Myofibrillar myopathies

Abstract

Purpose of review Myofibrillar myopathies (MFMs) are a heterogeneous group of skeletal and cardiac muscle diseases. In this review, we highlight recent discoveries of new genes and disease mechanisms involved in this group of disorders. Recent findings The advent of next-generation sequencing technology, laser microdissection and mass spectrometry-based proteomics has facilitated the discovery of new MFM causative genes and pathomechanisms. New mutations have also been discovered in ‘older’ genes, helping to find a classification niche for MFM-linked disorders showing variant phenotypes. Cell transfection experiments using primary cultured myoblasts and newer animal models provide insights into the pathogenesis of MFMs. Summary An increasing number of genes are involved in the causation of variant subtypes of MFM. The application of modern technologies in combination with classical histopathological and ultrastructural studies is helping to establish the molecular diagnosis and reach a better understanding of the pathogenic mechanisms of each MFM subtype, thus putting an emphasis on the development of specific means for prevention and therapy of these incapacitating and frequently fatal diseases.

Des Gene Mutation in a Family of Proband With Myofibrillary Myopathy and Non-Compaction Cardiomyopathy, Resulted in Cardiac Transplantation

“…Внимание к этой группе обусловлено ранним дебютом заболевания, низким качеством жизни из-за тяжести основного заболевания, а также неблагоприятным прогнозом за счет наличия тяжелой сердечной недостаточности, жизнеопасных нарушений ритма сердца и проводи-мости [2,5,11,12]. Миофибриллярные миопатии -гетерогенная группа нервно-мышечных заболеваний, вызванных мутациями в генах десмина (DES), αB-кристаллина (CRYAB), миотилина (MYOT), фила-мина C (FLNC), а также BAG3 и ZASP [13]. Общей патологической картиной миофибрил-лярных миопатий является растворение миофи-брилл, агрегация деградированных миофибрилляр-ных продуктов и эктопическая экспрессия белков, при этом клинические проявления при дефекте каждого из вышеперечисленных белков различны.…”

A novel dominant D109A CRYAB mutation in a family with myofibrillar myopathy affects αB-crystallin structure

“…Abnormal expression of desmin ( DES ), myotilin ( MYOT ), αB-crystallin ( CRYAB or HSPB5 ) and dystrophin ( DMD ) results in accumulation of degraded filamentous material in various patterns mostly in myofibril-free fiber regions around nuclei and under the sarcolemma. Membranous organelles are dislocated and their degradation in autophagic vacuoles can be also observed [1].…”

“…A growing number of genes have been associated with MFM pathogenesis, causing subtypes of the disease [1]. So far nine MFM-causing genes encoding Z-disc associated proteins have been identified: DES , CRYAB , MYOT , Z band alternatively spliced PDZ-containing protein ( ZASP ), filamin C ( FLNC ), Bcl2-associated athanogene-3 ( BAG3 ), four-and-a-half LIM protein-1 ( FHL1 ), titin ( TTN ) and sarcomeric actin ( ACTA1 ) ( see [5] for review).…”

Novel LDB3 Mutation in a Patient With Autosomal Dominant Myofibrillar Myopathy

“…Myofibrillar myopathies (MFM, [MIM 601419]) are a group of clinically and genetically heterogeneous neuromuscular disorders defined by ectopic expression of proteins, such as desmin, and myofibrillar disorganization starting at the Z-disk and protein aggregates in muscle fibers (1). The clinical phenotypes of myofibrillar myopathies are widely heterogeneous.…”