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1.
Clin Genet ; 96(3): 207-215, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31066047

RESUMO

Congenital muscular dystrophies (CMDs) are clinically and genetically heterogeneous conditions. We launched a nationwide study to determine the frequency of CMD in the Chinese population and assess the status of diagnosis and disease management for CMD in China. Cases were chosen from databases in 34 tertiary academic hospitals from 29 first-level administrative divisions (provinces, municipalities, autonomous regions, and special administrative regions), and medical records were reviewed to confirm the diagnoses. The study included 409 patients, of those patients who consented to genetic testing (n = 340), mutations were identified in 286 of them. The most common forms identified were LAMA2-related CMD (36.4%), followed by COL6-related CMD (23.2%) and α-dystroglycanopathy (21.0%). The forms of CMD related to mutations in LMNA and SEPN1 were less frequent (12.5% and 2.4%, respectively). We also recorded a significant difference in the diagnostic capabilities and disease management of CMD, with this being relatively backward in research centers from less developed regions. We provide, for the first time, comprehensive epidemiologic information of CMD in a large cohort of Chinese people. To our knowledge, this is the largest sample size of its kind so far highlighting the prevalence of CMD in China.

2.
J Obstet Gynaecol Res ; 45(6): 1096-1105, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30746853

RESUMO

AIM: Increasing preimplantation genetic testing (PGT) cycles are being performed in Hong Kong. This study aims to evaluate the knowledge, attitude and ethical consideration of Chinese couples toward PGT. METHODS: Couples requesting PGT between June 2013 and March 2014 were invited to complete a questionnaire. RESULTS: Total 49 couples (49 women, 47 men) completed the questionnaires. Eighteen couples (37%) were waiting for PGT (pre-PGT group), 15 couples (31%) were undergoing PGT (PGT group) and 16 couples (32%) had completed at least one PGT cycle (post-PGT group). Only 53% of the couples could tell the recurrent risk, and 31% (with monogenic disorders) could tell the mode of inheritance of their condition. The acceptability of PGT (>80%) and attitude toward the embryo fate (58-78%) were good. The post-PGT group had more concern than the PGT and pre-PGT groups on the prenatal diagnostic testing (**P = 0.007). 12.5% of the couples worried about the transfer of healthy embryos with carrier state and they all had monogenic disorders. If the prenatal testing confirmed an affected fetus, a higher percentage (32%) in the Post-PGT group disagreed to terminate the pregnancy in contrast to a much lower 6% in the pre-PGT group (**P = 0.02). Three-quarter of the couples opted to tell their child about their conception through PGT. CONCLUSION: Chinese couples in Hong Kong had an overall good acceptability and positive attitude toward PGT. We appreciate the difficulties the couples have gone through PGT. A checklist on what to cover pre-during-post-PGT in the counseling process is needed.

3.
Parkinsonism Relat Disord ; 63: 42-45, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30670339

RESUMO

Spinocerebellar ataxia 35 (SCA35) has been associated with pathogenic mutations in the gene TGM6. In a Chinese exome sequencing cohort, we identified 8 families with reported TGM6 variants sharing no features of SCA35. Considering this finding, we reviewed the public database gnomAD and found these variants to be significantly more common in the East Asians than in other ethnic groups (P < 0.0001). Gene constraint metrics showed that both missense and loss-of-function variants in TGM6 are likely to be tolerated and there is no regional constraint. By performing inflation analysis, it demonstrated that the cumulative frequency of TGM6 reported pathogenic variants is at least 111-fold inflated over disease prevalence of all autosomal dominant SCAs, indicating a high chance of misdiagnosis or low penetrance. Misclassification of benign or low penetrant variants as pathogenic is a significant problem that often results in genetic misdiagnosis. This highlights the necessity of evaluating variant pathogenicity with sequencing of genomes from diverse populations, both from asymptomatic controls and phenotypically different patients, in order to ensure accurate classification of variants.

4.
Neuromuscul Disord ; 27(6): 531-536, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28416349

RESUMO

Mutations in ACTA1 cause a group of myopathies with expanding clinical and histopathological heterogeneity. We describe three patients with severe ACTA1-related myopathy who have muscle fiber cytoplasmic bodies but no classic nemaline rods. Patient 1 is a five-year-old boy who presented at birth with severe weakness and respiratory failure, requiring mechanical ventilation. Whole exome sequencing identified a heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation. Patients 2 and 3 were twin boys with hypotonia, severe weakness, and respiratory insufficiency at birth requiring mechanical ventilation. Both died at 6 months of age. The same heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation was identified by whole exome sequencing. We conclude that clinically severe ACTA1-related myopathy can present with muscle morphological findings suggestive of cytoplasmic body myopathy in the absence of definite nemaline rods. The Asn94Lys mutation in skeletal muscle sarcomeric α-actin may be linked to this histological appearance. These novel ACTA1 cases also illustrate the successful application of whole exome sequencing in directly arriving at a candidate genetic diagnosis in patients with unexpected phenotypic and histologic features for a known neuromuscular gene.


Assuntos
Actinas/genética , Corpos de Inclusão/patologia , Doenças Musculares/genética , Doenças Musculares/patologia , Miopatias da Nemalina/genética , Miopatias da Nemalina/patologia , Pré-Escolar , Humanos , Masculino , Músculo Esquelético/patologia , Doenças Musculares/complicações , Mutação , Miopatias da Nemalina/complicações , Linhagem , Gêmeos , Sequenciamento Completo do Exoma
5.
J Child Neurol ; 30(2): 254-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24659733

RESUMO

We report a young boy who presented with progressive weakness of lower extremities associated with areflexia and abnormal electrophysiological findings initially suggestive of chronic inflammatory demyelinating polyneuropathy. Initial lumbosacral spinal magnetic resonance imaging (MRI) showed thickened descending spinal nerve roots only. Immunomodulating therapy was given but with limited clinical response. Repeated spine magnetic resonance imaging showed cauda equina and also new spinal cord extramedullary contrast enhancement. The initial extensive investigations including open biopsy did not point to any specific diagnosis. Only through pursuing a repeated biopsy, the diagnosis of the spinal peripheral primitive neuroectodermal tumor was confirmed. This case highlights the diagnostic challenges of the spinal peripheral primitive neuroectodermal tumor that could have an initial chronic inflammatory demyelinating polyneuropathy-like presentation. The literature review confirms that this is a rare condition and cauda equina origin has only been reported in adults and teenagers, and this is the first reported case in a young child.


Assuntos
Tumores Neuroectodérmicos Primitivos/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Criança , Progressão da Doença , Humanos , Imagem por Ressonância Magnética , Masculino , Medula Espinal/patologia , Nervos Espinhais/patologia
6.
Child Neurol Open ; 2(2): 2329048X15585345, 2015 Apr-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28503591

RESUMO

The aim of this collaborative study on Duchenne muscular dystrophy and Becker muscular dystrophy is to determine the prevalence and to develop data on such patients as a prelude to the development of registry in Hong Kong. Information on clinical and molecular findings, and patient care, was systematically collected in 2011 and 2012 from all Pediatric Neurology Units in Hong Kong. Ninety patients with dystrophinopathy were identified, and 83% has Duchenne muscular dystrophy. The overall prevalence of dystrophinopathy in Hong Kong in 2010 is 1.03 per 10 000 males aged 0 to 24 years. Among the Duchenne group, we observed a higher percentage (40.6%) of point mutations with a lower percentage (45.3%) of exon deletions in our patients when compared with overseas studies. Although we observed similar percentage of Duchenne group received scoliosis surgery, ventilation support, and cardiac treatment when compared with other countries, the percentage (25%) of steroid use is lower.

7.
Neuromuscul Disord ; 24(8): 677-83, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24957499

RESUMO

We report an eleven year old girl with early motor difficulties initially diagnosed with a peripheral neuropathy in another hospital based on abnormal electrophysiological findings. Our clinical assessment did not highlight obvious clinical features supporting a peripheral neuropathy but evidence of mild proximal weakness. Electrophysiological studies performed at our hospital revealed evidence of a sensorimotor demyelinating polyneuropathy with possible axonal involvement. Brain magnetic resonance imaging (MRI) revealed subtle white matter signal abnormalities, interpreted as nonspecific. Given the patient's proximal weakness and a mildly elevated serum creatine kinase, we performed a muscle biopsy. The muscle had mildly dystrophic features and subtly depleted laminin α2 expression. There was diffusely upregulated laminin α5 expression, and depletion of laminin α2 in intramuscular motor nerves, which made us suspect a partial laminin α2 (merosin) deficiency. Muscle MRI showed predominant posterior and medial compartments involvement. The patient was found to have autosomal recessively inherited double heterozygous LAMA2 mutations. This case illustrates the mild end of the partial merosin deficiency phenotypic spectrum, and highlights how careful assessment of laminin α2 expression in intramuscular motor nerves can be a helpful diagnostic clue in partial merosin deficiency.


Assuntos
Laminina/genética , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/genética , Biópsia , Encéfalo/patologia , Códon sem Sentido , Diagnóstico Diferencial , Feminino , Heterozigoto , Humanos , Imagem por Ressonância Magnética , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular do Cíngulo dos Membros/patologia , Distrofia Muscular do Cíngulo dos Membros/fisiopatologia , Condução Nervosa , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/fisiopatologia
8.
Pediatr Neurol ; 47(2): 137-40, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22759693

RESUMO

Congenital myasthenic syndrome caused by endplate acetylcholinesterase deficiency constitutes a rare autosomal recessive disease. We describe a child with early-onset ptosis, complete ophthalmoplegia, facial and proximal muscle weakness, easy fatigability, a decremental electromyographic response, and a repetitive compound muscle action potential not improved by anti-acetylcholinesterase medication. Mutation analysis of the collagenic tail of endplate acetylcholinesterase (COLQ) that encodes the collagenic structural subunit of acetylcholinesterase revealed two canonic splice-site mutations: a previously identified IVS15 + 1G>A mutation and a novel IVS2 - 1G>A mutation. Treatment with albuterol resulted in progressive improvement of muscle strength, exercise tolerance, and ophthalmoplegia. Further studies are needed of the efficacy of albuterol in different types of congenital myasthenic syndrome and the physiologic basis of its beneficial effects.


Assuntos
Acetilcolinesterase/deficiência , Albuterol/uso terapêutico , Síndromes Miastênicas Congênitas/tratamento farmacológico , Síndromes Miastênicas Congênitas/enzimologia , Junção Neuromuscular/enzimologia , Acetilcolinesterase/biossíntese , Acetilcolinesterase/genética , Albuterol/farmacologia , Criança , Humanos , Masculino , Síndromes Miastênicas Congênitas/diagnóstico , Junção Neuromuscular/efeitos dos fármacos , Resultado do Tratamento
9.
Pediatr Neurol ; 43(4): 274-8, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20837307

RESUMO

A young girl with antibodies to the N-methyl-D-aspartate receptor presented with a clinical syndrome suggestive of dyskinetic encephalitis lethargica with neuropsychiatric features at presentation, movement disorder, mutism, sleep disorder, and seizures. Persistent lesions in the white matter and pons were observed in magnetic resonance imaging of the brain, findings that have not been described previously in N-methyl-D-aspartate receptor antibody encephalitis.


Assuntos
Autoanticorpos/imunologia , Encéfalo/imunologia , Encefalite/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Encéfalo/patologia , Pré-Escolar , Eletroencefalografia , Encefalite/patologia , Feminino , Humanos , Imagem por Ressonância Magnética , Convulsões/imunologia , Convulsões/patologia
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