Targeted sequencing of the DMD locus: A comprehensive diagnostic tool for all mutations

Background & objectives: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder and is caused mainly by deletion, duplication and point mutations in the DMD gene. Diagnosis of DMD has been a challenge as the mutations in the DMD gene are heterogeneous and require more than one diagnostic strategy for the validation of the mutation. This study was planned to evaluate the targeted next-generation sequencing (NGS) as a single platform to detect all types of mutations in the DMD gene, thereby reducing the time and costs compared to conventional sequential testing and also provide precise genetic information for emerging gene therapies. Methods: The study included 20 unrelated families and 22 patients from an Indian population who were screened for DMD based on phenotypes such as scoliosis, toe walking and loss of ambulation. Peripheral blood DNA was isolated and subjected to multiplex ligation-dependent probe amplification (MLPA) and targeted NGS of the DMD gene to identify the nature of the mutation. Results: In the study patients, 77 per cent of large deletion mutations and 23 per cent single-nucleotide variations (SNVs) were identified. Novel mutations were also identified along with reported deletions, point mutations and partial deletions within the exon of the DMD gene. Interpretation & conclusions: Our findings showed the importance of NGS in the routine diagnostic practice in the identification of DMD mutations over sequential testing. It may be used as a single-point diagnostic strategy irrespective of the mutation type, thereby reducing the turnaround time and cost for multiple diagnostic tests such as MLPA and Sanger sequencing. Though MLPA is a sensitive technique and is the first line of a diagnostic test, the targeted NGS of the DMD gene may have an advantage of having a single diagnostic test. A study on a larger number of patients is needed to highlight NGS as a single, comprehensive platform for the diagnosis of DMD.

A case of partial deletion of the long arm of chromosome 7 / 中南大学学报(医学版)

Partial deletion of the long arm of chromosome 7 is a rare disease and is prone to missing the diagnosis or being misdiagnosed.Here we present a case of a 13-year-old boy that showed symptoms such as growth-retardation,moderate intellectual disability,hypotelorism,microcephaly,epicanthal folds,genu varum and lumbar vertebral cleft,but it did not show serious symptoms like cleft lip,urogenital malformation and hypotonia.He was eventually diagnosed as partial deletion of the long arm of chromosome 7 syndrome through gene analysis.Considering the rare incidence of this disease and more rarely for being hospitalized to endocrine ward due to growth retardation,this case report can provide more information for clinic diagnosis and differential diagnosis for growth retardation.