCLUSIONS: This study presents a series of the oldest patients diagnosed with Progressive pseudorheumatoid dysplasia, normally a childhood disease, with an average age of 54.6. The p.Cys70Ter alteration is the most frequent pathogenic variant in Turkish patients. This study is also important in terms of showing that Progressive pseudorheumatoid dysplasia has no significant effect on life expectancy. At the same time, this study shows the progression of this disease and clinical findings that may accompany lifetime.

Keywords

Arthropathy, Progressive pseudorheumatoid dysplasia, CCN6 gene

Project Number

2017-075

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