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1.
Clin Genet ; 106(5): 644-649, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39015008

RESUMO

Limb-girdle muscular dystrophy type 2G/R7 (LGMD2G/R7) is an ultra-rare condition initially identified within the Brazilian population. We aimed to expand clinical and genetic information about this disease, including its worldwide distribution. A multicenter historical cohort study was performed at 13 centers in Brazil in which data from index cases and their affected relatives from consecutive families with LGMD2G/R7 were reviewed from July 2017 to August 2023. Additionally, a systematic literature review was conducted to identify case reports and series of the disease worldwide. Forty-one LGMD2G/R7 cases were described in the Brazilian cohort, being all subjects homozygous for the c.157C>T/(p.Gln53*) variant in TCAP. Survival curves showed that the median disease duration before individuals required walking aids was 21 years. Notably, women exhibited a slower disease progression, requiring walking aids 13 years later than men. LGMD2G/R7 was frequently reported not only in Brazil but also in China and Bulgaria, with 119 cases identified globally, with possible founder effects in the Brazilian, Eastern European, and Asian populations. These findings are pivotal in raising awareness of LGMD2G/R7, understanding its progression, and identifying potential modifiers. This can significantly contribute to the development of future natural history studies and clinical trials for this disease.


Assuntos
Distrofia Muscular do Cíngulo dos Membros , Mutação , Humanos , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/epidemiologia , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Masculino , Brasil/epidemiologia , Feminino , Adulto , Adolescente , Pessoa de Meia-Idade , Criança , Estudos de Coortes , Adulto Jovem , Linhagem , Conectina/genética , Fenótipo , Predisposição Genética para Doença , Pré-Escolar
2.
Clin Genet ; 96(4): 341-353, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31268554

RESUMO

Limb-girdle muscular dystrophies (LGMD) are a group of genetically heterogeneous disorders characterized by predominantly proximal muscle weakness. We aimed to characterize epidemiological, clinical and molecular data of patients with autosomal recessive LGMD2/LGMD-R in Brazil. A multicenter historical cohort study was performed at 13 centers, in which index cases and their affected relatives' data from consecutive families with genetic or pathological diagnosis of LGMD2/LGMD-R were reviewed from July 2017 to August 2018. Survival curves to major handicap for LGMD2A/LGMD-R1-calpain3-related, LGMD2B/LGMD-R2-dysferlin-related and sarcoglycanopathies were built and progressions according to sex and genotype were estimated. In 370 patients (305 families) with LGMD2/LGMD-R, most frequent subtypes were LGMD2A/LGMD-R1-calpain3-related and LGMD2B/LGMD-R2-dysferlin-related, each representing around 30% of families. Sarcoglycanopathies were the most frequent childhood-onset subtype, representing 21% of families. Five percent of families had LGMD2G/LGMD-R7-telethonin-related, an ultra-rare subtype worldwide. Females with LGMD2B/LGMD-R2-dysferlin-related had less severe progression to handicap than males and LGMD2A/LGMD-R1-calpain3-related patients with truncating variants had earlier disease onset and more severe progression to handicap than patients without truncating variants. We have provided paramount epidemiological data of LGMD2/LGMD-R in Brazil that might help on differential diagnosis, better patient care and guiding future collaborative clinical trials and natural history studies in the field.


Assuntos
Genes Recessivos , Estudos de Associação Genética , Predisposição Genética para Doença , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/genética , Idade de Início , Alelos , Biomarcadores , Brasil , Progressão da Doença , Feminino , Frequência do Gene , Estudos de Associação Genética/métodos , Genótipo , Geografia Médica , Humanos , Masculino , Debilidade Muscular , Distrofia Muscular do Cíngulo dos Membros/epidemiologia , Fenótipo , Fatores Sexuais
3.
Ann Clin Transl Neurol ; 6(7): 1225-1238, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31353849

RESUMO

OBJECTIVE: ANO5-related myopathy is an important cause of limb-girdle muscular dystrophy (LGMD) and hyperCKemia. The main descriptions have emerged from European cohorts, and the burden of the disease worldwide is unclear. We provide a detailed characterization of a large Brazilian cohort of ANO5 patients. METHODS: A national cross-sectional study was conducted to describe clinical, histopathological, radiological, and molecular features of patients carrying recessive variants in ANO5. Correlation of clinical and genetic characteristics with different phenotypes was studied. RESULTS: Thirty-seven patients from 34 nonrelated families with recessive mutations of ANO5 were identified. The most common phenotype was LGMD, observed in 25 (67.5%) patients, followed by pseudometabolic presentation in 7 (18.9%) patients, isolated asymptomatic hyperCKemia in 4 (10.8%) patients, and distal myopathy in a single patient. Nine patients presented axial involvement, including one patient with isolated axial weakness. The most affected muscles according to MRI were the semimembranosus and gastrocnemius, but paraspinal and abdominal muscles, when studied, were involved in most patients. Fourteen variants in ANO5 were identified, and the c.191dupA was present in 19 (56%) families. Sex, years of disease, and the presence of loss-of-function variants were not associated with specific phenotypes. INTERPRETATION: We present the largest series of anoctaminopathy outside Europe. The most common European founder mutation c.191dupA was very frequent in our population. Gender, disease duration, and genotype did not determine the phenotype.


Assuntos
Anoctaminas/genética , Doenças Musculares/patologia , Adolescente , Adulto , Idoso , Brasil , Criança , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Doenças Musculares/diagnóstico por imagem , Distrofia Muscular do Cíngulo dos Membros , Mutação , Fenótipo , Adulto Jovem
4.
J Clin Neurophysiol ; 33(6): 554-559, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27258600

RESUMO

PURPOSE: To assess the accuracy of an unusual test for CTS investigation and correlate it with clinical symptoms. METHODS: Initially, we applied a visual analog scale for CTS discomfort (CTS-VAS) and performed a standard electrophysiologic test for CTS diagnosis (median-ulnar velocity comparison). Posteriorly, a blinded neurophysiologist performed the orthodromic simultaneous median-radial nerve stimulation (SMRS) at the thumb, with recording of both action potentials over the lateral aspect of the wrist. RESULTS: All hands (106) showed median-radial action potential splitting using the SMRS technique, in which was possible to measure the interpeak latencies (IPLs) between action potentials. The IPL and median nerve conduction velocity were different according to CTS intensity (Bonferroni; P < 0.001). There was significant correlation between IPL and median nerve conduction velocity (Spearman; r = -0.51; P < 0.01). In the same way, there was a significant correlation between IPL and median nerve conduction velocity with CTS-VAS (r = 0.6 and r = -0.3, respectively). The duration and unpleasantness of the SMRS procedure were lower when compared with standard approach (t Student < 0.001 for both comparisons). Twenty-nine symptomatic patients (39 hands) who did not fulfill criteria for CTS based on standard approach showed abnormal IPLs. CONCLUSIONS: The SMRS technique is a simple, sensitive, and tolerable approach for CTS diagnosis. Apart from that, the data from SMRS correlated better with clinical impact of CTS in comparison with the standard approach. Therefore, this method might be useful as adjunct to standard electrophysiologic approaches in clinical practice.


Assuntos
Síndrome do Túnel Carpal/terapia , Terapia por Estimulação Elétrica/métodos , Nervo Mediano/fisiologia , Nervo Radial/fisiologia , Adulto , Idoso , Síndrome do Túnel Carpal/diagnóstico , Síndrome do Túnel Carpal/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Tempo de Reação/fisiologia , Índice de Gravidade de Doença , Estatística como Assunto
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