Otizm Spektrum Bozukluğu Olan Monozigotik İkizlerde Tüm Genom Dizileme Çalışması

Abstract

ÖZ Amaç: Nörogelişimsel bozukluğun en bilinen türü olan Otizm Spektrum Bozukluğu (OSB), bir zihinsel gelişim bozukluğudur. OSB için kesin bir biyobelirteç olmadığından, hastanın davranışının değerlendirilmesine dayalı olarak tanı konmaktadır. OSB'de davranışsal ve sosyal bozuklukların yanı sıra genetik faktörler de önemlidir. Gereç ve Yöntem: Çalışmada, iki monozigotik ikiz çiftinin (biri uyumsuz diğeri uyumlu) klinik özelliklerinin değerlendirilmesinin yanı sıra, Tüm genom dizileme (WGS) yöntemi ile genetik anormallikler incelenmiştir. Bulgular: WGS sonuçlarına göre, 29 yeni aday gende 13 yüksek patojenik varyant tespit edilmiştir. Aday genler MEAF6, OR2T8, ABI2, PDE4D, GLIS3, DRD4, LPXN, FAM186A, NEK3, GOLGA8A, SSC5D, ARMCX4, ADAR, LRP1B, DAP, LYRM7, MUC12, CNTNAP3B, TCP11L1, DRD4, ORRC3B ve TCP11L1, ORRC3B’i içermektedir. Sonuç: OSB'li bireylerde ve ailelerinde hastalığın anlaşılmasında klinik değerlendirmelerin ve genetik değişikliklerin incelenmesinin önemli olduğunu düşünmekteyiz.

Keywords

• Otizm spektrum bozukluğu
• MZ ikizler
• Tüm genom dizileme (WGS)
• Genetik

The Study of Whole Genome Sequencing in Monozygotic Twins with Autism Spectrum Disorder

Abstract

Objective: Autism spectrum disorder (ASD), the most well-known type of neurodevelopmental disorder, is a mental development disorder. Since there is no definitive biomarker for ASD, diagnosis is made based on the assessment of the patient's behavior. In addition to behavioral and social disorders, genetic factors are also important in ASD.

Materials and Methods: In the study, variant analyses were performed by whole genome sequencing (WGS) method, as well as evaluating the clinical features of two monozygotic twin couples (one discordant and the other concordant).

Results: According to the WGS results, thirteen high pathogenic variants were detected in twenty-nine novel candidate genes. Candidate genes include MEAF6, OR2T8, ABI2, PDE4D, GLIS3, DRD4, LPXN, FAM186A, NEK3, GOLGA8A, SSC5D, ARMCX4, ADAR, LRP1B, DAP, LYRM7, MUC12, CNTNAP3B, TCP11L1, OR8B3, KLRC3, and DPP9.

Conclusion: We speculate that clinical evaluations and examination of genetic changes are important for understanding the disease in individuals with ASD and their families.

Keywords

• Autism spectrum disorder
• MZ twins
• Whole genome sequencing (WGS)
• Genetics

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