Abstract:

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.409G > A (p.Glu137Lys) missense mutation in exon 5. Their mother was a carrier of SGCA gene c.409G > A (p.Glu137Lys) mutation. c.409G > A (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.

Key words: Muscular dystrophies, limb-girdle, Phenotype, Genes, Mutation, Pedigree

摘要：

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.262delT（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.262delT（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。

关键词: 肌营养不良, 肢带型, 表型, 基因, 突变, 系谱