PDF(Pubmed)
Abstract：
We report the case of a 31-year-old Chinese woman with a chief complaint of weakness in the lower limbs, which was diagnosed as limb-girdle muscular dystrophy 2B (LGMD2B) with compound heterozygous mutations of the DYSF gene. Meanwhile, this woman is an asymptomatic carrier with the mutation of the X-linked DMD gene. The electromyography, muscle MRI, and muscle biopsy indicated a chronic myogenic injury with dysferlin deletion. As a result of genetic testing, compound heterozygous G-to-T base substitution at position 5,497 in exon 49 of the DYSF gene, leading to a codon change from glutamic acid to termination codon at position 1,833, and a heterozygous C-to-G base change at position 4,638 + 8 in intron 42 of the DYSF gene with a consequence of splice, which has never been reported, were identified as candidate causative mutations. Unfortunately, DMD gene mutation c.3921+12A>G of the DMD gene on the X chromosome was also found in this patient. Finally, the patient was diagnosed as LGMD2B clinically and genetically. In the previous 2 years, the patient\'s lower limb weakness became slightly worse, resulting in even the total distance walked than before. Fortunately, during the follow-up, her son had not shown slowness or limitation of movement. Genetic testing by next-generation sequencing confirmed the final diagnosis of LGMD2B, and we identified the novel compound heterozygous variants in the DYSF gene, which is of great significance to the accurate diagnosis of genetically coded diseases. Much attention needs to be paid in clinics toward hereditary neuromuscular diseases with multiple pathogenic gene mutations. Genetic counseling and clinical follow-up should be the priorities in future, and promising treatments are also worth exploring.
摘要：
我们报道了一例31岁的中国妇女，主要主诉下肢无力，被诊断为肢体带型肌营养不良2B（LGMD2B），具有DYSF基因的复合杂合突变。同时,该女性是X连锁DMD基因突变的无症状携带者。肌电图,肌肉MRI，肌肉活检提示慢性肌源性损伤伴dysferlin缺失。作为基因检测的结果,DYSF基因外显子49第5,497位的复合杂合G-to-T碱基置换，导致在DYSF基因内含子42的第1,833位从谷氨酸到终止密码子的密码子变化，以及在第4,638+8位的杂合C-G碱基变化，从未被报道过，被鉴定为候选致病突变。不幸的是,在该患者中还发现了X染色体上DMD基因的DMD基因突变c.3921+12A>G。最后,患者在临床和遗传上被诊断为LGMD2B.在过去的两年里，病人的下肢无力变得稍微严重，导致步行的总距离比以前更远。幸运的是,在后续行动中,她的儿子没有表现出行动缓慢或受限。通过下一代测序进行的基因检测证实了LGMD2B的最终诊断，我们在DYSF基因中鉴定了新的复合杂合变体，对基因编码疾病的准确诊断具有重要意义。对于具有多个致病基因突变的遗传性神经肌肉疾病，临床上需要给予高度重视。遗传咨询和临床随访应该是未来的重点，有希望的治疗方法也值得探索。
