Utility of next-generation sequencing in genetic testing and counseling of disorders involving the musculoskeletal system—trends observed from a single genetic unit

Journal of Orthopaedic Surgery and Research

Lekhangda Bhatnagar¹  Srinka Arora¹  Keerthi Konda Juturu¹  Vaishnavi Suresh¹  Gayatri R. Iyer¹  Qurratulain Hasan¹  Aruna Priya Kamireddy¹  Subhadra Poornima²  Akhilesh N. Pujar³  Roshan Kumar⁴  Sarah Bailur⁵  Prashant R. Utage⁶ 

[1] Department of Genetics and Molecular Medicine, Kamineni Hospitals, LB Nagar, 500 074, Hyderabad, Telangana, India;Department of Genetics, Credence Diagnostic Centre, Moula Ali, Hyderabad, India;Department of Ocular Genetics, LV Prasad Eye Institute, Banjara Hills, Hyderabad, India;Department of Orthopedics, Kamineni Hospitals, LB Nagar, Hyderabad, India;Department of Pediatrics, Kamineni Hospitals, LB Nagar, Hyderabad, India;Utage Child Neuro Clinic and Development Centre, Narayanguda, Hyderabad, India;

关键词: Musculoskeletal disorders;    Skeletal dysplasia;    Next-generation sequencing;    Genetic counseling;    Molecular diagnosis;   

DOI  :  10.1186/s13018-022-02969-x

来源: Springer

【 摘 要 】

BackgroundDisorders involving the musculoskeletal system are often identified with short stature and a range of orthopedic problems. The clinical and genetic heterogeneity of these diseases along with several characteristic overlaps makes definitive diagnosis difficult for clinicians. Hence, using molecular testing in addition to conventional tests becomes essential for appropriate diagnosis and management.MethodsComprehensive clinical examination, detailed pretest and posttest counseling, molecular diagnosis with next-generation sequencing (NGS), genotype–phenotype correlation and Sanger sequencing for targeted variant analysis.ResultsThis manuscript reports a molecular spectrum of variants in 34 orthopedic cases referred to a single genetic unit attached to a tertiary care hospital. The diagnostic yield of NGS-based tests coupled with genetic counseling and segregation analysis was 79% which included 7 novel variants. In about 53% (i.e. 18/34 cases), molecular testing outcome was actionable since 8 of the 18 underwent prenatal diagnosis, as they were either in their early gestation or had planned a pregnancy subsequent to molecular testing, while ten cases were premaritally/prenatally counseled for the families to take informed decisions as they were in the reproductive age.ConclusionsThe report highlights the importance of NGS-based tests even in a low resource setting as it helps patients, families and healthcare providers in reducing the economic, social and emotional burden of these disorders.

【 授权许可】

CC BY