关键词: 染色体复杂易位, 核型分析, 遗传学分析

Abstract:

This report details the cytogenetic and familial investigation of a 31-year-old female presenting 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)(6pter→6q13:: 14p13→14pter), der(14)(6qter→6q13:: 1q12→1q32:: 14p13→14qter), formally interpreted as 46, XX, t(1;6;14). This result indicated a reciprocal translocation 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 constitutions. 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 rearrangements that are not detectable by molecular karyotyping (chromosomal microarray). Second, it underscores 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 family members. Finally, for identified carriers of such translocations seeking biological parenthood, preimplantation genetic testing (PGT) for structural rearrangements represents the cornerstone of modern reproductive management. PGT allows for the selective transfer of embryos with a balanced or normal chromosomal 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 further 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 spontaneous abortion.

Key words: Complex chromosomal translocation, Karyotype analysis, Genetic analysis