A Chinese contribution to the debate on neonatal screening methods in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is one of the most common neuromuscular disorders. In children, it causes progressive muscular deficit with cardiorespiratory complications leading to premature death. Screening at birth is often a topical issue, particularly due to the increasing number of advanced therapies (based on antisense oligonucleotides or gene therapy products) starting to emerge. The method used for this purpose involves assay of creatine phosphokinase (CPK), although this is not the only method. Detection of DMD gene abnormalities using a molecular biology approach is now envisaged.

Chinese clinical practitioners report their experience on this subject in an article published in May 2021. A study was conducted in all neonates attending the neonatal unit in one of the largest hospitals in Shanghai between 2016 and 2020. Their DNA was stored, then subsequently subjected to exhaustive analysis in 2020, as part of a new-generation sequencing (NGS) programme. Nineteen neonates out of the 10,481 tested presented a DMD gene abnormality, including 13 deletions, 4 duplications and 2 nonsense mutations. The associated phenotypes were predominantly Duchenne (n=8), Becker (n=4), and intermediate (n=5).

The authors report that follow-up protocol and genetic counselling were set in place. However interesting it may be, notably from a bioinformatics perspective (very few NGS studies have been conducted on such a scale), this study nonetheless gave rise to a number of methodological issues, starting with the enrolment bias for tested patients. The normal CPK level observed in several patients also raises questions and allows some uncertainty to remain as to the interpretation of the pathogenicity of certain DMD variants.


Genetic identification of pathogenic variations of the DMD gene: a retrospective study from 10,481 neonatal patients based on next-generation sequencing data. Xiao T, Wu B, Cao Y et al. Ann Transl Med. 2021 (Mai). 9(9):766.