Long-read Nanopore sequencing identified D4Z4 contractions in patients with facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic muscle disorder caused by abnormal expression of the DUX4 protein, commonly resulting from a contraction of D4Z4 repeat units with the presence of a polyadenylation (polyA) signal. More than 10 units of the D4Z4 repeat, with a length of 3.3 kb per unit, are typically required to silence DUX4 expression. Consequently, molecular diagnosis of FSHD is challenging. We used Oxford Nanopore technology to perform whole-genome sequencing of seven unrelated patients with FSHD, their six unaffected parents, and 10 unaffected controls. All seven patients were successfully identified to harbor one to five D4Z4 repeat units and the polyA signal, whereas none of the 16 unaffected individuals met the molecular diagnostic criteria. Our newly developed method provides a straightforward and powerful molecular diagnostic tool for FSHD.

Epidemiology and burden of Haemophilus influenzae disease in Thai children before implementation of the routine immunisation programme: A National Health Data Analysis.

OBJECTIVES: To conduct the first pre-Haemophilus influenzae (Hi) type b (Hib) immunisation programme-based epidemiological study using national health data. METHODS: We analysed National Health Security Office data, which cover 72% of the Thai population. The study population included children aged <18 years admitted for Hi disease from 2015 to 2019. Hi disease diagnosis and death were based on the International Statistical Classification of Diseases and Related Health Problems (10th revision) hospital discharge summary codes. We estimated the hospital cost per admission using diagnosis-related grouping with a global budget. RESULTS: A total of 1125 children aged <18 years were admitted for Hi disease. During the 5-year-study, the annual incidence of Hi disease varied from 1.5 to 1.9 per 100,000 children, with an overall case fatality rate (CFR) of 2%. Pneumonia was the most common clinical form, followed by meningitis and sepsis. The incidence, clinical forms and severity of Hi disease were age specific. Infant CFR was higher than that of other age groups. The incidence of Hi disease in children aged <5 years was 4.9 per 100,000 (CFR = 2.0%). Sepsis was the primary cause of infant death, whereas pneumonia was the cause of death in children aged >5 years. The hospital cost ranged from 25,000 to 30,000 THB per admission. CONCLUSIONS: This analysis provided epidemiological data of Hi in Thai children before the Hib routine immunisation programme. The incidence of Hi disease was lower than that previously speculated. Our results could facilitate an assessment of the impact of Hib immunisation programme in Thailand.

Localizing and Lateralizing Value of Seizure Onset Pattern on Surface EEG in FCD Type II.

BACKGROUND: Surface ictal electroencephalographic (EEG) monitoring has an important role in the presurgical evaluation of patients with focal cortical dysplasia (FCD). This study aimed to examine the characteristics of seizure onset pattern (SOP) on surface ictal EEG. This information will be useful for invasive monitoring planning. METHODS: We reviewed 290 seizures from 31 patients with intractable seizures related to FCD type II (6 patients with FCD IIa and 25 patients with FCD IIb). We categorized the SOPs into five patterns and evaluated the relationships between the SOPs and the location and pathology of the FCD II subtype. RESULTS: The most common SOP was no apparent change (39.0%), followed by rhythmic slow wave and repetitive spikes/sharp waves. The SOP of rhythmic slow wave was associated with FCD II in the temporal lobe (P < 0.001), and the SOP of no apparent change was associated with FCD II in the occipital lobe (P = 0.012). The SOPs of rhythmic slow waves and fast activity were most common in FCD IIa, P < 0.001 and 0.031, respectively. The repetitive spikes/sharp waves SOP was the most common pattern in FCD IIb (P < 0.001). The surface SOPs provided correct localization and lateralization of epileptic foci in FCD in 62.1% and 62.7%, respectively. In 61.3% of the patients, over 50% of the SOPs in each patient indicated accurate localization. CONCLUSIONS: SOPs in surface EEG monitoring are beneficial for presurgical evaluation and lead to localization of epileptic foci and pathologic subtypes of FCD.