MYH7 mutation associated with two phenotypes of myopathy

Abstract

The mutations of MYH7 (slow skeletal/β-cardiac myosin heavy chain) are commonly found in familial hypertrophic/dilated cardiomyopathy, and also can cause Laing early-onset distal myopathy (LDM), myosin storage myopathy (MSM), and congenital myopathy with fiber-type disproportion (CFTD). Here we report two cases whose diagnosis was hereditary myopathy according to clinical feature and muscle pathology analysis. High-throughput genomic sequencing (next generation sequencing) was performed to validate the diagnosis. Two MYH7 mutations, p.R1845W and p.E1687del, were identified. p.R1845W was found in a male patient showing weakness of both terminal lower legs without foot drop. Muscle pathology stainings characteristically showed the hyaline body in the intracytoplasmic location. The novel mutation p.E1687del was found in a family with seven patients. The proband showed foot drop, scoliosis, and winged scapula, while his mother only showed mild foot drop and winged scapula. Muscle pathology analysis showed congenital centronucleus myopathy. Both cases only showed muscular disorder and had no cardiomyopathy. This study, for the first time, reports the MYH7 mutations associated with centronucleus myopathy.

Clinical Features and Genotypes of Laing Distal Myopathy in a Group of Chinese Patients, With In-Frame Deletions of MYH7 as Common Mutations

“…Referring to published articles on Laing distal myopathy, common mutation types also include missense mutations, and inframe indels. The p.K1617del and p.E1508del have also been reported in a few studies [5,6,8,9,12,15,19,23,24].Besides these in-frame indels in our study, other reported mutations include p.E1687del, p.K1729del, p.E1669del, p.K1729dup, p.L1793del, p.K1784del [5,9,11,16,[26][27][28]. Therefore, in-frame deletions or duplications are common types of mutations in Laing distal myopathy.…”

“…In this study, we have described a series of patients with genetic con rmed Laing distal myopathy. Up to now, there have been more than 30 articles on Laing distal myopathy, including three reports on Chinese patients [10][11][12]. So far, this is the largest report on Laing distal myopathy in China.…”

“…Up to now, a number of both sporadic and familial LDM cases have been reported around the world, including several Chinese cases [10][11][12]. Here, we report three Chines LDM pedigrees and one sporadic Chinese LDM patient, and describe the clinical, radiographical, pathological and mutational features of these cases, to further expand both the genotypes and the phenotypes of LDM.…”

Clinical features and genotypes of Laing distal myopathy in a group of Chinese patients, with in-frame deletions of MYH7 as common mutations

“…In this study, we have described a series of patients with genetic con rmed Laing distal myopathy. Up to now, there have been more than 30 articles on Laing distal myopathy, including three reports on Chinese patients [10][11][12]. So far, this is the largest report on…”

“…Up to now, a number of both sporadic and familial LDM cases have been reported around the world, including several Chinese cases [10][11][12]. Here, we report three Chines LDM pedigrees and one sporadic Chinese LDM patient, and describe the clinical, radiographical, pathological and genetic features of these cases, to further expand both the genotypes and the phenotypes of LDM.…”