title: MYH7 gene tail mutation causing myopathic profiles beyond Laing distal myopathy.
abstract: OBJECTIVE
  To describe a wide range of clinical and pathologic myopathic profiles associated with the p.K1729del mutation in the MYH7 gene, known to cause Laing distal myopathy.
  
  
  METHODS
  A study conducted in the Safor region (Spain), setting of a large cluster of patients. Clinical, neurophysiologic, muscle imaging, and muscle biopsy studies and MYH7 gene sequencing were investigated in 32 patients from 4 kindreds. Data from 36 deceased or nonexamined patients were collected from hospital records or relatives.
  
  
  RESULTS
  Onset ranged from congenital to the 6th decade. All patients presented weakness of great toe/ankle dorsiflexors and many had associated neck flexor, finger extensor, and mild facial weakness. In most cases, involvement of proximal and axial muscles was observed either clinically or by muscle imaging, sometimes giving rise to scapuloperoneal and limb-girdle syndromes. Disabling myalgias, skeletal deformities, and dilated cardiomyopathy in one patient were associated features. Life expectancy was not reduced but the spectrum of disability ranged from asymptomatic to wheelchair confined. Electromyographic neurogenic features were frequently recorded. Muscle fiber type disproportion, core/minicore lesions, and mitochondrial abnormalities were the most relevant pathologic alterations. All patients carried the p.K1729del mutation in MYH7.
  
  
  CONCLUSIONS
  The p.K1729del mutation in the MYH7 gene expresses notable clinical variability and electromyographic and pathologic features that can lead to the misdiagnosis of neurogenic atrophies, congenital myopathies, or mitochondrial myopathies. Mutations in genes encoding other sarcomeric and reticulo-sarcoplasmic proteins involved in calcium regulation share pathologic characteristics with our patients, suggesting a possible pathogenetic connection.
authors: Department of Neurology, Hospital Universitario La Fe, Avda. Campanar 21, 46009 Valencia, Spain.
authors: N
authors: N
authors: Muelas
authors: P
authors: P
authors: Hackman
authors: H
authors: H
authors: Luque
authors: M
authors: M
authors: Garcés-Sánchez
authors: I
authors: I
authors: Azorín
authors: T
authors: T
authors: Suominen
authors: T
authors: T
authors: Sevilla
authors: F
authors: F
authors: Mayordomo
authors: L
authors: L
authors: Gómez
authors: P
authors: P
authors: Martí
authors: J
authors: J
authors: María Millán
authors: B
authors: B
authors: Udd
authors: J J
authors: JJ
authors: Vílchez
mesh_terms: D000293:Adolescent; D000328:Adult; D024722:Cardiac Myosins / Q000172:deficiency / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D049310:Distal Myopathies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D018995:Myosin Heavy Chains / Q000172:deficiency / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C501641:MYH7 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains