Clinical, Radiological, and Molecular Findings in Cases with TRAPPopathies

Ayça Dilruba Aslanger; Esma Şengenç; Emrah Yücesan; Beyza Göncü; Akın İşcan; Gözde Yeşil Sayın

Makale detayları

Clinical, Radiological, and Molecular Findings in Cases with TRAPPopathies

Yazarlar:

Ayça Dilruba Aslanger | Esma Şengenç | Emrah Yücesan | Beyza Göncü | Akın İşcan | Gözde Yeşil Sayın

Yayıncı:

Istanbul University

Ana Başlıklar:

Çocuk Sağlığı ve Hastalıkları

Dergi:

Çocuk Dergisi Vol.23 Issue 3, pp.203-209

Belge Tipi:

Makale

Yayın Tarihi:

10/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001303675

pISSN:

1308-8491

Anahtar kelimeler:

Özet:

 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.4543AG p.? variant in TRAPPC4 NM_016146.5 gene in Case 1 with neuromotor retardation, intractable seizures, postnatal microcephaly, and cerebralcerebellar atrophy, homozygous novel c.57CG p.Try19Ter variant in TRAPPC6B NM_001079537.1 in Case 2 with epilepsy, postnatal microcephaly, severe neuromotor retardation, and autism, and homozygous c.2938GA 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.

 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.4543AG p.? variant in TRAPPC4 NM_016146.5 gene in Case 1 with neuromotor retardation, intractable seizures, postnatal microcephaly, and cerebralcerebellar atrophy, homozygous novel c.57CG p.Try19Ter variant in TRAPPC6B NM_001079537.1 in Case 2 with epilepsy, postnatal microcephaly, severe neuromotor retardation, and autism, and homozygous c.2938GA 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.

 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.4543AG p.? variant in TRAPPC4 NM_016146.5 gene in Case 1 with neuromotor retardation, intractable seizures, postnatal microcephaly, and cerebralcerebellar atrophy, homozygous novel c.57CG p.Try19Ter variant in TRAPPC6B NM_001079537.1 in Case 2 with epilepsy, postnatal microcephaly, severe neuromotor retardation, and autism, and homozygous c.2938GA 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.

 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 Türkiyeden bildirilen diğer vakalarla birlikte gözden geçirmektir. Gereç ve Yöntem: Mart 2018-Mart 2020 tarihleri arasında Bezmialem Vakıf Üniversitesi Tıp Fakültesi, Tıbbi Genetik Anabilim Dalına 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 1de TRAPPC4 geninde NM_016146.5 homozigot c.4543AG p.? varyantı, epilepsi, postnatal mikrosefali, nöromotor retardasyon ve otizmi olan Olgu 2de TRAPPC6B geninde NM_001079537.1 homozigot daha önce bildirilmemiş yeni c.57CG p.Try19Ter varyantı ile musküler distrofi, katarakt, nöromotor retardasyon and mikrosefalili Olgu 3te TRAPPC11 geninde NM_021942.5 homozigot c.2938GA 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 Türkiyedeki TRAPP ailesindeki genlerin mutasyon profilinin özetlenmesi amaçlanmıştır.

Makale detayları

Clinical, Radiological, and Molecular Findings in Cases with TRAPPopathies

Yazarlar:

Ayça Dilruba Aslanger | Esma Şengenç | Emrah Yücesan | Beyza Göncü | Akın İşcan | Gözde Yeşil Sayın

Yayıncı:

Istanbul University

Ana Başlıklar:

Çocuk Sağlığı ve Hastalıkları

Dergi:

Çocuk Dergisi Vol.23 Issue 3, pp.203-209

Belge Tipi:

Makale

Yayın Tarihi:

10/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001303675

pISSN:

1308-8491

Microcephaly

rare diseases

TRAPPopathiesMikrosefali

TRAPPopati

nadir hastalıklar

Sayı

Makale detayları

Clinical, Radiological, and Molecular Findings in Cases with TRAPPopathies

Yazarlar: Ayça Dilruba Aslanger | Esma Şengenç | Emrah Yücesan | Beyza Göncü | Akın İşcan | Gözde Yeşil Sayın

Yayıncı: Istanbul University

Ana Başlıklar: Çocuk Sağlığı ve Hastalıkları

Dergi: Çocuk Dergisi Vol.23 Issue 3, pp.203-209

Belge Tipi: Makale

Yayın Tarihi: 10/2023

Belge Dili: İngilizce

Document ID (Org No.): 2001303675

pISSN: 1308-8491

Microcephaly

rare diseases

TRAPPopathiesMikrosefali

TRAPPopati

nadir hastalıklar

Sayı

Yazarlar:

Ayça Dilruba Aslanger | Esma Şengenç | Emrah Yücesan | Beyza Göncü | Akın İşcan | Gözde Yeşil Sayın

Yayıncı:

Istanbul University

Ana Başlıklar:

Çocuk Sağlığı ve Hastalıkları

Dergi:

Çocuk Dergisi Vol.23 Issue 3, pp.203-209

Belge Tipi:

Makale

Yayın Tarihi:

10/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001303675

pISSN:

1308-8491