PDF(Pubmed)
Abstract：
BACKGROUND: Meckel-Gruber syndrome (MKS) is a perinatally lethal, genetically heterogeneous, autosomal recessive condition caused by defective primary cilium formation. So far, the association of TXNDC15-related MKS has been reported in only five independent families from diverse ethnic origins, including Saudi, Pakistani, Estonian, and Indian. Here, we report a fetus diagnosed with MKS at 12 weeks, exhibiting typical ultrasound findings.
METHODS: Low-coverage whole-genome sequencing was used to identify chromosomal abnormalities. Trio-base whole exome sequencing (trio-WES) was performed to investigate the potential pathogenic variants associated with MKS. Preimplantation genetic testing for monogenic disorders (PGT-M) was applied to prevent the transmission of the pathogenic variant.
RESULTS: A novel homozygous pathogenic variant in the TXNDC15 gene was identified through trio-WES. The application of PGT-M successfully prevented the transmission of the pathogenic variant and resulted in an ongoing pregnancy.
CONCLUSIONS: This is the first report of a TXNDC15 variant in the Chinese population and the first PGT case of TXNDC15-related MKS worldwide. The successful application of PGT-M in this family provides a potential approach for other monogenic diseases. Our case expands the variant spectrum of TXNDC15 and contributes to the molecular diagnosis and genetic counseling for MKS. This case underscores the importance of appropriate genetic testing methods and accurate genetic counseling in the diagnosis of rare monogenic diseases.
METHODS: Low-coverage whole-genome sequencing was used to identify chromosomal abnormalities. Trio-base whole exome sequencing (trio-WES) was performed to investigate the potential pathogenic variants associated with MKS. Preimplantation genetic testing for monogenic disorders (PGT-M) was applied to prevent the transmission of the pathogenic variant.
RESULTS: A novel homozygous pathogenic variant in the TXNDC15 gene was identified through trio-WES. The application of PGT-M successfully prevented the transmission of the pathogenic variant and resulted in an ongoing pregnancy.
CONCLUSIONS: This is the first report of a TXNDC15 variant in the Chinese population and the first PGT case of TXNDC15-related MKS worldwide. The successful application of PGT-M in this family provides a potential approach for other monogenic diseases. Our case expands the variant spectrum of TXNDC15 and contributes to the molecular diagnosis and genetic counseling for MKS. This case underscores the importance of appropriate genetic testing methods and accurate genetic counseling in the diagnosis of rare monogenic diseases.
摘要：
背景：Meckel-Gruber综合征（MKS）是围产期致死性，遗传异质性，由原发性纤毛形成缺陷引起的常染色体隐性条件。到目前为止,仅在来自不同种族血统的五个独立家庭中报道了TXNDC15相关MKS的关联，包括沙特,巴基斯坦,爱沙尼亚语,和印度人。这里,我们报告胎儿在12周时被诊断为MKS,表现出典型的超声检查结果。
方法：使用低覆盖全基因组测序来鉴定染色体异常。进行三碱基全外显子组测序（trio-WES）以研究与MKS相关的潜在致病变异。应用单基因疾病的植入前遗传测试（PGT-M）来防止致病性变体的传播。
结果：通过trio-WES鉴定了TXNDC15基因中的新型纯合致病变异体。PGT-M的应用成功地防止了致病变体的传播，并导致了持续的妊娠。
结论：这是中国人群中首次报道TXNDC15变异体，也是全球首例TXNDC15相关MKS的PGT病例。PGT-M在该家族中的成功应用为其他单基因疾病提供了潜在的途径。我们的案例扩展了TXNDC15的变异谱，并有助于MKS的分子诊断和遗传咨询。该病例强调了适当的基因检测方法和准确的遗传咨询在罕见单基因疾病诊断中的重要性。
方法：使用低覆盖全基因组测序来鉴定染色体异常。进行三碱基全外显子组测序（trio-WES）以研究与MKS相关的潜在致病变异。应用单基因疾病的植入前遗传测试（PGT-M）来防止致病性变体的传播。
结果：通过trio-WES鉴定了TXNDC15基因中的新型纯合致病变异体。PGT-M的应用成功地防止了致病变体的传播，并导致了持续的妊娠。
结论：这是中国人群中首次报道TXNDC15变异体，也是全球首例TXNDC15相关MKS的PGT病例。PGT-M在该家族中的成功应用为其他单基因疾病提供了潜在的途径。我们的案例扩展了TXNDC15的变异谱，并有助于MKS的分子诊断和遗传咨询。该病例强调了适当的基因检测方法和准确的遗传咨询在罕见单基因疾病诊断中的重要性。
