Twenty-year clinical progression of dysferlinopathy in patients from Dagestan

© 2017 Umakhanova, Bardakov, Mavlikeev, Chernova, Magomedova, Akhmedova, Yakovlev, Dalgatov, Fedotov, Isaev and Deev.To date, over 30 genes with mutations causing limb-girdle muscle dystrophy have been described. Dysferlinopathies are a form of limb-girdle muscle dystrophy type 2B with an incidence ranging from 1:1,300 to 1:200,000 in different populations. In 1996, Dr. S. N. Illarioshkin described a family from the Botlikhsky district of Dagestan, where limb-girdle muscle dystrophy type 2B and Miyoshi myopathy were diagnosed in 12 members from three generations of a large Avar family. In 2000, a previously undescribed mutation in the DYSF gene (c.TG573/574AT; p. Val67Asp) was detected in the affected members of this family. Twenty years later, in this work, we re-examine five known and seven newly affected family members previously diagnosed with dysferlinopathy. We observed disease progression in family members who were previously diagnosed and noted obvious clinical polymorphism of the disease. A typical clinical case is provided

Corrigendum: Twenty-year clinical progression of dysferlinopathy in patients from Dagestan [Front Neurol, 8, (2017) (77)] doi: 10.3389/fneur.2017.00077

The "Funding" section should be: This work was funded by Human Stem Cells Institute PJSC and Roman V. Deev. Theoretical part of this work was supported by Russian Scientific Foundation grant (14-15-00916). Ivan A. Yakovlev and Mikhail O. Mavlikeev were supported by the Russian Government Program of Competitive Growth of Kazan Federal University. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way

Effects of autologous gingiva-derived cells with myogenic potential on regeneration of skeletal muscle

In our recent studies we found for the first time the ability of human multipotent mesenchymal stromal cells (MSCs) derived from alveolar gingiva (alveolar mucosa) to differentiate into myogenic direction. The aim of the present study was to evaluate the effects of autologous gingiva-derived MSCs with myogenic potential on the regeneration of muscular tissue after mechanical damage. The study was conducted on 11 male rabbits. Biopsy of alveolar gingiva was performed at each animal before experiment for autologous MSCs obtainment. Cultures of MSCs were induced in vitro into myogenic direction. To model the damage, the medial heads of the gastrocnemius muscles were intersected on both pelvic limbs of the rabbit. Injection of autologous MSCs was performed on the seventh day after injury into the damaged muscle of one of the extremities, while equal volume of saline (control) was injected into the muscle of the contralateral limb. The animals were sacrificed on 0, 21, and 35 days after the administration of cells. MSCs transplantation led to significant reduction of the area of muscle damage. Immunohistochemical analysis revealed earlier increase in the proportion of MyoD- and myogenin-positive cells, as well as decrease in the expression of Ki-67 in damaged tissue, in experimental group compared to the control. Autologous cells did not significantly affect the composition of muscle fibers. Significant decrease in the proportion of fibrous tissue was also observed in the experimental group. The results indicate the effectiveness of autologous alveolar gingiva-derived MSCs for treatment of mechanical damage of muscle tissue. Local administration of cells accelerated reparative regeneration and prevented fibrosis

The clinical case of limb-girdle muscle dystrophy 2Q associated with myasthenic syndrome and lung damage

Limb-girdle muscle dystrophy 2Q is one of the rarest forms of plectinopathies and is represented by an isolated muscular dystrophic syndrome, according to two previously described literature reports. There are five forms of plectinopathies, including limb-girdle muscle dystrophy 2Q, are caused by mutations in the PLEC gene, the alternative splicing of which determines the synthesis of 9 isoforms of the plectin protein (1, 1a, 1b, 1c, 1d, 1e, 1f, 1g, 3) performing cytolinker function in the neuronal, epithelial and muscle tissue.The article describes the family observation of three sick siblings with the limb-girdle muscle dystrophy 2Q phenotype due to the presence of a new homozygous mutation (NM_201378.3:c.58G>T, NP_958780.1:p.Glu20Ter) in the isoform 1f PLEC revealed by whole-exome sequencing. Clinical, electromyography, visualization and histopathological features of limb-girdle muscle dystrophy 2Q were analyzed in detail. The onset of clinical manifestations in all the described siblings was observed in early childhood with moderate weakness mainly in the pelvic girdle muscles and proximal lower limbs with minimal involvement of the muscles of the shoulder girdle. A distinctive aspect is the stagnation of the myodystrophic process until 20—21 years, followed by the progression and development of episodes of respiratory failure, as well as the formation of rigidity of the cervical, thoracic spine and moderate contracture of the Achilles tendons. Typical features are marked atrophy of paravertebral muscles with the formation of pterygoid scapula and the presence of hypertrophy m. gastrocnemius, m. quadriceps femoris, m. deltoideus and m. triceps brachii. Histopathological examination m. vastus lateralis revealed myodystrophic process without inflammatory infiltration, muscle fiber cytoskeleton disorganization resulted from the plectin loss.Electrocardiography signs of the early repolarization syndrome, focal cardiosclerosis and sinus tachycardia are described. For the first time, involvement in the pathological process of pulmonary tissue in the form of noninfectious bronchiolitis, atelectasis, and the development of the myasthenic syndrome causing episodes of respiratory failure resulted in the death of two described siblings aged 29 and 31 years. Discussed pathogenetic role of PLEC 1f isoform in the development of described syndromes, expands understanding of rare nosology limb-girdle muscle dystrophy 2Q

Клинический случай поясно-конечностной мышечной дистрофии 2Q, ассоциированной с миастеническим синдромом и поражением легких

Limb-girdle muscle dystrophy 2Q is one of the rarest forms of plectinopathies and is represented by an isolated muscular dystrophic syndrome, according to two previously described literature reports. There are five forms of plectinopathies, including limb-girdle muscle dystrophy 2Q, are caused by mutations in the PLEC gene, the alternative splicing of which determines the synthesis of 9 isoforms of the plectin protein (1, 1a, 1b, 1c, 1d, 1e, 1f, 1g, 3) performing cytolinker function in the neuronal, epithelial and muscle tissue.The article describes the family observation of three sick siblings with the limb-girdle muscle dystrophy 2Q phenotype due to the presence of a new homozygous mutation (NM_201378.3:c.58G>T, NP_958780.1:p.Glu20Ter) in the isoform 1f PLEC revealed by whole-exome sequencing. Clinical, electromyography, visualization and histopathological features of limb-girdle muscle dystrophy 2Q were analyzed in detail. The onset of clinical manifestations in all the described siblings was observed in early childhood with moderate weakness mainly in the pelvic girdle muscles and proximal lower limbs with minimal involvement of the muscles of the shoulder girdle. A distinctive aspect is the stagnation of the myodystrophic process until 20—21 years, followed by the progression and development of episodes of respiratory failure, as well as the formation of rigidity of the cervical, thoracic spine and moderate contracture of the Achilles tendons. Typical features are marked atrophy of paravertebral muscles with the formation of pterygoid scapula and the presence of hypertrophy m. gastrocnemius, m. quadriceps femoris, m. deltoideus and m. triceps brachii. Histopathological examination m. vastus lateralis revealed myodystrophic process without inflammatory infiltration, muscle fiber cytoskeleton disorganization resulted from the plectin loss.Electrocardiography signs of the early repolarization syndrome, focal cardiosclerosis and sinus tachycardia are described. For the first time, involvement in the pathological process of pulmonary tissue in the form of noninfectious bronchiolitis, atelectasis, and the development of the myasthenic syndrome causing episodes of respiratory failure resulted in the death of two described siblings aged 29 and 31 years. Discussed pathogenetic role of PLEC 1f isoform in the development of described syndromes, expands understanding of rare nosology limb-girdle muscle dystrophy 2Q.Поясно-конечностная мышечная дистрофия 2Q является одной из наиболее редких форм плектинопатий и проявляется изолированным мышечным дистрофическим синдромом согласно двум ранее представленным в литературе описаниям. Пять существующих форм плектинопатий, в том числе поясно-конечностная мышечная дистрофия 2Q, обусловлены мутациями в гене PLEC, альтернативный сплайсинг которого определяет синтез 9 изоформ белка плектина (1, 1а, 1b, 1c, 1d, 1е, 1f,1g, 3), выполняющих цитолинкерную функцию в нейрональной, эпителиальной и мышечной тканях.В статье представлено описание семейного наблюдения 3 больных сибсов с поясно-конечностной мышечной дистрофией 2Q, обусловленного наличием новой гомозиготной мутации (NM_201378.3:c.58G>T, NP_958780.1:p.Glu20Ter) в изоформе 1f гена PLEC, выявленной с помощью полноэкзомного секвенирования. Детально проанализированы клинические, электронейромиографические, визуализационные и патогистологические особенности поясно-конечностной мышечной дистрофии 2Q. Дебют клинических проявлений у всех описанных членов семьи наблюдался в раннем детском возрасте в виде умеренной слабости преимущественно мышц тазового пояса и проксимальных отделов ног с минимальным вовлечением мышц плечевого пояса. Отличительным аспектом является стагнация миодистрофического процесса до 20—21 года с последующим прогрессированием и развитием эпизодов дыхательной недостаточности, а также формированием ригидности шейного, грудного отдела позвоночника и умеренной контрактуры ахилловых сухожилий. Характерными являются выраженная атрофия mm. paravertebralis с формированием крыловидных лопаток и наличие гипертрофии m. gastrocnemius, m. quadriceps femoris, m. deltoideus и m. triceps brachii. Патогистологическое исследование m. vastus lateralis отражает наличие миодистрофического процесса без воспалительной инфильтрации, дезорганизацию цитоскелета мышечных волокон и утрату плектина. Описаны электрокардиографические признаки синдрома ранней реполяризации, очагового кардиосклероза и синусовой тахикардии. Впервые в литературе представлено сочетание пояс-но-конечностной мышечной дистрофии 2Q с поражением легких в виде неинфекционного бронхиолита, ателектазов и развитием миастенического синдрома, обусловливающими эпизоды дыхательной недостаточности и повлекшие смерть 2 описываемых сибсов в возрасте 29 и 31 года. Обсуждаемое патогенетическое значение 1f-изоформы плектина в развитии описанных синдромов позволяет расширить представление о редкой нозологии — поясно-конечностной мышечной дистрофии 2Q

Corrigendum: Twenty-year clinical progression of dysferlinopathy in patients from Dagestan [Front Neurol, 8, (2017) (77)] doi: 10.3389/fneur.2017.00077

The "Funding" section should be: This work was funded by Human Stem Cells Institute PJSC and Roman V. Deev. Theoretical part of this work was supported by Russian Scientific Foundation grant (14-15-00916). Ivan A. Yakovlev and Mikhail O. Mavlikeev were supported by the Russian Government Program of Competitive Growth of Kazan Federal University. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way

Twenty-year clinical progression of dysferlinopathy in patients from Dagestan

© 2017 Umakhanova, Bardakov, Mavlikeev, Chernova, Magomedova, Akhmedova, Yakovlev, Dalgatov, Fedotov, Isaev and Deev.To date, over 30 genes with mutations causing limb-girdle muscle dystrophy have been described. Dysferlinopathies are a form of limb-girdle muscle dystrophy type 2B with an incidence ranging from 1:1,300 to 1:200,000 in different populations. In 1996, Dr. S. N. Illarioshkin described a family from the Botlikhsky district of Dagestan, where limb-girdle muscle dystrophy type 2B and Miyoshi myopathy were diagnosed in 12 members from three generations of a large Avar family. In 2000, a previously undescribed mutation in the DYSF gene (c.TG573/574AT; p. Val67Asp) was detected in the affected members of this family. Twenty years later, in this work, we re-examine five known and seven newly affected family members previously diagnosed with dysferlinopathy. We observed disease progression in family members who were previously diagnosed and noted obvious clinical polymorphism of the disease. A typical clinical case is provided

Twenty-year clinical progression of dysferlinopathy in patients from Dagestan

© 2017 Umakhanova, Bardakov, Mavlikeev, Chernova, Magomedova, Akhmedova, Yakovlev, Dalgatov, Fedotov, Isaev and Deev.To date, over 30 genes with mutations causing limb-girdle muscle dystrophy have been described. Dysferlinopathies are a form of limb-girdle muscle dystrophy type 2B with an incidence ranging from 1:1,300 to 1:200,000 in different populations. In 1996, Dr. S. N. Illarioshkin described a family from the Botlikhsky district of Dagestan, where limb-girdle muscle dystrophy type 2B and Miyoshi myopathy were diagnosed in 12 members from three generations of a large Avar family. In 2000, a previously undescribed mutation in the DYSF gene (c.TG573/574AT; p. Val67Asp) was detected in the affected members of this family. Twenty years later, in this work, we re-examine five known and seven newly affected family members previously diagnosed with dysferlinopathy. We observed disease progression in family members who were previously diagnosed and noted obvious clinical polymorphism of the disease. A typical clinical case is provided

Corrigendum: Twenty-year clinical progression of dysferlinopathy in patients from Dagestan [Front Neurol, 8, (2017) (77)] doi: 10.3389/fneur.2017.00077

The "Funding" section should be: This work was funded by Human Stem Cells Institute PJSC and Roman V. Deev. Theoretical part of this work was supported by Russian Scientific Foundation grant (14-15-00916). Ivan A. Yakovlev and Mikhail O. Mavlikeev were supported by the Russian Government Program of Competitive Growth of Kazan Federal University. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way