Genomewide association study of leprosy.

BACKGROUND: The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS: We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS: We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS: Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae.

[Observation on therapeutic effect of filiform fire needle assisted 308 nm excimer laser on vitiligo of different parts].

OBJECTIVE: To compared the therapeutic effect between filiform fire needle assisted 308 nm excimer laser and simple 308 nm excimer laser on vitiligo of different parts. METHODS: Target lesions of 134 patients were divided into an observation group and a control group according to the principle of self-controlled, 201 pieces in each one. In the observation group, filiform fire needle was performed at target lesions. Then target lesions both of the two groups were irradiated with 308 nm excimer laser at the same time. Once every 2 weeks, totally 10 treatments were required. The effective rate and effective rate, color recovery rate and responding time of different parts in the two groups were evaluated 2 weeks after treatment. RESULTS: The effective rate in the observation group was 82.59% (166/201), which was higher than 68.16% (137/201) in the control group (P<0.01). The effective rate of face-neck, trunk, limbs and hand-foot were 90.32%, 81.63%, 81.48% and 58.62% respectively in the observation group, which were higher than 82.80%, 69.39%, 51.85% and 31.03% in the control group (P<0.01, P<0.05). The color recovery rate of different parts in the observation group was higher than the control group, and the effect was faster in the observation group (P<0.01, P<0.05). CONCLUSION: Filiform fire needle as an adjunctive therapy, combined with 308 nm excimer laser are more effective than simple 308 nm excimer laser for vitiligo of different parts. Combination therapy has a shorter responding time, the face-neck has the best effect and hand-foot has poor effect.

Identification of Seven Novel Mutations in the Acid Alpha-glucosidase Gene in Five Chinese Patients with Late-onset Pompe Disease.

BACKGROUND: Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene (GAA). A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease (LOPD) who carried novel GAA gene mutations. METHODS: Clinical and pathological data of patients diagnosed with glycogen storage disease at our institution from April 1986 to August 2017 were collected, and next-generation sequencing of frozen muscle specimens was conducted. RESULTS: Of the five patients included in the study, the median disease onset age was 13 years, with a median 5 years delay in diagnosis. The patients mainly manifested as progressive weakness in the proximal and axial muscles, while one patient developed respiratory insufficiency that required artificial ventilation. In muscle biopsies, vacuoles with variable sizes and shapes appeared inside muscle fibers, and they stained positive for both periodic acid-Schiff and acid phosphatase staining. Ten GAA gene mutations, including seven novel ones (c.796C>A, c.1057C>T, c.1201C>A, c.1780C>T, c.1799G>C, c.2051C>A, c.2235dupG), were identified by genetic tests. CONCLUSIONS: The seven novel GAA gene mutations revealed in this study broaden the genetic spectrum of LOPD and highlight the genetic heterogeneity in Chinese LOPD patients.

A Novel Mutation of Mitochondrial T14709C Causes Myoclonic Epilepsy with Ragged Red Fibers Syndrome in a Chinese Patient.

BACKGROUND: Myoclonic epilepsy with ragged red fibers (MERRF) syndrome is characterized by myoclonus, generalized epilepsy, cerebellar ataxia, and ragged red fibers (RRFs) in the muscle. T-to-C transition at nucleotide position 14709 in the mitochondrial tRNA glutamic acid (tRNAGlu) gene has previously been associated with maternally inherited diabetes and deafness. However, the association between MERRF and mitochondrial T14709C mutation (m.T14709C) has never been reported before. METHODS: Clinical information of a 17-year-old patient was collected; muscle biopsy and next-generation sequencing (NGS) of whole mitochondrial and neuromuscular disease panel were then conducted. Finally, sanger sequencing was carried out to confirm the mutations. RESULTS: The patient presented a typical MERRF phenotype with muscle weakness, epileptic seizure, clonic episodes, cerebellar ataxia, and spinal scoliosis. Muscle biopsy showed RRFs which indicated abnormal mitochondrial functions. NGS of whole mitochondrial gene revealed m.T14709C mutation, confirmed by Sanger sequencing. CONCLUSION: We present a sporadic patient with typical MERRF presentation carrying the mutation of m.T14709C, which expanded the spectrum of m.T14709C.

Oculopharyngeal Weakness, Hypophrenia, Deafness, and Impaired Vision: A Novel Autosomal Dominant Myopathy with Rimmed Vacuoles.

BACKGROUND: Myopathies with rimmed vacuoles are a heterogeneous group of muscle disorders with progressive muscle weakness and varied clinical manifestations but similar features in muscle biopsies. Here, we describe a novel autosomal dominant myopathy with rimmed vacuoles in a large family with 11 patients of three generations affected. METHODS: A clinical study including family history, obstetric, pediatric, and development history was recorded. Clinical examinations including physical examination, electromyography (EMG), serum creatine kinase (CK), bone X-rays, and brain magnetic resonance imaging (MRI) were performed in this family. Open muscle biopsies were performed on the proband and his mother. To find the causative gene, the whole-exome sequencing was carried out. RESULTS: Disease onset was from adolescence to adulthood, but the affected patients of the third generation presented an earlier onset and more severe clinical manifestations than the older generations. Clinical features were characterized as dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision. However, not every patient manifested all symptoms. Serum CK was mildly elevated and EMG indicated a myopathic pattern. Brain MRI showed cerebellum and brain stem mildly atrophy. Rimmed vacuoles and inclusion bodies were observed in muscle biopsy. The whole-exome sequencing was performed, but the causative gene has not been found. CONCLUSIONS: We reported a novel autosomal dominant myopathy with rimmed vacuoles characterized by dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision, but the causative gene has not been found and needs further study.

Assessment of knowledge and skills in early diagnosis of leprosy and attitudes towards leprosy amongst doctors working in dermatological services, Shandong Province, People's Republic of China.

After the leprosy control programme in Shandong Province, China, had declared elimination in 1994, it was no longer cost effective to rely on rapid surveys, population surveys and contact tracing for case detection, and since then most new cases have been diagnosed by the dermatological services. The dermatological services will continue to play an important role in diagnosis of the few incident leprosy cases scattered in wide geographic areas and in a population of 90 million. In order to better understand the knowledge and skills in early diagnosis of leprosy among doctors working in dermatological services around the province, doctors attending the dermatological annual meeting and a dermatological training workshop were assessed on their knowledge and skills in early diagnosis of leprosy and their attitude towards leprosy with a semi-structured questionnaire. The results showed that continuous training was needed for dermatologists from both general hospitals and the leprosy control programme. In particular, the training methods for the skills in nerve examination including palpation of peripheral nerves and nerve function assessment should be improved.

Comparison of histologic, biochemical, and mechanical properties of murine skin treated with the 1064-nm and 1320-nm Nd:YAG lasers.

The goal of this study was to compare the effects of the Q-switched 1064-nm Nd:YAG laser and the 1320-nm Nd:YAG laser non-ablative treatments on mouse skin in vivo. Skin elasticity measurements were carried out with a Reviscometer, and skin samples were taken for histological study, hydroxyproline content assay and estimation of collagen type I and III. By the second month after non-ablative treatments, the 1064-nm laser treatment resulted in an average of 25% greater improvement of skin elasticity, 6% more increase of dermal thickness, and 11% higher synthesis of hydroxyproline than the 1320-nm laser. Collagen type III increased markedly after the 1064-nm laser treatment whereas more collagen type I was elicited by the 1320-nm laser. Our results demonstrated that the 1064-nm laser was more effective than the 1320-nm Nd:YAG laser in non-ablative treatments, but the results needed to be confirmed in humans. It appeared that photo-mechanic reaction could cause more collagen type III synthesis whereas the photo-thermal effect was in favor of the formation of collagen type I.