Targeted gene panel sequencing prenatally detects two novel mutations of DYNC2H1 in a fetus with increased biparietal diameter and polyhydramnios

Abstract

This is the first report of prenatal diagnosis of DYNC2H1 mutations causing SRPS Type III in a fetus with increased BPD associated with polyhydramnios in China. Our findings expand the mutation spectrum of DYNC2H1 in this rare disease and demonstrate that targeted gene panel capture followed by next-generation sequencing (NGS) is an efficient and cost-effective method to perform a molecular prenatal diagnosis of a rare genetic skeletal disorder.

Prenatal diagnosis of skeletal dysplasias using a targeted skeletal gene panel

“…The skeletal gene panel sequencing provided a diagnosis of specific skeletal disorders with identification of the following genes: FGFR3 , COL1A2 , and IHH , revealing a novel de novo likely pathogenic variant in the COL2A1 gene. One fetus had novel compound heterozygous variants in DYNC2H1 with one nonsense variant and another missense variant, which were described in our recent study …”

“…One fetus had novel compound heterozygous variants in DYNC2H1 with one nonsense variant and another missense variant, which were described in our recent study. 22 The molecular genetic diagnostic rates in the current study are on the higher end of prenatal yields (10/12 affected fetuses, 83%), with 8 definitive molecular diagnoses and 2 possible molecular diagnoses, confirming that proband-only skeletal panel sequencing is highly sensitive for prenatal diagnosis in a selected group of affected fetuses with antenatal evidence of skeletal anomalies that are based on an ultrasound evaluation and who failed to receive a diagnosis with standard genetic testing (karyotyping and microarray). Recent studies recommended the utility of prenatal wholeexome sequencing (WES) for diagnosis of structurally abnormal fetuses, with diagnostic rates varying between 6.2% and 81%.…”

Prenatal diagnosis of micrognathia in 41 fetuses: Retrospective analysis of outcome and genetic etiologies

“…Targeted gene panel sequencing is particularly useful in genetically heterogeneous conditions. Some teams have already used this approach in utero for cases with hydrops fetalis (Sudrié-Arnaud et al, 2018) or with skeletal dysplasia (Deng et al, 2018). The application of this strategy to fetal micrognathia, with a panel including all collagen genes involved in Stickler syndrome and genes associated with syndromic forms, is conceivable.…”

Gendiagnostik in der Geburtshilfe – klares Konzept, verständliche ärztliche Beratung

“…Die UPD-Diagnostik basiert wie die MLPA auf rein molekulargenetischen Methoden und dient dem Nachweis chromosomaler Imprintingstörungen [88]. Genveränderungen werden mittels PCR [89], Sanger-Sequenzierung [90], MLPA und Panel-Diagnostik [91] erfasst. Mit der MLPA lassen sich große DNA-Teilverluste und -Zugewinne eines einzelnen Gens nachweisen, die mit der Sanger-Sequenzierung und Panel-Diagnostik nicht zur Darstellung kommen.…”