Optimized trio genome sequencing (OTGS) as a first-tier genetic test in critically ill infants: practice in China.,Human Genetics

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Optimized trio genome sequencing (OTGS) as a first-tier genetic test in critically ill infants: practice in China.
Human Genetics ( IF 3.8 ) Pub Date : 2020-01-21 , DOI: 10.1007/s00439-019-02103-8
Huijun Wang ₁ , Yulan Lu ₁ , Xinran Dong ₁ , Guoping Lu ₂ , Guoqiang Cheng ₃ , Yanyan Qian ₁ , Qi Ni ₁ , Ping Zhang ₁ , Lin Yang ₁ , Bingbing Wu ₁ , Wenhao Zhou _{1,

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Affiliation

Genome sequencing is used to make genetic diagnoses in critically ill infants with rapid turnaround time (TAT). Herein, to delineate the value of a genetic diagnosis, we provide the results from 130 pediatric patients in a large, comprehensive children's hospital in China. This study was performed using an optimized trio genome sequencing (OTGS) test. The sequencing depth for patients was 40-50 × and for their parents, it was 8-10 × . Patients from the pediatric or neonatal intensive care unit (PICU/NICU) with complicated clinical features were enrolled between June 2018 and December 2018, each with a phenotype suggesting an underlying genetic disorder. OTGS testing identified pathogenic variants in 62 of 130 individuals, resulting in a diagnosis rate of 47.7%. The TAT varied from 72 to 120 h, with an average of 94 h and a median of 90 h. Of the 62 infants with diagnoses, 48 (77.4%) had pathogenic single-nucleotide variants (SNVs), 12 (19.4%) had pathogenic copy number variations (CNVs) or structure variants (SVs), and 2 (3.2%) had small deletions in one allele plus pathogenic variants in another allele of autosomal recessive genes. Therapeutic strategies for 48.4% (30/62) of the diagnosed patients were modified and included transplantation, dietary recommendations, or change of drugs, which avoided morbidity and improved prognosis. This study provided high-capacity OTGS testing in detecting SNVs and chromosomal abnormalities with fast response, higher diagnostic yield, and lower cost. OTGS demonstrates the potential to be the first-tier of genetic testing used in critically ill infants in developing countries.

更新日期：2020-03-26

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