Delineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population.

BACKGROUND: Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs. METHODS: We recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤ 1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines. RESULTS: Sixty-six patients with pre-biopsy MDC scores of 3-8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n = 3, two were siblings), ALDH5A1, ARX, FA2H, KCNT1, LDHD, NEFL, NKX2-2, TBCK, and WAC. CONCLUSIONS: We confirmed that the COQ4:c.370G>A, p.(Gly124Ser) variant, was a founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous.

Thrombotic thrombocytopenic purpura as a rare complication in childhood systemic lupus erythematosus: case report and literature review.

Thrombotic thrombocytopenic purpura is a rare but serious condition in childhood. It can be idiopathic or a complication of other diseases or drug therapy. We report on a 12-year-old Chinese girl who presented with fulminant systemic lupus erythematosus with progressive renal failure, pancytopenia, and cerebral dysfunction due to thrombotic thrombocytopenic purpura. The patient also had Pneumocystis carinii pneumonia, Pseudomonas septicaemia, and Herpes zoster infections as a result of immunosuppressive treatment. She responded to combined therapy with pulse methylprednisolone, cyclophosphamide, plasmapheresis, and intensive care support, and completely recovered renal and neurological function. A review of the English-language medical literature since 1968 identified 20 other paediatric cases of systemic lupus erythematosus and thrombotic thrombocytopenic purpura. Clinical features, treatment, and outcome of these cases are presented and discussed. Early recognition is important, and although plasmapheresis is not of proven benefit in severe cases of systemic lupus erythematosus, it is life-saving in lupus-related thrombotic thrombocytopenic purpura and must be instituted early to avoid a poor outcome.

Epidemiology of childhood epilepsy in a cohort of 309 Chinese children.

The present study describes the characteristics of epilepsy in a cohort of Chinese epileptic children. All children with active epilepsy who were under 15 years of age and residing in the catchment area of Tuen Mun Hospital, Hong Kong were monitored. Etiology, seizure types, and epilepsy syndromes were classified according to the recent guidelines of the International League Against Epilepsy. A total of 309 children were recruited into the study. The etiology of epilepsy was idiopathic in 42% of the children, cryptogenic in 16.8%, and remote symptomatic in 40.8%. Perinatal factors were the most frequently found cause of epilepsy. Seizure types were partial in 48.5% of the children and generalized in 46.9%. Epilepsy syndromes could be classified in all but seven patients, with 48.2% localization related and 49.5% generalized. Generalized seizures were more prevalent in children less than 5 years of age. Additional neuroimpairments affected 36% of our epileptic children. Sixty-nine percent of patients were seizure free for more than 1 year. The authors conclude that the International League Against Epilepsy can be applied successfully to a population-based cohort of Chinese epileptic children. A larger, longitudinal epidemiologic study is needed to answer questions concerning the true prevalence, incidence, types, and etiologies in the Chinese population.