Marwa Daghsni, Elizabeth Sheehan, Suneeta Madan-Khetarpal, Mahmoud Aarabi, Selma F. Witchel, Aleksandar Rajkovic, Svetlana A. Yatsenko
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In this report, we provide clinical outcomes, inheritance, and clinical implications of derX in three families referred to diagnostic testing due to discrepant results for sex chromosomes reported by cfDNA, abnormal prenatal ultrasound findings, recurrent pregnancy losses, or affected family members with derX transmitted through multiple generations. Reports of discrepant sex and risk for sex chromosome aneuploidy such as 45,X, 47,XXY and 47,XYY are common false positive outcomes of a prenatal cfDNA screening if either a mother or a fetus has unbalanced Xp-Yq translocation. In addition, mothers who carry der(X) facing a recurrent risk of ambiguity in prenatal testing. Pregnancy loss and neonatal death/stillbirth of male offspring are common in affected families, but this risk does not directly correlate with the size of deleted Xp region. 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引用次数: 0
摘要
X 染色体和 Y 染色体之间的不平衡易位是一种常见的染色体重排。衍生 X 染色体(derX)的存在,即 Yq11-qter 染色体片段连接到 X 染色体的短臂上,取代了末端的 Xpter-p22.31,给解读产前无细胞 DNA(cfDNA)筛查结果、建立男性和女性个体的基因型-表型相关性以及遗传咨询带来了挑战。在本报告中,我们提供了因 cfDNA 报告的性染色体结果不一致、产前超声检查结果异常、反复妊娠失败或受影响的家族成员通过多代传递 derX 而转诊进行诊断检测的三个家庭中 derX 的临床结果、遗传和临床意义。如果母亲或胎儿存在不平衡的 Xp-Yq 易位,产前 cfDNA 筛查中常见的假阳性结果是报告性染色体不一致和性染色体非整倍体风险,如 45,X、47,XXY 和 47,XYY。此外,携带der(X)的母亲在产前检测中经常面临不明确的风险。在受影响的家族中,妊娠失败和新生儿死亡/死产男性后代的情况很常见,但这种风险与删除 Xp 区域的大小并无直接关系。这项研究强调了 CMA 和家族检测对准确诊断和遗传咨询的重要性。
Recurrent Xp22.31-Yq11 Unbalanced Translocations: Molecular Diagnosis and Clinical Implications in Three Families
Unbalanced translocation between chromosomes X and Y is a recurring chromosomal rearrangement. The presence of a derivative chromosome X (derX), where a Yq11-qter segment is attached to the short arm of chromosome X, replacing a terminal Xpter-p22.31, poses challenges for interpretation of findings by prenatal cell-free DNA (cfDNA) screening, establishing genotype–phenotype correlation in male and female individuals, and for genetic counseling. In this report, we provide clinical outcomes, inheritance, and clinical implications of derX in three families referred to diagnostic testing due to discrepant results for sex chromosomes reported by cfDNA, abnormal prenatal ultrasound findings, recurrent pregnancy losses, or affected family members with derX transmitted through multiple generations. Reports of discrepant sex and risk for sex chromosome aneuploidy such as 45,X, 47,XXY and 47,XYY are common false positive outcomes of a prenatal cfDNA screening if either a mother or a fetus has unbalanced Xp-Yq translocation. In addition, mothers who carry der(X) facing a recurrent risk of ambiguity in prenatal testing. Pregnancy loss and neonatal death/stillbirth of male offspring are common in affected families, but this risk does not directly correlate with the size of deleted Xp region. This study emphasizes the importance of CMA and familial testing for accurate diagnosis and genetic counseling.
期刊介绍:
The American Journal of Medical Genetics - Part A (AJMG) gives you continuous coverage of all biological and medical aspects of genetic disorders and birth defects, as well as in-depth documentation of phenotype analysis within the current context of genotype/phenotype correlations. In addition to Part A , AJMG also publishes two other parts:
Part B: Neuropsychiatric Genetics , covering experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders.
Part C: Seminars in Medical Genetics , guest-edited collections of thematic reviews of topical interest to the readership of AJMG .