GJB2: the spectrum of deafness-causing allele variants and their phenotype

Genetic testing was completed on 1,294 persons with deafness referred to the Molecular Otolaryngology Research Laboratories to establish a diagnosis of DFNB1. Exon 2 of GJB2 was screened for coding sequence allele variants by denaturing high-performance liquid chromatography (DHPLC) complemented by bidirectional sequencing. If two deafness-causing mutations of GJB2 (encoding Connexin 26) were identified, further screening was not performed. If only a single deafness-causing mutation was identified, we screened for the g.1777179_2085947del (hereafter called del(GJB6-D13S1830); GenBank NT_024524.13) and mutations in the noncoding region of GJB2. Phenotype-genotype correlations were evaluated by categorizing mutations as either protein truncating or nontruncating. A total of 205 persons carried two GJB2 exon 2 mutations and were diagnosed as having DFNB1; 100 persons carried only a single deafness-causing allele variant of exon 2. A total of 37 of these persons were c.35delG carriers, and 51 carried other allele variants of GJB2. Persons diagnosed with DFNB1 segregating two truncating/nonsense mutations had a more severe phenotype than persons carrying two missense mutations, with mean hearing impairments being 88 and 37%, respectively (P < 0.05). The number of deaf c.35delG carriers was greater than expected when compared to the c.35delG carrier frequency in normal-hearing controls (P < 0.05), suggesting the existence of at least one other mutation outside the GJB2 coding region that does not complement GJB2 deafness-causing allele variants.     

Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

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Association between age and disease specific mortality in medullary thyroid cancer

BackgroundThe aim of this study was to evaluate the association between age and disease specific mortality (DSM) among adults diagnosed with medullary thyroid cancer (MTC).MethodSurveillance, Epidemiology, and End Results (SEER-18) was used to analyze adult MTC patients stratified by age (18–64, 65–79, ≥80 years). Associations between patient demographics, tumor size, nodal status, metastatic disease, and extent of surgery on DSM was assessed with multivariable Cox regression.ResultsAmong 1457 patients with MTC, 1008 (69.2%) were younger adults, 371 (25.5%) older adults, and 78 (5.4%) were super-elderly. A significantly higher proportion of older adults and super-elderly had less than the recommended operation for MTC. On multivariable analysis, older adults and super-elderly were 2.9 and 6.7 times more likely to have an increased DSM (HR:2.91, 95% CI: 1.83–4.63; p < 0.001 and HR: 6.70, 95%CI: 3.69–12.20; p < 0.001). Extent of surgery or lymphadenectomy did not affect DSM.ConclusionsIncreased age is an independent predictor of DSM in patients with MTC.     

Testicular Synovial Sarcoma:A Case Report

This paper reports a case of testicular synovial sarcoma with molecular genetic analysis.A 24-year-old male presented with painless scrotal mass.Ultrasonography showed a heterogeneous mass of 66 mm×34 mm in size involving the inguinal region.Histological examination of a surgical biopsy showed a gradeⅢmonophasic growth pattern of spindle cell proliferation.Immunohistochemical analyses indicated positive staining for pancytokeratine and epithelial membrane antigen.Cytogenetic analysis showed the presence of CYT-SSX1 mutation,and CT scan showed non-specific pleural micro-nodules with a size of 7.5 mm.The patient had an extended left orchidectomy but was lost to follow-up for 1 year.A local recurrent scrotal mass of 32 mm×25 mm,multiple inguinal lymph nodes,and increased pleural nodules,which were confirmed by histological examination,were treated with three cycles of adriamycine and ifosfamide chemotherapy,surgical resection,and radiotherapy with complete response.After 3 months,the patient developed local recurrence and pulmonary metastases that did not respond to second-line chemotherapy based on gemcitabine and paclitaxel.The patient had dyspnea at the time of this writing and chest pain,and is under third-line chemotherapy based on Deticene after 30 months of following up.This patient died on November 16,2012 after a resperatory failure and malignant plural effusion. Synovial sarcoma should be considered in the differential diagnosis of soft tissue tumor and it should be aggressively treated to improve prognosis.Although our patient has shown numerous factors of bad prognosis,he has had a relatively long survival time.     

Clinical and laboratory characteristics in septic arthritis patients with and without isolated germs

Background

The management of septic arthritis without bacteriological evidence is not well codified.

Pathway‐Based Association Study of Multiple Candidate Genes and Multiple Traits Using Structural Equation Models

There is increasing interest in the joint analysis of multiple genetic variants from multiple genes and multiple correlated quantitative traits in association studies. The classical approach involves testing univariate associations between genotypes and phenotypes and correcting for multiple testing that results in loss of power to detect associations. In this paper, we propose modeling complex relationships between genetic variants in candidate genes and measured correlated traits using structural equation models (SEM), taking advantage of prior knowledge on clinical and genetic pathways. We adopt generalized structured component analysis (GSCA) as an approach to SEM and develop a single association test between multiple genetic variants in a gene and a set of correlated traits, taking into account all available data from other genes and other traits. The performance of this test is investigated by simulations. We apply the proposed method to the Quebec Child and Adolescent Health and Social Survey (1999) data to investigate genetic associations with cardiovascular disease‐related traits.     

Dorsal costo-vertebral joint as a rare localization of Staphylococcus aureus sepsis

Background

Septic arthritis of the costovertebral thoracic joint is a rare site infection. We report an isolated case of septic arthritis of the 10th costo-vertebral right joint with osteitis due to Staphylococcus aureus.

Soft‐tissue tumor of the perineum: an exceptional case of bilateral perineal myoma

Perineal myomas in female are exceptional. We report the second case in literature of perineal myomas. It is a case of bilateral perineal myomas lifting the skin occurring in a female patient of 49 years old. She was operated by perineal incisions. Histopathology confirmed the fibromatous nature without signs of malignancy.