Expanding the clinical and genetic spectrum of pathogenic variants in STIM1.
Muscle Nerve
; 64(5): 567-575, 2021 11.
Article
en En
| MEDLINE
| ID: mdl-34368974
ABSTRACT
INTRODUCTION/AIMS:
Stromal interaction molecule 1 (STIM1) is a reticular Ca2+ sensor composed of a luminal and a cytosolic domain. Autosomal dominant mutations in STIM1 cause tubular aggregate myopathy and Stormorken syndrome or its variant York platelet syndrome. In this study we aimed to expand the features related to new variants in STIM1.METHODS:
We performed a cross-sectional study of individuals harboring monoallelic STIM1 variants recruited at five tertiary centers involved in a study of inherited myopathies analyzed with a multigene-targeted panel.RESULTS:
We identified seven individuals (age range, 26-57 years) harboring variants in STIM1, including five novel changes three located in the EF-hand domain, one in the sterile α motif (SAM) domain, and one in the cytoplasmatic region of the protein. Functional evaluation of the pathogenic variants using a heterologous expression system and measuring store-operated calcium entry demonstrated their causative role and suggested a link of new variants with the clinical phenotype. Muscle contractures, found in three individuals, showed variability in body distribution and in the number of joints involved. Three patients showed cardiac and respiratory involvement. Short stature, hyposplenism, sensorineural hearing loss, hypothyroidism, and Gilbert syndrome were variably observed among the patients. Laboratory tests revealed hyperCKemia in six patients, thrombocytopenia in two patients, and hypocalcemia in one patient. Muscle biopsy showed the presence of tubular aggregates in three patients, type I fiber atrophy in one patient, and nonspecific myopathic changes in two patients.DISCUSSION:
Our clinical, histological, and molecular data expand the genetic and clinical spectrum of STIM1-related diseases.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trastornos de las Plaquetas Sanguíneas
/
Miopatías Estructurales Congénitas
Tipo de estudio:
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Muscle Nerve
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia