肢带型肌营养不良症2D型一家系临床表型及基因突变分析

Limb-girdle muscular dystrophy type 2D:clinical and genetic analysis of a family

目的总结肢带型肌营养不良症2D型(LGMD2D型)临床表型和基因突变特点。方法报道一家系2例女性LGMD2D型患儿临床表现、肌电图、肌肉MRI、肌肉病理学和基因检测结果,并结合相关文献进行分析。结果先证者及其妹均于3岁发病,以进行性四肢近端无力为主要临床表现;血清肌酸激酶水平显著升高;肌电图呈肌源性损害;肌肉MRI显示部分肌肉萎缩、脂肪化或纤维水肿;其妹肌肉病理学显示局灶性骨骼肌坏死、再生,部分横纹肌消失,肌纤维大小不等。基因检测显示,先证者及其妹存在相同基因突变,即SGCA基因第3外显子移码突变c.262del T(p.Phe88SerfsX123)和第5外显子错义突变c.409G>A(p.Glu137Lys),其母为SGCA基因c.409G>A(p.Glu137Lys)突变携带者,其中,c.409G>A(p.Glu137Lys)为已知突变,c.262del T(p.Phe88SerfxX123)为新发突变。结论对于临床类似Duchenne型肌营养不良症的女性患者,排除DMD基因携带者后,还应行家系分析和肢带型肌营养不良症相关基因检测,以明确具体亚型。

Objective To study the characteristics and diagnosis of limb.girdle muscular dystrophy type 2D（LGMD2D）.Methods The clinical characteristics,EMG,muscle MRI and muscle pathological studies of 2 female patients in a family with LGMD2D were analyzed.Genetic analysis was used in the diagnosis of this disease.The cases were reported along with related literatures review.Results The onset of the proband and her younger sister occurred at 3 years old with progressive proximal muscle weakness of four limbs as the main clinical manifestation.The serum creatine kinase（CK） was significantly high（ 50×10^3 U/L）.EMG showed myogenic damage.Muscle MRI indicated partial muscle atrophy,fatness or fiber edema.Muscle pathological examination of the proband＇s younger sister revealed skeletal muscle necrosis and focal regeneration,partial striated muscle disappearance,and the muscle fibers in different sizes.Sequencing of all 10 coding exons of the SGCA gene in 2 patients revealed the same mutation： a c.262delT（p.Phe88SerfsX123） frameshift mutation in exon 3 and a c.409GA（p.Glu137Lys）missense mutation in exon 5.Their mother was a carrier of SGCA gene c.409GA（p.Glu137Lys） mutation.c.409GA（p.Glu137Lys） is a mutation already found,and c.262delT（p.Phe88SerfsX123） is a novel mutation.The proband＇s father did not take the genetic test for some reason.Conclusions In case of a female with Duchenne muscular dystrophy（DMD）.like symptom,if she has been excluded from the DMD gene carrier,pedigree analysis and genetic analysis involving limb.girdle muscular dystrophy（LGMD）should be conducted to facilitate the diagnosis of the LGMD and its subtypes.