Genetic screening revealed usher syndrome in a paediatric Chinese patient.

INTRODUCTION: Usher syndrome is the most common cause of hereditary deaf-blindness. Three clinical subtypes have been classified. Usher syndrome type I is the most severe subtype characterized by congenital severe-to-profound hearing loss, retinitis pigmentosa and vestibular dysfunction. METHODS: One family was analyzed and the analysis included the combination of a custom capture/next-generation sequencing panel of 180 known deafness gene, Sanger sequencing and bioinformatics approaches. RESULTS: Compound heterozygous mutations in the MYO7A gene: a known missense mutation c.494C>T (p.Thr165Met) and a novel missense mutation c.6113G>A (p.Gly2038Glu) were identified in a proband. This Chinese hearing-impaired child was misdiagnosed as non-syndromic hearing loss which was later changed to the diagnosis of Usher syndrome type I after comprehensive audiometric, vestibular and ophthalmological examinations at 9 years old. CONCLUSIONS: Due to the features of genetic heterogeneity and variation in clinical manifestation, molecular diagnosis and ophthalmological examinations by skilled ophthalmologists with knowledge of Usher syndrome should be suggested as a routine assessment which may improve the accuracy and reliability of etiological diagnosis for hearing loss.

Identification of a de novo mutation of SOX10 in a Chinese patient with Waardenburg syndrome type IV.

OBJECTIVES: Waardenburg syndrome is a rare genetic disorder, characterized by the association of sensorineural hearing loss and pigmentation abnormalities. Four subtypes have been classified. The present study aimed to analyze the clinical feature and investigate the genetic cause for a Chinese case of Waardenburg type IV (WS4). METHODS: The patient and his family members were subjected to mutation detection in the candidate gene SOX10 by Sanger sequencing. RESULTS: The patient has the clinical features of WS4, including sensorineural hearing loss, bright blue irides, premature graying of the hair and Hirschsprung disease. A novel heterozygous frameshift mutation, c.752_753ins7 (p.Gly252Alafs*31) in the exon 5 of SOX10 was detected in the patient, but not found in the unaffected family members and 100 normal controls. This mutation results in a premature stop codon 31 amino acid downstream. CONCLUSIONS: The novel mutation c.752_753ins7 (p.Gly252Alafs*31) arose de novo and was considered as the cause of WS4 in the proband. This study further characterized the molecular complexity of WS4 and provided a clinical case for genotype-phenotype correlation studies of different phenotypes caused by SOX10 mutations.

HER2 FISH classification of equivocal HER2 IHC breast cancers with use of the 2013 ASCO/CAP practice guideline.

The status of human epidermal growth factor receptor 2 (HER2, ERBB2) determines the eligibility of breast cancer patients to receive HER2-targeted therapy. The majority of HER2 testing in the U.S. is performed using a combination of immunohistochemistry (IHC) screening followed by fluorescence in situ hybridization (FISH) for IHC equivocal cases. In 2013, the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) updated the guideline for HER2 testing. This study evaluates the impact of the 2013 ASCO/CAP updated guideline on final HER2 FISH classification of breast cancers with an equivocal IHC result. For each case, we reported a FISH result according to the 2013 updated guideline and recorded a separated result using the 2007 guideline for investigational purpose. McNemar's test and Bowker's symmetry test were used to compare the classifications by the two guidelines. Among 172 HER2 IHC 2+ equivocal cases, use of the 2103 guideline changed classifications in 36 cases (21 %) when compared with the results expected by use of the 2007 guideline, and yielded a higher proportion of positive (28.5 vs. 23.3 %) and equivocal (16.3 vs. 4.1 %), and a lower proportion of negative (55.2 vs. 72.7 %) cases (p < 0.001). The major classification change with use of the updated guideline is from the HER2 FISH negative to equivocal in 26 cases (15 %). Our study has shown that implementation of the 2013 ASCO/CAP updated guideline has significant impact on HER2 classification for breast cancers with an equivocal HER2 IHC result and therefore increased the use of HER2-targeted therapy. Our data have also shown that reflex FISH is effective for final classification of the IHC equivocal cases and that polysomy 17 (CEP17 copy number ≥3/cell) is present in a significantly higher proportion of cases with an equivocal HER2 FISH classification.

National estimates of seroincidence and seroprevalence for herpes simplex virus type 1 and type 2 among US military adults aged 18 to 29 years.

BACKGROUND: While population-based seroprevalence studies of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are widespread, seroincidence studies are largely limited to select or high-risk populations. The US military offers a potential population to derive national seroincidence rate estimates for young adults (ages 18-29). METHODS: We used banked, longitudinal serum specimens collected in a cohort of 1094 military personnel aged 18 to 30 years who served between 1989 and 2005 to estimate national HSV-1 and HSV-2 seroincidence and seroprevalence for the young, adult military population, weighted according to the US Census. Serum was tested with indirect ELISA (enzyme-linked immunosorbent assay). RESULTS: Estimated national seroincidence rates for the US young, adult military population were 9.1 per 100 person-years (95% confidence interval: 4.6-13.5) for HSV-1 and 6.2 (95% confidence interval: 3.1-9.3) for HSV-2. Female sex and black race were associated with significantly higher HSV-2 seroconversion rates. Our estimated HSV1/2 seroprevalences were comparable to US national data provided by National Health and Nutrition Examination Surveys' serosurveys except for non-Hispanic blacks and Hispanics. CONCLUSION: Although these US 2000 Census-weighted estimates of HSV-1 and HSV-2 seroincidence apply only to young, military adults, they nonetheless supply, to our knowledge, the only national figures that might be used to predict US national HSV1/2 seroincidence in young adults. Thus, we believe that our findings in this military population can be used to inform the planning of HSV-1 and 2 prevention measures in the general, young-adult US population.