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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.

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BackgroundJuvenile amyotrophic lateral sclerosis (JALS) is a rare form of motor neuron disease and occurs before 25 years of age. Only a few cases of juvenile-onset ALS have been reported.Material/MethodsTo study genetic and clinicopathological features in Chinese patients with juvenile ALS, we retrospectively reviewed ALS patients in our hospital and screened out 2 patients with disease onset before the age of 25. Genetic analysis was carried out with next-generation sequencing (NGS) to identify ALS causative genes. Sanger sequencing was used to validate identified variants. The clinical, electrophysiological, and pathological data were summarized.ResultsA novel frameshift mutation c.1510dupG (p.G505Wfs*12) was found in Patient One using next-generation sequencing (NGS). Patient Two had a reported pathogenic mutation c.C1483T(p.R495X) with NGS. The mother of Patient Two carried the same mutation as her son and disease onset was at 1.5 years after the death of her son.ConclusionsWe identified a novel frameshift mutation associated with JALS. JALS and generally typical ALS, with the same FUS mutation, can appear in a family and present a phenomenon of anticipation. For diagnosis of central nervous system degeneration in adolescents with bulbar symptoms, great attention should be paid to JALS.

Introduction: Valosin-containing protein (VCP) variants that affect muscle, bone, and the nervous system are termed multisystem proteinopathy. VCP myopathy is manifested as limb-girdle weakness, distal weakness and scapuloperoneal weakness. Methods: We reviewed clinical, genetic, and muscle biopsy data from 6 members of a family with VCP myopathy. Results: Clinical features of family members were complex and included dementia, myopathy, and hearing impairment. Ophthalmoplegia, ptosis, and dysphagia were present in 3 siblings. Rimmed vacuoles were observed in muscle biopsies, consistent with the pathological changes of VCP myopathy. A heterozygous VCP c.463C>A (p.R155S) that segregated in an autosomaldominant pattern was identified by genetic analysis. Conclusions: VCP myopathy can cause unusual manifestations that include ophthalmoplegia, ptosis, and dysphagia. This study increased our understanding of the clinical manifestations of VCP myopathy.Muscle Nerve 59: [365][366][367][368][369] 2019 Additional supporting information may be found in the online version of this article.