P.180 Diagnostic range of targeted next-generation sequencing in a single center experience with limb-girdle muscular dystrophy

Abstract

Limb-girdle muscular dystrophies (LGMDs) are clinically and genetically heterogeneous group of muscle disease characterized by proximally predominant weakness of the shoulder and hip girdle musculature. Recent advances in genetic testing have contributed to increasing diagnostic yields and better understanding each subtype of LGMDs. We investigated genetic variability and clinical manifestation among a single center study of Korean patients with LGMD. We reviewed medical records of myopathy data from January 2002 to August 2021 at Gangnam Severance Hospital. Among 1,028 patients with muscular dystrophies, we selected 334 patients with LGMD from 304 unrelated families. We investigated diagnostic rate of targeted next-generation sequencing and genotypes of 304 families with LGMD. Pathogenic/likely pathogenic variants were found in 184 (55.1%) patients out of 304 families with LGMD. Diagnostic rate of targeted next-generation sequencing in our center was 158 (52%) out of 304 families. Additionally, 16 (5.3%) families had a one heterozygous variant of recessive myopathy. <i>DYSF</i> (97 families) was the most common genetic cause in Korean patients with LGMDs, followed by <i>CAPN3</i> (25), <i>COL6A1/A2</i> (17), <i>TTN</i> (6), <i>DNAJB6</i> (4), <i>FKRP</i> (2), <i>GMPPB</i> (1), <i>LAMA2</i> (1), <i>PLEC</i> (1), <i>SGCA</i> (1), <i>SGCB</i> (1), <i>SGCG</i> (1), and <i>TNPO3</i> (1). Cases with one heterozygous variant of recessive myopathy were in <i>DYSF</i> (10 families), <i>CAPN3</i> (5), and <i>TTN</i> (1). The total 184 patients were genetically confirmed from 158 families, and comprised of 90 men and 94 women. In dysferlinopathy, we genetically verified 102 Patients from 97 families. There were 45 men and 57 women. The median age at the symptom onset and the diagnosis were 23 years [Interquartile range (IQR): 18-30 years] and 37 years [IQR: 27-47 years], respectively. In calpainopathy, 28 patients from 25 families included 18 men and 10 women. The median age at the symptom onset and the diagnosis was 18 years [IQR: 16-27 years] and 34 years [IQR: 25-45], respectively. Serum creatine kinase (CK) levels were highest in patients with dysferlinopathy. The median level of CK in dysferlinopathy was 4,871 IU/l [IQR: 2,400-8,145 IU/l]. This study showed the diagnostic rate of targeted next-generation sequencing in Korean patients with LGMD.