Plectin, which is an expression products of the PLEC genes, is a 500 kDa protein commonly expressed in mammalian tissues and cell types. It consists of an actin-binding domain, a plakin domain, a central coiled-coil rod domain, and a plakin repeat domain. It acts as a cytolinker that binds and stabilizes membrane and cytoskeletal proteins. The current research found plectin mutations may be associated with epidermolysis bullosa simplex (EBSMD), muscle atrophy, pyloric atresia, cancer and some CNS malignancies[2]. Among these, the most common plectinassociated disorder is epidermolysis bullosa simplex (EBSMD), a rare autosomalrecessive skin blistering disorder with late onset muscular dystrophy. In addition to EBSMD, Plectin mutations cause EBSMD with a myasthenic syndrome (EBSMDMyS), EBS with pyloric atresia and EBSOgna, which affect the skin exclusively.
Our patient had no cutaneous manifestations except for the symptoms of muscular dystrophy. So we reviewed the literature and found only 4 articles with absence of skin damage in plectinassociated disorders. [3–6] In 2010, Gundesli et al [3] found LGMD2Q has been identified as a homozygous 9-bp deletion in consanguineous Turkish families who produce normal skin plectin and do not show skin pathology, and it was finally confirmed by DNA sequencing that LGMD2Q was caused by a new mutation in exon c.1_9del, exon 1 of plectin isoform 1f. Another report of an Iranian family with two affected sisters a patient showing progressive limb and ocular muscle weakness without any skin involvement. Whole Exome Sequencing (WES) led to identification of a compound heterozygous mutations c.3064C > T (p.Gln1022Ter) and c.11503G > A (p.Gly3835Ser), in PLEC gene [4].Zhong et al [5] reported one case of novel compound heterozygous mutations c.5995C > T (p.Arg1999Trp) and c.9940T > A (p.Phe3314 Ile) in the PLEC gene were identified in a Chinese family without other symptoms. In 2018, Liang et al [6] presented a patient in Taiwan, China with PLEC mutations c.12731G > A (p.Arg4244His) and c.7928A > G (p.Glu2643Gly), which onset in early childhood and slow progression. He was ambulant with neck, mild proximal muscle, and facial weakness without any skin lesions or gastrointestinal problems. Deev et al [7] also found a case of LGMD2Q due to a new homozygous mutation c.58G > T, showing progressive contracture of the Achilles tendon, with progressive weakening of muscle strength in the proximal lower limbs. Severe pulmonary lesions were seen on chest CT.
In conclusion, our case was the first pure late-onset muscular dystrophy due to novel compound heterozygous PLEC mutations. This observation extends the phenotypic spectrum of PLEC related diseases.