TRAPPopatili Olgularda Klinik, Radyolojik ve Moleküler Bulgular

Öz

Amaç: Vezikül trafiği ile ilişkili Taşıyıcı Protein Parçacıklarında (TRAPP) meydana gelen patolojiler TRAPPopatiler olarak adlandırılan nadir hastalıklardır. Bu çalışmanın amacı, bir TRAPPopati vaka serisini sunmak, klinik ve moleküler bulguları tanımlamak ve ayrıca vakalarımızı Türkiye’den bildirilen diğer vakalarla birlikte gözden geçirmektir. Gereç ve Yöntem: Mart 2018-Mart 2020 tarihleri arasında Bezmialem Vakıf Üniversitesi Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı’na sevk edilen mikrosefali, epilepsi, kas distrofisi ve zihinsel yetersizlik gibi nörolojik bulguları olan olgular bu çalışma için gözden geçirildi. Fenotipi bilinen veya henüz herhangi bir insan hastalığı ile ilişkili olmayan TRAPP kompleks familyasına sahip genlerde patojenik varyantları olan hastalar çalışmaya dahil edildi. Klinik, radyolojik ve tüm ekzom dizilerinden elde edilen moleküler bulgular yeniden değerlendirildi. Bulgular: Nöromotor retardasyon, nöbet, postnatal mikrosefali ve serebral-serebellar atrofili Olgu 1’de TRAPPC4 geninde (NM_016146.5) homozigot c.454+3A>G p.(?) varyantı, epilepsi, postnatal mikrosefali, nöromotor retardasyon ve otizmi olan Olgu 2’de TRAPPC6B geninde (NM_001079537.1) homozigot daha önce bildirilmemiş yeni c.57C>G p.(Try19Ter) varyantı ile musküler distrofi, katarakt, nöromotor retardasyon and mikrosefalili Olgu 3’te TRAPPC11 geninde (NM_021942.5) homozigot c.2938G>A p. (Gly980Arg) varyantı saptandı. Sonuç: Bu çalışma, TRAPPopatilerde yeni tanımlanan genlerin mikrosefali, gelişimsel gecikme, epilepsi, zihinsel yetersizlik, serebral-serebellar atrofi ve otizm bulgularından sorumlu olduğunu göstermiştir. TRAPP ailesindeki genler birbirinden bağımsız çalışsa da bu gruptaki hastalıklara fenotipleri örtüştüğü için TRAPPopatiler adı verilir. Çalışmamızda klinik bulguların tartışılması ve Türkiye’deki TRAPP ailesindeki genlerin mutasyon profilinin özetlenmesi amaçlanmıştır.

Anahtar Kelimeler

• Mikrosefali
• TRAPPopati
• nadir hastalıklar

Clinical, Radiological, and Molecular Findings in Cases with TRAPPopathies

Öz

Objective: Pathologies occurring in Transport Protein Particles (TRAPP) involved in vesicular traffic are rare diseases called TRAPPopathies. The aim of this study was to present a case series of TRAPPopathies, to describe the clinical and molecular findings, and additionally to review our cases together with other cases reported from Turkiye. Materials and Methods: Patients with neurological findings such as microcephaly, epilepsy, muscular dystrophy, and intellectual disability who were referred to Bezmialem Vakıf University, Faculty of Medicine, Department of Medical Genetics between March 2018 and March 2020 were reviewed for this study. Patients with pathogenic variants in genes with TRAPP complex family with known phenotype or not yet associated any human disease were included in the study. Clinical, radiological, and molecular findings obtained by whole exome sequences of cases were re-evaluated. Results: Molecular analysis revealed homozygous c.454+3A>G p.(?) variant in TRAPPC4 (NM_016146.5) gene in Case 1 with neuromotor retardation, intractable seizures, postnatal microcephaly, and cerebralcerebellar atrophy, homozygous novel c.57C>G p.(Try19Ter) variant in TRAPPC6B (NM_001079537.1) in Case 2 with epilepsy, postnatal microcephaly, severe neuromotor retardation, and autism, and homozygous c.2938G>A p.(Gly980Arg) variant in TRAPPC11 (NM_021942.5) gene in Case 3 with muscular dystrophy, cataract, neuromotor retardation, and microcephaly. Conclusion: This study showed that newly identified genes in TRAPPopathies are responsible for microcephaly, developmental delay, epilepsy, intellectual disability, cerebral-cerebellar atrophy, and autism. Although the genes in the TRAPP family work independently of each other, the diseases in this group are called TRAPPopathies because their phenotypes overlap. The aim of our study was to discuss the clinical findings and to summarize the mutation profile of the genes in the TRAPP family in Turkiye.

Anahtar Kelimeler

• Microcephaly
• rare diseases
• TRAPPopathies

Kaynakça

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