46,XX,t(1;6;14) 染色体复杂易位的遗传学分析1 例

Genetic analysis of 46,XX,t(1;6;14) complex translocation ：A case report

摘要

报告1例因母源性染色体复杂易位的不孕病例，并系统阐述了其遗传学诊断与家系分析过程。患者为31 岁女性，因不孕就诊，病史长达 8 年，此前多项常规检查未能明确病因。为探究遗传学因素，对其进行高分辨染色体核型分析，结果显示，患者核型存在复杂重排，具体为46，XX，der（1）（pter →q12:: q32→q ter），der（6）（6pter→6q13：：14p13→14pter），der（14）（6qter→6q13：：1q12→1q32：：14p13→14qter），可简化为46，XX，t（1 ；6；14），提示涉及1、6、14号染色体的三向易位。为明确该异常核型的来源与遗传模式，进而对患者父母及妹妹进行家系染色体核型验证，分析发现其父亲（核型46，XY）与妹妹（核型46，XX）染色体未见异常，而其母亲的核型分析结果与患者完全一致[46，XX，t（1；6；14）]。据此，确诊患者所携带的异常核型源于其母亲，这很可能是导致其生育障碍的根本遗传学原因。本病例具有明确的临床启示：首先，对于临床表现为不明原因的不孕症患者，尤其是当常规检查无阳性发现时，进行系统的染色体核型分析是一项不可或缺的病因筛查手段，能够揭示潜在的染色体结构异常；其次，一旦检出异常核型，开展家系遗传学分析至关重要，不仅能追溯异常来源，还能明确遗传模式，为风险评估提供依据；最后，基于确切的遗传诊断，应为此类染色体易位携带者家庭提供以肧胎植人前遗传学检测（preimplantation genetic testing for，PGT）为核心的、专业的生育咨询与生殖干预指导，选择染色体正常的肧胎进行移植，从而有效阻断异常染色体结构的垂直传递，助力实现健康生育与优生优育目标。

Abstract

This report details the cytogenetic and familial investigation of a 31-year-old female presen- ting with primary infertility of eight years＇duration.Previous extensive evaluations，including assessment of hormonal profiles，tubal patency，and partner semen analysis，yielded no explanatory findings， prompting a genetic etiology workup.High-resolution G-banding chromosome analysis was subsequently performed.The patient＇s karyotype was characterized by a complex，apparently balanced，three-way re- arrangement involving chromosomes 1，6，and 14.The precise nomenclature was 46，XX，der（1）（pter- q12 ：：q32→qter），der（6）（6 pter → 6 q13 ::14 p13 → 14 pter），der（14）（6 qter → 6 q 13::1 q 12→1 q32 ：： 14p13→14 qter) ，formally interpreted as 46,XX,t(1;6;14).This result indicated a reciprocal translo- cation in which segments of chromosomes 1，6，and 14 were rearranged，resulting in three derivative chromosomes：der（1），der（6），and der（14）.To establish the inheritance pattern and provide accurate familial risk assessment，karyotypic analysis was extended to the proband＇s parents and her younger sister.Her father (46,XY) and sister (46,XX) were both found to have normal chromosomal constitu- tions.Crucially，her phenotypically normal mother was identified to carry an identical chromosomal re- arrangement： 46,XX,t(1;6;14).This confirmed a maternal origin and classified the mother as a balanced translocation carrier.The patient，inheriting this derivative chromosome complement，was thus also a balanced carrier.Her primary infertility，in the absence of a history of recurrent miscarriage，was highly likely attributable to this cytogenetic anomaly.The proposed mechanism is a markedly increased risk of producing gametes with unbalanced chromosomal segregation during meiosis，leading to conceptions with lethal aneuploidy or subviable genomic imbalances that precluded successful implantation or result in very early，undetected pregnancy loss.This case highlights several critical principles in reproductive genetics. First，it reaffirms that conventional karyotype analysis remains a fundamental and indispensable diagnostic tool in the evaluation of idiopathic primary infertility，capable of revealing cryptic balanced structural re-arrangements that are not detectable by molecular karyotyping（chromosomal microarray）.Second，it un- derscores the absolute necessity of systematic familial cytogenetic studies following the identification of an index case.Such studies are vital for distinguishing de novo from inherited rearrangements，providing precise recurrence risk quantification，and enabling comprehensive genetic counseling for all at-risk fami- ly members.Finally，for identified carriers of such translocations seeking biological parenthood，preim- plantation genetic testing（PGT）for structural rearrangements represents the cornerstone of modern repro- ductive management.PGT allows for the selective transfer of embryos with a balanced or normal chromo- somal complement，thereby offering a direct pathway to a healthy live birth while effectively preventing the intergenerational transmission of the chromosomal anomaly.This case also suggests the need for fur- ther investigation into whether the specific breakpoints in such complex rearrangements may disrupt genes critical for fertility，potentially explaining the phenotypic presentation of infertility in the absence of spon- taneous abortion.

关键词

染色体复杂易位 / 核型分析 / 遗传学分析

Key words

Complex chromosomal translocation / Karyotype analysis / Genetic analysis

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