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Background: Genetic skeletal disorders (GSDs) are clinically and genetically heterogeneous with more than 350 genes accounting for the diversity of disease phenotypes. Prenatal diagnosis of these disorders has been challenging because of the limited but variable prenatal phenotypes, highlighting the need of a novel genetic approach. Short-rib polydactyly syndrome (SRPS) Type III is an autosomal recessive GSD characterized by extreme narrowness of the thorax, severely shortened tubular bones, polydactyly and multiple malformations., Methods: Cytogenetic and molecular analyses using GTG-banding, single nucleotide polymorphism array and a novel GSDs targeted gene panel sequencing were performed in a 24 weeks fetus with increased biparietal diameter (BPD), short limbs, narrow thorax and polyhydramnios., Results: No chromosomal abnormalities and pathogenic copy number variations (CNVs) were detected in the fetus. Two novel compound heterozygous mutations c.2992C > T and c.12836G > C in the DYNC2H1 gene were identified by targeted genes panel sequencing. A literature review was performed to delineate the prenatal phenotype of SRPS Type III., Conclusion: 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., (© 2018 Wiley Periodicals, Inc.)

Metabolic disorders are inborn errors that often present in the neonatal period with a devastating clinical course. If not treated promptly, these diseases can result in severe, irreversible disease or death. Determining the molecular defects in metabolic diseases is important in providing a definitive diagnosis for patient management. Therefore, prenatal diagnosis for families with known mutations causing metabolic disorders is crucial for timely intervention. Here we present three families in which standard Sanger sequencing failed to provide a definitive diagnosis, but the detection of genomic deletions by array comparative genomic hybridization (CGH) specifically targeted to mitochondrial and metabolic disease genes, MitoMet®, was fundamental in providing accurate prenatal diagnosis. In addition, to our knowledge, two deletions are the smallest detected by oligonucleotide array CGH reported for their respective genes, OTC and ARG1. These data highlight the importance of targeted array CGH in patients with suspected metabolic disorders and incomplete or negative sequencing results, as well as its emerging role in prenatal diagnosis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Genetic skeletal disorders (GSDs) are clinically and genetically heterogeneous with more than 350 genes accounting for the diversity of disease phenotypes. Prenatal diagnosis of these disorders has been challenging because of the limited but variable prenatal phenotypes, highlighting the need of a novel genetic approach. Short‐rib polydactyly syndrome (SRPS) Type III is an autosomal recessive GSD characterized by extreme narrowness of the thorax, severely shortened tubular bones, polydactyly and multiple malformations. Methods: Cytogenetic and molecular analyses using GTG‐banding, single nucleotide polymorphism array and a novel GSDs targeted gene panel sequencing were performed in a 24 weeks fetus with increased biparietal diameter (BPD), short limbs, narrow thorax and polyhydramnios. Results: No chromosomal abnormalities and pathogenic copy number variations (CNVs) were detected in the fetus. Two novel compound heterozygous mutations c.2992C > T and c.12836G > C in the DYNC2H1 gene were identified by targeted genes panel sequencing. A literature review was performed to delineate the prenatal phenotype of SRPS Type III. Conclusion: 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. [ABSTRACT FROM AUTHOR]