Ataxins ; Humans ; Male ; Middle Aged ; Nerve Tissue Proteins ; genetics ; Spinocerebellar Ataxias ; genetics ; Trinucleotide Repeats

Objective To investigate the clinical features and pathogenic genes of a familial hypokalemic periodic paralysis ( HOKPP).Methods PCR amplification and DNA sequencing were used to screen candidate genes of the HOKPP family members (CACNA1S, SCN4A, KCNE3), and the clinical features were carefully analyzed at the same time.Results The sequencing analyses of the SCN4A gene in the proband identified three nucleotide sequence mutations, which influenced the amino acid sequence of the skeletal sodium channel.One of the mutations was identified as a C/T heterozygous pattern at the 2111th nucleotide position in exon 13, resulting in a change from Thr to Met at the 704th amino acid position of the sodium channel protein.All affected patients carried the Thr704Met mutation, whereas unaffected family members did not.Clinical symptoms in this family followed an autosomal dominant inheritance pattern.Muscles weakness, pain and hypokalemia in the period between attacks were seen in all patients.Paralytic symptoms occurred early, lasted longer and recurred frequently, while cold was the main predisposing factor.With the progress of the disease, patients represented persistent weakness and atrophy in proximal muscles.Conclusions Mutation (Thr704Met) in the SCN4A gene should be responsible for this family.This mutation causes severe HOKPP and progressive muscle atrophy.

Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome is a rare X-linked dominant and male-lethal multi-system disorder characterized by congenital hemidysplasia, strictly lateralized ichthyosiform nevus and ipsilateral limb defects. CHILD syndrome is caused by mutations of nicotinamide adenine dinucleotide phosphate steroid dehydrogenase-like protein (NSDHL) gene mapped to chromosome Xq28. The gene encodes 3β-hydroxylsterol dehydrogenase, which catalyses a step in the cholesterol biosynthetic pathway. This paper has provided a review for recent progress in research on CHILD syndrome including its clinical aspects, pathology, etiology, pathogenesis, differential diagnosis, and treatment, with a particular emphasis on its treatment..
Abnormalities, Multiple ; genetics ; Genetic Diseases, X-Linked ; genetics ; Humans ; Limb Deformities, Congenital ; genetics ; Nevus ; genetics ; Syndrome

OBJECTIVETo analyze the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) for patients with locally advanced non-small-cell lung cancer (LA-NSCLC).

METHODSClinical data of 251 patients with stage III (76 IIIA and 175 IIIB) NSCLC who received CCRT as initial treatment between Jan 2001 and Dec 2010 in our hospital were reviewed. A median total radiotherapy dose of 60 Gy (range, 50-74 Gy) were delivered. 174 patients were treated with IMRT, 51 with 3D-CRT and 26 with 2D-radiotherapy. EP chemotherapy regimen was administered in 112 patients, PC regimen in 99 patients, topotecan regimen in 18 patients and other regimens in the remaining 22 patients. The efficacy and toxicity of CCRT were retrospectively analyzed.

RESULTS244 patients were assessable for response, including 6 (2.5%) patients with CR, 183 (75.0%) with PR, 42 (17.2%) with SD and 13 (5.3%) with PD. At a median follow-up period of 20 months, the 1-, 3-, 5- year OS were 69.2%, 31.2%, 23.2%, respectively, and the median OS was 21 months. The 1-, 3-, 5- year PFS were 40.9%, 22.1%, 17.7%, respectively, and the median PFS was 10 months. Patients with stage IIIA NSCLC achieved better 5-year OS than that with IIIB NSCLC (29.2% vs. 20.7%, χ2=2.254, P=0.133). Failure pattern was assessable in 244 patients, including 61 (25.0%) locoregional progression alone, 55 (22.5%) distant metastasis alone and 77 (31.6%) with both. The rates of grade≥3 radiation pneumonitis, esophagitis and hematologic toxicity were 4.4%, 11.2% and 26.4%, respectively.

CONCLUSIONSCCRT provide stage III NSCLC patients favorable outcome with acceptable toxicity. CCRT is standard therapeutic approach for patients with unresectable locally advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; pathology ; therapy ; Chemoradiotherapy ; Cisplatin ; administration & dosage ; Cyclophosphamide ; administration & dosage ; Esophagitis ; etiology ; Humans ; Lung Neoplasms ; pathology ; therapy ; Neoplasm Staging ; Radiation Pneumonitis ; etiology ; Radiotherapy, Conformal ; Retrospective Studies ; Topotecan ; administration & dosage