Abstract
Carrier screening of Duchenne muscular dystrophy (DMD) has not been widely evaluated. To identify definite DMD female carriers prior to or in early pregnancy, we studied a large population of reproductive age females and provided informed reproductive options to DMD carriers. 37268 females were recruited from the Hangzhou Family Planning Publicity and Technology Guidance Station/Hangzhou Health Service Center for Children and Women, Hangzhou, China, between October 10, 2017, and December 16, 2018. CK activity was measured with follow-up serum DMD genetic testing in subjects with hyperCKemia, defined as CK > 200 U/L. The calculated upper reference limit (97.5th percentile) of serum creatine kinase (CK) for females aged 20-50 years in this study was near the reference limit recommended by the manufacturer (200 U/L), above which was defined as hyperCKemia. 427 females (1.2%) harbored initially elevated CK, among which 281 females (response rate of 65.8%) accepted CK retesting. DMD genetic testing was conducted on 62 subjects with sustained serum CK > 200 U/L and 16 females with a family history of DMD. Finally, 6 subjects were confirmed to be DMD definite carriers. The estimated DMD female carrier rate in this study was 1 : 4088 (adjusting for response rate), an underestimated rate, since only 50% to 70% of DMD female carriers manifest elevated serum CK, and carriers in this study may have been missed due to lack of follow-up or inability to detect all DMD pathogenic variants by current genetic testing.
Highlights
Duchenne muscular dystrophy (DMD) (MIM #310200) is a lethal degenerative neuromuscular disease, characterized by progressive muscular weakness, leading to motor delays, loss of ambulation, respiratory impairment, and cardiomyopathy, due to the loss of the protein dystrophin
A typical laboratory finding in all DMD patients, elevated plasma creatine phosphokinase (CK) concentration due to progressive muscular damage, occurs in about 50% to 70% of asymptomatic heterozygous female DMD carriers [2, 3]. This statistic was confirmed in a presurvey conducted by our group, where we recruited 32 definite DMD carriers from the Zhejiang Muscular Disease (MD) care center and found that 50% of confirmed DMD carriers had increased CK activity (Table S1)
Of the other 56 females with sustained increased serum creatine kinase but negative results of DMD genetic testing, medications and diseases such as malignancies were the most common cause of hyperCKemia. This is the first systematic and comprehensive CK screening program for DMD carriers, demonstrating the feasibility of screening asymptomatic DMD carriers through serum CK measurement combined with DMD genetic testing
Summary
Duchenne muscular dystrophy (DMD) (MIM #310200) is a lethal degenerative neuromuscular disease, characterized by progressive muscular weakness, leading to motor delays, loss of ambulation, respiratory impairment, and cardiomyopathy, due to the loss of the protein dystrophin. Becker muscular dystrophy (BMD) (MIM #300376) is similar to DMD but has a more benign phenotype due to preservation of the dystrophin reading frame. A typical laboratory finding in all DMD patients, elevated plasma creatine phosphokinase (CK) concentration due to progressive muscular damage, occurs in about 50% to 70% of asymptomatic heterozygous female DMD carriers [2, 3]. This statistic was confirmed in a presurvey conducted by our group, where we recruited 32 definite DMD carriers from the Zhejiang Muscular Disease (MD) care center and found that 50% of confirmed DMD carriers had increased CK activity (Table S1)
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