第七届北京罕见病学术大会暨2019京津冀罕见病学术大会征文（127）

Department of Neurology， Peking University First Hospital， Beijing， China

Ma JJ， Xie ZY， Yu M， Zheng YM， Wang ZX， Yuan Y，

The disease severity in female manifesting carriers with DMD mutation baried largely， from mild muscle weakness to DMD-like disease progression. However， the related factors to disease severity remained ambiguous. In this study， we aim to review the population-specific features of manifesting carriers， with emphasis on factors associated to worse clinical outcomes. Method: We retrospectively collected clinical， pathological and genetic records of 14 manifesting carriers. The age at disease onset varied from1 to 54 years in these manifesting carriers. Only 1 had definite family history of DMD. Manifesting carriers was defined as females with weakness or dilated cardiomyopathy. Muscle weakness would be categorized as “severe”， “moderate” or “mild”， if patient’s mMRC score was located in “0~3+”， “4-~4” or “4+~5-” respectively. Second genetic sequence for DMD gene Muscle biopsy performed with immunohistochemical studies were performed in all patients. Result: The muscle weakness was seen in 12 (86%) patients and 3 (21%) of them were in severe group. Delayed walking (≥16mo) was noted in 8 patients 60%.  Delayed walking associated significantly with severity of diseases (p＜0.01＝. Mosaic reduction of dystrophin was presented in 9 patients (69%) and total loss in the remaining 4 patients with early onset DMD like phenomenon (2/4). There were 9 exonic deletions/duplications with destructed reading-frame， 1 exonic duplication with intact reading-frame， 3 nucleotide insertions/deletions and 1 X;5 translocation had been detected. Weakness progression seemed to be slower in in-frame mutation but more aggressive in X;5 translocation. Conclusion: motor retardation， severe loss of dystrohin in muscle fiber and X;5 translocation associated with poor prognosis. The reading-frame rule could not be used for evaluation of disease outcome.