First preimplantation genetic testing case of Meckel syndrome with a novel homozygous TXNDC15 variant in a non‐consanguineous Chinese family

Abstract

AbstractBackgroundMeckel–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.MethodsLow‐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.ResultsA 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.ConclusionThis 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.