Lymphangioma is a rare proliferation of the lymphatic system which is classified as either lymphangioma circumscription or carvenous lymphangioma. The involvement of the vulva is very rare and only a small number of case reports have been made on carvenous lymphangioma of the vulva. We herein report a case of 20-year-old unmarried girl presented with gradually expanding and painless tumor of the left labium majus. The mass was removed surgically and pathology confirmed as carvenous lymphangioma, with no recurrences to date.
Carvenous lymphangioma; Vulva neoplasms
Uterine arteriovenous malformation (AVM) is a rare entity in gynecology with fewer than 100 cases reported in the literature. Due to abnormal connection between arteries and veins without an intervening capillary system, recurrent and profuse vaginal bleeding is the most common symptom which can be potentially life-threatening. Uterine AVM can be either congenital or acquired. Acquired AVM is reported as a consequence of previous uterine trauma such as curettage procedures, caesarean section or pelvic surgery. It is also associated with infection, retained product of conception, gestational trophoblastic disease, malignancy and exposure to diethlystilboestrol. We herein report a case of acquired uterine AVM located on the right lateral wall after intrauterine instrumentation for laparoscopic left salpingectomy due to left tubal pregnancy. The patient was successfully treated with embolization.
Intrauterine instrumentation; Tubal pregnancy; Uterine arteriovenous malformation
Asian patients undergoing kidney transplantation (KT) generally have better renal allograft survival and a lower burden of cardiovascular disease than those of other racial groups. The KNOW-KT aims to explore allograft survival rate, cardiovascular events, and metabolic profiles and to elucidate the risk factors in Korean KT patients.
KNOW-KT is a multicenter, observational cohort study encompassing 8 transplant centers in the Republic of Korea. KNOW-KT will enroll 1,000 KT recipients between 2012 and 2015 and follow them up to 9 years. At the time of KT and at pre-specified intervals, clinical information, laboratory test results, and functional and imaging studies on cardiovascular disease and metabolic complications will be recorded. Comorbid status will be assessed by the age-adjusted Charlson co-morbidity index. Medication adherence and information on quality of life (QoL) will be monitored periodically. The QoL will be assessed by the Kidney Disease Quality of Life Short Form. Donors will include both living donors and deceased donors whose status will be assessed by the Kidney Donor Risk Index. Primary endpoints include graft loss and patient mortality. Secondary endpoints include renal functional deterioration (a decrease in eGFR to <30 mL/min/1.73 m2), acute rejection, cardiovascular event, albuminuria, new-onset diabetes after transplant, and QoL. Data on other adverse outcomes including episodes of infection, malignancy, recurrence of original renal disease, fracture, and hospitalization will also be collected. A bio-bank has been established for the acquisition of DNA, RNA, and protein from serum and urine samples of recipients at regular intervals. Bio-samples from donors will also be collected at the time of KT. KNOW-KT was registered in an international clinical trial registry (NCT02042963 at http://www.clinicaltrials.gov) on January 20th, 2014.
The KNOW-KT, the first large-scale cohort study in Asian KT patients, is expected to represent the Asian KT population and provide information on their natural course, complications, and risk factors for complications.
Cohort study; Complication; Kidney transplantation; KNOW-KT; Risk factor
To evaluate and compare the risks of secondary cancers from therapeutic doses received by patients with hepatocellular carcinoma (HCC) during intensity-modulated radiotherapy (IMRT), volumetric arc therapy (VMAT), and tomotherapy (TOMO).
Treatments for five patients with hepatocellular carcinoma (HCC) were planned using IMRT, VMAT, and TOMO. Based on the Biological Effects of Ionizing Radiation VII method, the excess relative risk (ERR), excess absolute risk (EAR), and lifetime attributable risk (LAR) were evaluated from therapeutic doses, which were measured using radiophotoluminescence glass dosimeters (RPLGDs) for each organ inside a humanoid phantom.
The average organ equivalent doses (OEDs) of 5 patients were measured as 0.23, 1.18, 0.91, 0.95, 0.97, 0.24, and 0.20 Gy for the thyroid, lung, stomach, liver, small intestine, prostate (or ovary), and rectum, respectively. From the OED measurements, LAR incidence were calculated as 83, 46, 22, 30, 2 and 6 per 104 person for the lung, stomach, normal liver, small intestine, prostate (or ovary), and rectum.
We estimated the secondary cancer risks at various organs for patients with HCC who received different treatment modalities. We found that HCC treatment is associated with a high secondary cancer risk in the lung and stomach.
HCC; IMRT; VMAT; Tomotherapy; Radiophotoluminescence; OED; EAR; ERR; LAR
The molecular interaction between tumor suppressor p53 and the anti-apoptotic Bcl-2 family proteins plays an essential role in the transcription-independent apoptotic pathway of p53. In this study, we investigated the binding of p53 DNA-binding domain (p53DBD) with the anti-apoptotic Bcl-2 family proteins, Bcl-w, Mcl-1, and Bcl-2, using GST pull-down assay and NMR spectroscopy. The GST pull-down assays and NMR experiments demonstrated the direct binding of the p53DBD with Bcl-w, Mcl-1, and Bcl-2. Further, NMR chemical shift perturbation data showed that Bcl-w and Mcl-1 bind to the positively charged DNA-binding surface of p53DBD. Noticeably, the refined structural models of the complexes between p53DBD and Bcl-w, Mcl-1, and Bcl-2 showed that the binding mode of p53DBD is highly conserved among the anti-apoptotic Bcl-2 family proteins. Furthermore, the chemical shift perturbations on Bcl-w, Mcl-1, and Bcl-2 induced by p53DBD binding occurred not only at the p53DBD-binding acidic region but also at the BH3 peptide-binding pocket, which suggests an allosteric conformational change similar to that observed in Bcl-XL. Taken altogether, our results revealed a structural basis for a conserved binding mechanism between p53DBD and the anti-apoptotic Bcl-2 family proteins, which shed light on to the molecular understanding of the transcription-independent apoptosis pathway of p53.
apoptosis; Bcl-2 family proteins; binding mechanism; DNA-binding domain; p53
Background: Our purpose was to provide the clinical advantages of the laparoscopic approach compare to the vaginal approach in correcting uterine and vaginal vault prolapse.
Methods: Between June 2007 and June 2011, 174 women were admitted to HUMC (Hallym University Medical Center) and underwent pelvic reconstructive surgery for prolapsed vaginal vault and uterus. Upon retrospective review of the medical records, 174 of the patients who had symptoms of pelvic organ prolapsed and Baden-Walker prolapse grade ≥ 2 were selected and divided into two groups as follows: vaginal approach group (n=120) and laparoscopic approach group (n=54). We compared the results of clinical outcome by analyzing Student's t-test and χ2-test or the Fisher exact test as appropriate.
Results: There were significant difference in success rates without reoperation for recurrence as 91.7% (vaginal approach group, n=110) vs 100% (laparoscopic approach group, n=54), p=0.032. Mean follow-up duration was 31.3 ± 7.6 months for vaginal approach group and 29.7 ± 9.7 months for laparoscopic approach group. The Foley catheter indwelling duration (4.7± 1.9 vs 3.4±2.1 days, p< 0.001) and the length of postoperative hospitalization (6.4 ± 2.1 vs 5.0 ± 1.9 days, p <0.001) were significantly longer in vaginal approach group, whereas the operative time was significantly longer (108.2 ± 38.6 vs 168.3 ± 69.7 minutes, p <0.001) in laparoscopic approach group.
Conclusions: Our result suggest there is significantly lower recurrence rate requiring reoperation and less catheterization time but increased operative time for laparascopic sacrocolpopexy.
uterine vaginal vault prolapse; pelvic reconstructive surgery; laparoscopy.
To compare the risk of secondary cancer from scattered and leakage doses following intensity-modulated radiotherapy (IMRT), volumetric arc therapy (VMAT) and tomotherapy (TOMO) in patients with lung cancer.
IMRT, VMAT and TOMO were planned for five lung cancer patients. Organ equivalent doses (OEDs) are estimated from the measured corresponding secondary doses during irradiation at various points 20 to 80 cm from the iso-center by using radio-photoluminescence glass dosimeter (RPLGD).
The secondary dose per Gy from IMRT, VMAT and TOMO for lung cancer, measured 20 to 80 cm from the iso-center, are 0.02~2.03, 0.03~1.35 and 0.04~0.46 cGy, respectively. The mean values of relative OED of secondary dose of VMAT and TOMO, which is normalized by IMRT, ranged between 88.63% and 41.59% revealing 88.63% and 41.59% for thyroid, 82.33% and 41.85% for pancreas, 77.97% and 49.41% for bowel, 73.42% and 72.55% for rectum, 74.16% and 81.51% for prostate. The secondary dose and OED from TOMO became similar to those from IMRT and VMAT as the distance from the field edge increased.
OED based estimation suggests that the secondary cancer risk from TOMO is less than or comparable to the risks from conventional IMRT and VMAT.
IMRT; VMAT; TOMOTHERAPY; Radio-photoluminescence; Secondary dose; OED
Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown.
Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry.
In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78–0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14–1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD.
Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. Neurology® 2012;79:659–667
Enteropathy-type T-cell lymphoma (ETTL) is a rare disease with a poor prognosis. According to the World Health Organization (WHO) classification, it is a subtype of the peripheral T-cell lymphomas. This disease is associated with gluten-sensitive enteropathy, has a high risk of intestinal perforation and obstruction, and is refractory to chemotherapeutic treatment. We report the case of a 73-year-old woman who was diagnosed with enteropathy-type T-cell lymphoma of the small intestine, which was positive for the markers of cytotoxic T cells, CD3, CD8, and CD56, on immunohistochemical staining after resection of the perforated terminal ileum.
Enteropathy-type T-cell lymphoma; celiac disease; intestinal perforation
In this paper, an improved algorithm for the extraction of respiration signal from the electrocardiogram (ECG) in home healthcare is proposed. The whole system consists of two-lead electrocardiogram acquisition using conductive textile electrodes located in bed, baseline fluctuation elimination, R-wave detection, adjustment of sudden change in R-wave area using moving average, and optimal lead selection. In order to solve the problems of previous algorithms for the ECG-derived respiration (EDR) signal acquisition, we are proposing a method for the optimal lead selection. An optimal EDR signal among the three EDR signals derived from each lead (and arctangent of their ratio) is selected by estimating the instantaneous frequency using the Hilbert transform, and then choosing the signal with minimum variation of the instantaneous frequency. The proposed algorithm was tested on 15 male subjects, and we obtained satisfactory respiration signals that showed high correlation (r2 > 0.8) with the signal acquired from the chest-belt respiration sensor.
Home healthcare; Conductive textile electrodes in bed; ECG-derived respiration; Instantaneous frequency; Hilbert transform
The expression of glucose transporter-1 (Glut-1) gene and those of major thyroid-specific genes were examined in papillary carcinoma tissues, and the expressions of these genes were compared with cancer differentiation grades.
Materials and Methods
Twenty-four human papillary carcinoma tissues were included in this study. The expressions of Glut-1- and thyroid-specific genes [sodium/iodide symporter (NIS), thyroid peroxidase, thyroglobulin, TSH receptor and pendrin] were analyzed by RT-PCR. Expression levels were expressed as ratios versus the expression of beta-actin. Pathologic differentiation of papillary carcinoma was classified into a relatively well-differentiated group (n = 13) and relatively less differentiated group (n = 11).
Glut-1 gene expression was significantly higher in the less differentiated group (0.66 ± 0.04) than in the well-differentiated group (0.59 ± 0.07). The expression levels of the NIS, PD and TG genes were significantly higher in the well-differentiated group (NIS: 0.67 ± 0.20, PD: 0.65 ± 0.21, TG: 0.74 ± 0.16) than in the less differentiated group (NIS: 0.36 ± 0.05, PD: 0.49 ± 0.08, TG: 0.60 ± 0.11), respectively. A significant negative correlation was found between Glut-1 and NIS expression, and positive correlations were found between NIS and TG, and between NIS and PD.
The NIS, PD and TG genes were highly expressed in well-differentiated thyroid carcinomas, whereas the Glut-1 gene was highly expressed in less differentiated thyroid carcinomas. These findings provide a molecular rationale for the management of papillary carcinoma, especially in the selection of FDG PET or radioiodine whole-body scan and I-131-based therapy.
Glucose transporter-1; Sodium/iodide symporter; Thyroid peroxidase; Thyroglobulin; TSH receptor; Pendrin; Papillary thyroid cancer
Self-induced hypoxia has been reported particularly in adolescents, and it can result in neurological injury. Here, we present a case of electroencephalogram (EEG) abnormalities induced by habitual neck compression differentiated from epileptic seizures by Tc-99m HMPAO SPECT. A 19-year-old male was admitted for evaluation of recurrent generalized tonic-clonic seizures. No interictal EEG abnormality was detected; however, abnormal slow delta waves were found immediately after habitual right neck compression. To differentiate EEG abnormalities due to a hemodynamic deficit induced by habitual neck compression from an epileptic seizure, Tc-99m HMPAO SPECT was performed immediately after right carotid artery compression. Abnormal delta waves were triggered, and cerebral hypoperfusion in the right internal carotid artery territory was detected on Tc-99m HMPAO SPECT. The slow delta wave detected on the EEG resulted from the cerebral hypoperfusion because of the habitual neck compression.
Habitual neck compression; Tc-99m HMPAO SPECT; Electroencephalogrm; Seizure
We report here the draft genome sequence of Arthrobacter sp. MWB30 strain, isolated from a crude oil-contaminated seashore in Tae-an, South Korea, which is able to degrade the crude oil and its derivatives. The draft genome sequence of 4,647,008 bp provides a resource for the identification of crude oil-degrading mechanisms in strain MWB30.
Obesity is one of the most significant risk factors for hypertension. However, there is controversy regarding which measure is the best predictor of hypertension risk. We compared body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) in subjects as predictive indicators for development of hypertension.
The data were obtained from the Korean Genome and Epidemiology Study (KoGES), a large population-based prospective cohort study. A total of 4,454 subjects (2,128 men and 2,326 women) aged 40–69 years who did not have hypertension at baseline were included in this study. Incident hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or anti-hypertensive medication use during the 4-year follow up. Receiver operating characteristic (ROC) analysis was used to compare discrimination abilities for anthropometric indices for hypertension. Hazard ratios were calculated by Cox proportional hazard model with adjustment for age, smoking status, alcohol consumption, diabetes and family history of hypertension by sexes.
In men, the area under the ROC curve (AROC) was 0.62 for WC, WHR, and WHtR and 0.58 for BMI. In women, the AROCs for BMI, WC, WHR, and WHtR were 0.57, 0.66, 0.68, and 0.68, respectively. After adjustment for risk factors, a 1 standard deviation increase in BMI, WC, WHR, WHtR were significantly related to incident hypertension, respectively (hazard ratio: 1.39, 1.50, 1.40 and 1.49 in men, 1.31, 1.44, 1.35 and 1.48 in women).
The central obesity indices WC, WHR, and WHtR were better than BMI for the prediction of hypertension in middle-aged Korean people. WHtR facilitates prediction of incident hypertension because of the single standard regardless of sex, ethnicity, and age group. Therefore, WHtR is recommended as a screening tool for the prediction of hypertension.
Obesity; Hypertension; Risk factors; Anthropometric indices
For binary or categorical response models, most goodness-of-fit statistics are based on the notion of partitioning the subjects into groups or regions and comparing the observed and predicted responses in these regions by a suitable chi-squared distribution. Existing strategies create this partition based on the predicted response probabilities, or propensity scores, from the fitted model. In this paper, we follow a retrospective approach, borrowing the notion of balancing scores used in causal inference to inspect the conditional distribution of the predictors, given the propensity scores, in each category of the response to assess model adequacy. This diagnostic can be used under both prospective and retrospective sampling designs and may ascertain general forms of misspecification. We first present simple graphical and numerical summaries that can be used in a binary logistic model. We then generalize the tools to propose model diagnostics for the proportional odds model. We illustrate the methods with simulation studies and two data examples (i) a case-control study of the association between cumulative lead exposure and Parkinson’s Disease in the Boston, Massachusetts area and (ii) and a cohort study of biomarkers possibly associated with diabetes, from the VA Normative Aging Study.
Balancing Score; Multinomial Logistic; Proportional Odds; Residual Diagnostic; Score Test
We present a new method for magnetization transfer (MT) ratio imaging in the brain that requires no separate saturation pulse. Interslice MT effects that are inherent to multi-slice balanced steady-state free precession (bSSFP) imaging were controlled via an interslice delay time to generate MT-weighted (0 s delay) and reference images (5–8 s delay) for MT ratio (MTR) imaging of the brain. The effects of varying flip angle and phase encoding (PE) order were investigated experimentally in normal, healthy subjects. Values of up to ∼50% and ∼40% were observed for white and gray matter MTR. Centric PE showed larger MTR, higher SNR, and better contrast between white and gray matter than linear PE. Simulations of a two-pool model of MT agreed well with in vivo MTR values. Simulations were also used to investigate the effects of varying acquisition parameters, and the effects of varying flip angle, PE steps, and interslice delay are discussed. Lastly, we demonstrated reduced banding with a non-balanced SSFP-FID sequence and showed preliminary results of interslice MTR imaging of meningioma.
The Wnt signaling pathway has regulatory roles in cell proliferation, differentiation, and polarity. Aberrant Wnt pathway regulation can lead to abnormal cell proliferation and cancer, and loss of Wnt7a expression has been demonstrated in lung cancer cell lines. E-cadherin keeps intercellular integrity and prevents metastasis. Therefore, E-cadherin has been known as a prognostic factor in cancer. In the present study, we investigated the E-cadherin expression status by immunohistochemical stain and the Wnt7a promoter methylation status in human non-small cell lung carcinoma (NSCLC) by methylation-specific PCR. We also analyzed their correlations with clinicopathological factors. Methylation of the Wnt7a gene promoter was detected in the lung tissues of 32 of 121 (26.4%) patients with NSCLC. Wnt7a promoter methylation was correlated with advanced tumor stage (P = 0.036) and distant metastasis (P = 0.037). In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001). However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit. Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.
Carcinoma, Non-small Cell Lung; Wnt7a; Biologic Markers; E-cadherin
Interventional device closure has emerged as a less invasive alternative to surgery in the management of paravalvular leakage. However, this procedure involves various problems such as a high probability of residual leakage or hemolysis. Here, we report a case of residual paravalvular leakage despite two attempts at interventional closure in a patient with a history of four previous mitral valve replacements. The fifth operation for the primary repair of paravalvular leakage was performed successfully. Careful evaluation before the procedure and specially designed devices are essential for the interventional treatment of paravalvular leakage. Surgery can be performed adequately in the management of paravalvular leakage even in high-risk patients.
Mitral valve; Mitral valve, replacement; Reoperation; Recurrence; Regurgitation
Two-dimensional (2D) molybdenum disulphide (MoS2) atomic layers have a strong potential to be used as 2D electronic sensor components. However, intrinsic synthesis challenges have made this task difficult. In addition, the detection mechanisms for gas molecules are not fully understood. Here, we report a high-performance gas sensor constructed using atomic-layered MoS2 synthesised by chemical vapour deposition (CVD). A highly sensitive and selective gas sensor based on the CVD-synthesised MoS2 was developed. In situ photoluminescence characterisation revealed the charge transfer mechanism between the gas molecules and MoS2, which was validated by theoretical calculations. First-principles density functional theory calculations indicated that NO2 and NH3 molecules have negative adsorption energies (i.e., the adsorption processes are exothermic). Thus, NO2 and NH3 molecules are likely to adsorb onto the surface of the MoS2. The in situ PL characterisation of the changes in the peaks corresponding to charged trions and neutral excitons via gas adsorption processes was used to elucidate the mechanisms of charge transfer between the MoS2 and the gas molecules.
labeling of peptides prior to shotgun proteomics allows
relative quantification of proteins in biological samples independent
of sample origin. Current strategies utilize isobaric labels that
fragment into reporter ions. However, quantification of reporter ions
results in distorted ratio measurements due to contaminating peptides
that are co-selected in the same precursor isolation window. Here,
we show that quantitation of isobaric peptide fragment isotopologues
in tandem mass spectra reduces precursor interference. The method
is based on the relative quantitation of isobaric isotopologues of
dimethylated peptide fragments in tandem mass spectra following higher
energy collisional dissociation (HCD). The approach enables precise
quantification of a proteome down to single spectra per protein and
quantifies >90% of proteins in a MudPIT experiment and accurately
measures proteins in a model cell line for cystic fibrosis.
proteomics; mass spectrometry
The best validated susceptibility variants for Parkinson’s disease (PD) are located in the alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) genes. Recently, a protective p.N551K-R1398H-K1423K haplotype in the leucine-rich repeat kinase 2 (LRRK2) gene was identified, with p.R1398H appearing to be the most likely functional variant. To date, the consistency of the protective effect of LRRK2 p.R1398H across MAPT and SNCA variant genotypes has not been assessed. To address this, we examined four SNCA variants (rs181489, rs356219, rs11931074, rs2583988), the MAPT H1-haplotype defining variant rs1052553, and LRRK2 p.R1398H (rs7133914) in Caucasian (N=10,322) and Asian (N=2,289) series. There was no evidence of an interaction of LRRK2 p.R1398H with MAPT or SNCA variants (all P≥0.10); the protective effect of p.R1398H was observed at similar magnitude across MAPT and SNCA genotypes, and the risk effects of MAPT and SNCA variants were observed consistently for LRRK2 p.R1398H genotypes. Our results indicate that the association of LRRK2 p.R1398H with PD is independent of SNCA and MAPT variants, and vice versa, in Caucasian and Asian populations.
Parkinson disease; LRRK2; SNCA; MAPT; interaction; genetics
Resistance to the BRAF inhibitor vemurafenib poses a significant problem for the treatment of BRAFV600E-positive melanomas. It is therefore critical to prospectively identify all vemurafenib-resistance mechanisms prior to their emergence in the clinic. The vemurafenib-resistance mechanisms described to date do not result from secondary mutations within BRAFV600E. To search for possible mutations within BRAFV600E that can confer drug resistance, we developed a systematic experimental approach involving targeted saturation mutagenesis, selection of drug-resistant variants, and deep sequencing. We identified a single nucleotide substitution (T1514A, encoding L505H) that greatly increased drug resistance in cultured cells and mouse xenografts. The kinase activity of BRAFV600E/L505H was higher than that of BRAFV600E, resulting in cross-resistance to a MEK inhibitor. However, BRAFV600E/L505H was less resistant to several other BRAF inhibitors whose binding sites were further from L505 than that of PLX4720. Our results identify a novel vemurafenib-resistant mutant and provide insights into the treatment of melanomas bearing this mutation.
BRAFV600E; deep sequencing; drug resistance; saturation mutagenesis; vemurafenib
CHARGE syndrome MIM #214800 is an autosomal dominant syndrome involving multiple congenital malformations. Clinical symptoms include coloboma, heart defects, choanal atresia, retardation of growth or development, genital hypoplasia, and ear anomalies or deafness. Mutations in the chromodomain helicase DNA binding protein 7 (CHD7) gene have been found in 65-70% of CHARGE syndrome patients. Here, we describe a 16-month-old boy with typical CHARGE syndrome, who was referred for CHD7 gene analysis. Sequence analysis and multiplex ligation-dependent probe amplification were performed. A heterozygous 38,304-bp deletion encompassing exon 3 with a 4-bp insertion was identified. There were no Alu sequences adjacent to the breakpoints, and no sequence microhomology was observed at the junction. Therefore, this large deletion may have been mediated by non-homologous end joining. The mechanism of the deletion in the current case differs from the previously suggested mechanisms underlying large deletions or complex genomic rearrangements in the CHD7 gene, and this is the first report of CHD7 deletion by this mechanism worldwide.
CHARGE syndrome; CHD7; Large deletion; Non-homologous end joining