探討Y染色體變異之臨床表現

Abstract

背景與動機： Y染色體因其高度重複且非重組的結構特性，在臨床產前遺傳診斷中具高度挑戰性。Small Y（長臂異染色質縮短）與鑲嵌型核型（如mos45,X/46,XY）等變異常引起胎兒表型疑慮與家屬焦慮。本文旨在釐清Y染色體結構變異的臨床意義與遺傳來源，建立整合性分析與諮詢流程，以提升產前診斷之準確性與溝通效率。 材料與方法： 本研究回溯分析2013至2023年間42例具Y染色體變異之胎兒羊膜穿刺檢體。分析工具使用核型分析、部分個案加做染色體微陣列（CMA）、進階追蹤使用FISH、MLPA與多色帶分析（mBAND），並進行父系核型追蹤，判定small Y之mos45,X/46,XY鑲嵌型變異之來源及臨床表現。 結果： small Y型態個案中92.59%為父系遺傳，其臨床表現將與父親相同，支持其屬良性染色體多型性；而mos45,X/46,XY個案則為自發性突變，結構組成複雜且需輔以進階分析工具進行詮釋。CMA未檢出結構異常，乃對Y染色體探針涵蓋不足，突顯技術侷限性。 結論： 本研究建立具系統性之Y染色體變異分析與諮詢架構，整合多項技術以提升診斷準確性。針對small Y型態，建議優先進行父系核型比對及超音波性別確認，以排除表型及影響。此整合流程有助於穩定孕婦情緒、促進臨床風險評估與家屬溝通成效。

Background and Motivation: Due to its highly repetitive and non-recombining structure, the Y chromosome presents significant challenges in clinical prenatal genetic diagnosis. Variants such as small Y (heterochromatin shortening of the long arm) and mosaic karyotypes (e.g., mos45,X/46,XY) often raise concerns regarding fetal phenotype and contribute to parental anxiety. This study aims to clarify the clinical significance and genetic origin of Y chromosome structural abnormalities, and to establish an integrated diagnostic and counseling workflow to improve the accuracy and efficiency of prenatal diagnosis. Materials and Methods: We retrospectively analyzed 42 amniocentesis cases with Y chromosome abnormalities collected between 2013 and 2023. Analytical methods included conventional karyotyping, with selected cases undergoing chromosomal microarray analysis (CMA), followed by advanced techniques such as fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), and multicolor banding (mBAND). Paternal karyotyping was also performed to determine the origin and clinical implications of small Y and mosaic mos45,X/46,XY variants. Results: Among the small Y cases, 92.59% were inherited from the father, who typically presented with normal phenotype and reproductive function, supporting their classification as benign chromosomal polymorphisms. In contrast, mos45,X/46,XY cases were de novo mutations with complex structural compositions requiring advanced techniques for accurate interpretation. No pathogenic structural abnormalities were detected by CMA; however, limited probe coverage for the Y chromosome highlighted the technical constraints of this platform. Conclusion: This study establishes a systematic framework for the analysis and counseling of Y chromosome variants by integrating multiple diagnostic approaches to enhance accuracy. For small Y cases, we recommend prioritizing paternal karyotype comparison and fetal ultrasound sex confirmation to rule out phenotypic effects. The proposed workflow contributes to emotional stabilization in pregnant individuals, facilitates clinical risk assessment, and improves communication with families.