Open AccessA prenatally diagnosed case of Meckel–Gruber syndrome with novel compound heterozygous pathogenic variants in the TXNDC15 gene
Author(s) -
Ridnõi Konstantin,
Šois Marek,
Vaidla Eve,
Pajusalu Sander,
Kelder Larissa,
Reimand Tiia,
Õunap Katrin
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.614
Subject(s) - compound heterozygosity , exome sequencing , genetics , prenatal diagnosis , genetic heterogeneity , polydactyly , gene , medicine , exon , biology , mutation , fetus , pregnancy , phenotype
Background Meckel–Gruber syndrome (MKS) is a well‐known rare disease that can be detected on prenatal ultrasound. Meckel–Gruber syndrome has very heterogeneous etiology; at least, 17 genes have been described in association with MKS. The characteristic findings in fetuses affected by MKS are encephalocele (usually occipital), postaxial polydactyly, and polycystic dysplastic kidneys. However, the association of the TXNDC15 gene with MKS has been reported only once before in three consanguineous families. Methods We report a new case of MKS diagnosed at 12 + 1 weeks of gestation with typical ultrasound findings, but with novel compound heterozygous pathogenic variants in the TXNDC15 gene identified by whole‐exome sequencing (WES). Results This is the second clinical report supporting TXNDC15 as a novel causative gene of MKS, and the first describing a case in a non‐consanguineous family with causative compound heterozygous mutations. Conclusions Meckel–Gruber syndrome is a very heterogeneous syndrome in terms of the associated causal genes. In the first‐line diagnosis, we used an next‐generation sequencing (NGS)‐based large gene panel, but only 10 MKS genes were available on the platform used. In the case of prenatal ultrasound findings that are highly suggestive of MKS and a negative NGS MKS gene panel, WES should also be performed to not miss rare gene associations.