A new nonsense mutation in the NF1 gene with neurofibromatosis–Noonan syndrome phenotype

Purpose

Neurofibromatosis–Noonan syndrome is a rare autosomal dominant disorder which combines neurofibromatosis type 1 (NF1) features with Noonan syndrome. NF1 gene mutations are reported in the majority of these patients.

Method

Sequence analysis of the established genes for Noonan syndrome revealed no mutation; a heterozygous NF1 point mutation c.7549C>T in exon 51, creating a premature stop codon (p.R2517X), had been demonstrated.

Result

Neurofibromatosis–Noonan syndrome recently has been considered a subtype of NF1 and caused by different NF1 mutations.

Conclusion

We report the case of a 14-year-old boy with neurofibromatosis type 1 with Noonan-like features, who complained of headache with triventricular hydrocephaly and a heterozygous NF1 point mutation c.7549C>T in exon 51.     

A novel NF1 gene mutation in an Italian family with neurofibromatosis type 1

Purpose

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder with an estimated incidence of one in 3,500 births. Clinically, NF1 is characterized by café-au-lait (CAL) spots, neurofibromas, freckling of the axillary or inguinal region, Lisch nodules, optic nerve glioma, and bone dysplasias. NF1 is caused by inactivating mutations of the 17q11.2-located NF1 gene. We present a clinical and molecular study of an Italian family with NF1.

Methods

The proband, a 10-year-old boy, showed large CAL spots and freckling on the axillary region and plexiform neurofibromas on the right side only. His father (47?years old) showed, in addition to the similar signs, numerous neurofibromas of various sizes on his thorax, abdomen, back, and shoulder. Two additional family members (a brother and a sister of the proband) presented only small CAL spots. The coding exons of NF1 gene were analyzed for mutations by denaturing high-performance liquid chromatography and sequencing in all family members.

Results

The mutational analysis of the NF1 gene revealed a novel frameshift insertion mutation in exon 4c (c.654 ins A) in all affected family members. This novel mutation creates a shift on the reading frame starting at codon 218 and leads to the introduction of a premature stop at codon 227.

Conclusions

The segregation of the mutation with the affected phenotype and its absence in the 200 normal chromosomes suggest that it is responsible for the NF1 phenotype.     

Suprasellar pilocytic astrocytoma: one national centre’s experience

Introduction

Pilocytic astrocytomas in the supratentorial compartment make up 20 % of all brain tumours in children with only 5 % of these arising in the suprasellar region. Optic pathway gliomas or suprasellar gliomas are often seen in neurofibromatosis type 1 (NF1) patients. Given their location, suprasellar pilocytic astrocytomas are challenging to manage surgically with high morbidity rates from surgical resection. We assess our cohort of patients with suprasellar pilocytic astrocytoma and document our experience.

Method

A retrospective review of patients diagnosed with suprasellar glioma between 2000–October 2012. We included patients diagnosed with optic pathway glioma based on radiological features (with or without biopsy) and those who had a biopsy confirming pilocytic astrocytoma.

Results

Fifty-three patients included (sporadic tumours 24 and NF1 related 29). Fifteen sporadic and four NF1 patients were biopsied. Twelve sporadic and 13 NF1 patients were initially treated with chemotherapy while only 1 patient had radiotherapy initially. Progression was noted in 58 % of the sporadic group and 24 % of the NF1 group. The only significant factor for progression was NF1 status (p?=?0.026).

Conclusion

Management should be guided by individual patient circumstance. In our cohort, chemotherapy did not significantly improve progression free survival; however, NF1 status significantly correlated with the decreased progression.     

Evaluation of the basal ganglia in neurofibromatosis type 1

Purpose

Alterations of the brain microstructure and metabolism have been identified in patients with neurofibromatosis type 1 (NF1). In this study, we analyzed the basal ganglia of NF1 subjects without cognitive delay throughout a combined approach with magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in order to better define the metabolic and microstructural characteristics of these regions and, furthermore, to verify if metabolic and microstructural abnormalities may be present in normally developed NF1 patients.

Methods

A 3-T MRI with multivoxel MRS and DTI was performed in 14 NF1 patients and eight controls. N-acetyl-aspartate (NAA), choline (Cho), creatine (Cr) values and ratios, fractional anisotropy, and apparent diffusion coefficient (ADC) were calculated, for a total of four regions of interest (ROI) for each hemisphere.

Results

NF1 patients, compared to healthy controls, showed (a) decreased NAA in all the four ROI, (b) increased Cho and decreased Cr in three of the four ROI, (c) decreased NAA/Cho ratio in three ROI, and (d) increased ADC in all the four ROI. A trend of increased ADC was present in three of the four ROI of NF1 patients with unidentified bright objects (UBOs) and younger than 18 years.

Conclusion

These data confirm the presence of neuroaxonal damage with myelin disturbances in NF1 patients. We showed that metabolic and microstructural anomalies can be present in the same time in NF1 patients without developmental delay or cognitive deficits. Relations between brain anomalies, UBOs, and cognitive functions need further studies.     

Neurofibromatosis type 1 (NF1) associated with tumor of the corpus callosum

Introduction

Neurofibromatosis type 1 (NF1), one of the most common neurocutaneous disorders, is a multisystemic disease associated with tumors in any organ of the body, especially in the central nervous system and also the peripheral nervous system. Pilocytic astrocytomas have been described in almost all intracranial regions in patients with NF1. However, only a few patients with NF1 and tumor of the corpus callosum have been reported to date.

Material and methods

An 11-year-old white Spanish boy was evaluated due to a family history of NF1 and low performance test scores in school. He was studied from the neurological and intellectual level points of view.

Results

Magnetic resonance (MR) study revealed a tumor in the anterior-middle portion of the corpus callosum and a Wechsler Intelligence Scale for Children-Revised showed verbal IQ of 92, a performance IQ of 108, and a total IQ of 100. In addition, he showed attention deficit and hyperactivity disorder.

Conclusions

Tumors of corpus callosum in patients with NF1 are very uncommon. The patient presented in this paper consulted due to family history of NF1, progressive hyperactivity, and below average school performance. The MR study showed tumor in the corpus callosum. Tumor histology was not investigated.     

Seizures in neurofibromatosis. What is the risk?

Introduction

The prevalence and the type of seizures associated with neurofibromatosis 1 (NF1) and 2 (NF2) are not adequately characterized.

State of the art

NF1 has a birth incidence of one in 2500, and NF2 one in 25000. Seizures are an occasional complication in NF1 patients and there is no data for NF2 patients. Central nervous system tumors are always suspected, since NF1 and NF2 are caused by mutations in tumor suppressor gene controlling cell proliferation and differentiation.

Perspectives

The aim of this article is to provide a synthetic overview about epilepsy associated with NF1 and NF2 based on published studies. In NF1, the type of seizures and their response to therapy are reported, the heterogeneity of etiology is also discussed. For NF2 patients, no specific data are available; the current knowledge comes from series of NF2 patients for which seizures has revealed the disease or from isolated case reports of tumors associated with seizures.

Conclusion

Cryptogenic epilepsy without anatomic defect is likely to be related to NF1, while seizures seem to be secondary to leptomeningeal tumors (meningioma, meningioangiomatosis) in NF2 patients.     

Is there relation between COL4A1/A2 mutations and antenatally detected fetal intraventricular hemorrhage?

Background

The aim of the present study is to evaluate the role of COL4A1/A2 mutations in the etiology of intraventricular hemorrhage (IVH) detected in-utero.

Methods

The data of four cases with fetal IVH were analyzed retrospectively. Antenatal risk factors, clinical features, postnatal outcome, and the presence of COL4A1/A2 mutations were evaluated.

Results

Eight cases of fetal IVH were diagnosed between 2005 and 2012 in Erciyes University. Of these, four were eligible for genetic analysis. Mean gestational age at diagnosis was 30 weeks 5 day (min–max: 28–34 weeks); two cases had grade III hemorrhage and two cases had grade IV hemorrhage according to fetal magnetic resonance imaging. Three cases had severe neurodevelopmental delay and one case had mild deficit. In all cases, postnatal evaluation revealed no underlying cause, and no retinal hemorrhagia and hematuria were detected. The mean postnatal follow-up was 19 months, and no recurrent hemorrhages and porencephalic cyst formation were observed. The whole exome sequencing showed no pathological mutations of COL4A1 and COL4A2 in the four patients.

Conclusion

Our data showed that fetal intraventricular hemorrhage is not associated with COL4A1 and COL4A2 mutations in the absence of porencephaly, recurrent hemorrhage, and other organ bleeding.     

Factors predictive of alcohol use during pregnancy in three rural states

Background

Conflicting associations with heroin dependence have been found involving the A1 allele of dopamine D2 receptor gene (DRD2) TaqI A polymorphism.

Methods

We compared two samples of unrelated Spanish individuals, all of European origin: 281 methadone-maintained heroin-dependent patients (207 males and 74 females) who frequently used non-opioid substances, and 145 control subjects (98 males and 47 females).

Results

The A1-A1 genotype was detected in 7.1% of patients and 1.4% of controls (P = 0.011, odds ratio = 5.48, 95% CI 1.26–23.78). Although the A1 allele was not associated with heroin dependence in the entire sample, the frequency of A1 allele was higher in male patients than in male controls (24.4% vs. 16.3%, P = 0.024, odds ratio = 1.65, 95% CI 1.07–2.57). A logistic regression analysis showed an interaction between DRD2 alleles and gender (odds ratio = 1.77, 95% CI 1.15–2.70).

Conclusion

Our results indicate that, in Spanish individuals, genotypes of the DRD2 TaqI A polymorphism contribute to variations in the risk of heroin dependence, while single alleles contribute only in males.     

Genetic analysis of the UPB1 gene in two new Chinese families with β-ureidopropionase deficiency and the carrier frequency of the mutation c.977G>A in Northern China

Purpose

The purpose of the study was to investigate mutations of the UPB1 gene in two Chinese families with β-ureidopropionase deficiency and the heterozygous carrier frequency in Chinese.

Methods

Genomic DNA was extracted from peripheral blood leukocytes from all available family members and 500 unrelated healthy controls. Then, all exons and flanking intron regions of the UPB1 gene were amplified by PCR and analyzed by direct sequencing in two patient-families. Finally, the carrier frequency of the c.977G>A (p.R326Q) mutation was identified by PCR restriction fragment length polymorphism in 500 healthy controls.

Results

The two patients had the same homozygous missense mutation in exon 9 (c.977G>A; p.R326Q), and the carrier frequency of this mutation was 2.8 % in the Northern Chinese population, which suggests that about 1:5,102 Chinese are expected to suffer from UPB1 deficiency.

Conclusions

The c.977G>A (p.R326Q) is the most common mutation of the UPB1 gene in Chinese. The predicted incidence indicates that β-ureidopropionase deficiency is significantly underdiagnosed in the Chinese population. It should be necessary to add β-ureidopropionase deficiency to high-risk screening for the symptomatic patients group.     

Gyrification,cortical and subcortical morphometry in neurofibromatosis type 1: an uneven profile of developmental abnormalities

Background

Neurofibromatosis type 1 (NF1) is a monogenic disorder associated with cognitive impairments. In order to understand how mutations in the NF1 gene impact brain structure it is essential to characterize in detail the brain structural abnormalities in patients with NF1. Previous studies have reported contradictory findings and have focused only on volumetric measurements. Here, we investigated the volumes of subcortical structures and the composite dimensions of the cortex through analysis of cortical volume, cortical thickness, cortical surface area and gyrification.

Methods

We studied 14 children with NF1 and 14 typically developing children matched for age, gender, IQ and right/left-handedness. Regional subcortical volumes and cortical gyral measurements were obtained using the FreeSurfer software. Between-group differences were evaluated while controlling for the increase in total intracranial volume observed in NF1.

Results

Subcortical analysis revealed disproportionately larger thalami, right caudate and middle corpus callosum in patients with NF1. Cortical analyses on volume, thickness and surface area were however not indicative of significant alterations in patients. Interestingly, patients with NF1 had significantly lower gyrification indices than typically developing children primarily in the frontal and temporal lobes, but also affecting the insula, cingulate cortex, parietal and occipital regions.

Conclusions

The neuroanatomic abnormalities observed were localized to specific brain regions, indicating that particular areas might constitute selective targets for NF1 gene mutations. Furthermore, the lower gyrification indices were accompanied by a disproportionate increase in brain size without the corresponding increase in folding in patients with NF1. Taken together these findings suggest that specific neurodevelopmental processes, such as gyrification, are more vulnerable to NF1 dysfunction than others. The identified changes in brain organization are consistent with the patterns of cognitive dysfunction in the NF1 phenotype.     

Syndromic craniosynostosis, fibroblast growth factor receptor 2 (FGFR2) mutations, and sacrococcygeal eversion presenting as human tails

Introduction

There have been 23 previously published cases of patients with syndromic craniosynostosis and human tails. In many of these, the tail was composed of prominent coccygeal and sacral vertebrae, curved in a retroverted instead of in the normal anterograde fashion. This has been termed sacrococcygeal eversion. In those cases in which genetic testing results are reported, there were fibroblast growth factor receptor 2 (FGFR2) mutations.

Methods

We present three patients with Pfeiffer syndrome and sacrococcygeal eversion. Two had genetic testing and both had FGFR2 mutations, one of them a novel mutation in patients with syndromic craniosynostosis and sacrococcygeal eversion. We also briefly review the literature on craniosynostosis and human tails.

Results

All but one reported patient has had either Pfeiffer, Crouzon, or Beare-Stevenson syndrome. Most patients, including ours, have had severe manifestations of their syndrome. Although the pathogenesis of sacrococcygeal eversion is unknown, a similarly posteriorly curved tail bud develops in normal human embryos during the second month of gestation.

Conclusions

Perhaps increased FGFR2 activation during this embryonic period leads to abnormal differentiation or regression of the tail bud and, in turn, sacrococcygeal eversion, in certain patients with severe syndromic craniosynostosis.     

Subependymal nodules and giant cell tumours in tuberous sclerosis complex patients: prevalence on MRI in relation to gene mutation

Purpose

The purpose of this study was to estimate the association among the presence of subependymal nodules (SENs), subependymal giant cell tumours (SGCTs) and gene mutation in tuberous sclerosis complex (TSC) patients.

Methods

Clinical records and images of 81 TSC patients were retrospectively reviewed by two neuroradiologists in consensus. All patients were assessed for gene mutations and were categorized as TSC1 or TSC2 mutation carriers, or no-mutations-identified (NMI) patients. They underwent a brain magnetic resonance imaging (MRI) using 0.1 mmol/kg of gadobutrol. Any enhancing SEN?≥?1 cm and placed near the foramen of Monro was considered SGCT. Two MRI follow-up exams for each patient with SGCT were evaluated to assess tumour growth using Wilcoxon and chi-squared tests.

Results

Of 81 patients, 44 (54 %) were TSC2 mutation carriers, 20 (25 %) TSC1 and 17 (21 %) NMI. Nine (11 %) had a unilateral and three (4 %) a bilateral SGCT. Fifty of 81 patients (62 %) showed at least one SEN. None of the 31 patients without SEN showed SGCTs, whilst 12 (24 %) of the 50 patients with at least one SEN showed SGCTs (p?=?0.003). The association between the presence of SGCT or SEN and gene mutation was not significant (p?=?0.251 and p?=?0.187, respectively). At follow-up, the median SGCT diameter increased from 14 to 15 mm (p?=?0.017), whilst the median SGCT volume increased from 589 to 791 mm³ (p?=?0.006).

Conclusions

TSC patients with SENs are more likely to present with SGCT than those without SENs, in particular for TSC2 mutation carriers. The SGCT growth rate may be missed if based on the diameter instead of on the volume.     

Impact of genetics on the diagnosis and clinical management of syndromic craniosynostoses

Purpose

More than 60 different mutations have been identified to be causal in syndromic forms of craniosynostosis. The majority of these mutations occur in the fibroblast growth factor receptor 2 gene (FGFR2). The clinical management of syndromic craniosynostosis varies based on the particular causal mutation. Additionally, the diagnosis of a patient with syndromic craniosynostosis is based on the clinical presentation, signs, and symptoms. The understanding of the hallmark features of particular syndromic forms of craniosynostosis leads to efficient diagnosis, management, and long-term prognosis of patients with syndromic craniosynostoses.

Methods

A comprehensive literature review was done with respect to the major forms of syndromic craniosynostosis and additional less common FGFR-related forms of syndromic craniosynostosis. Additionally, information and data gathered from studies performed in our own investigative lab (lab of Dr. Muenke) were further analyzed and reviewed. A literature review was also performed with regard to the genetic workup and diagnosis of patients with craniosynostosis.

Results

Patients with Apert syndrome (craniosynostosis syndrome due to mutations in FGFR2) are most severely affected in terms of intellectual disability, developmental delay, central nervous system anomalies, and limb anomalies. All patients with FGFR-related syndromic craniosynostosis have some degree of hearing loss that requires thorough initial evaluations and subsequent follow-up.

Conclusions

Patients with syndromic craniosynostosis require management and treatment of issues involving multiple organ systems which span beyond craniosynostosis. Thus, effective care of these patients requires a multidisciplinary approach.     

Posterior fossa tumors in children with neurofibromatosis type 1 (NF1)

Background

Tumours of the posterior fossa associated with neurofibromatosis type 1 (NF1) are very infrequent. Series studying this association are seldom reported.

Personal experience

In a series of 600 NF1 patients studied during 39 years (1965-2004) only five (0.83%) had posterior fossa tumours. They were studied clinically, radiologically by computerized tomography (CT) or magnetic resonance (MR) and histologically. Four of them had astrocytomas but only in one case was the tumour primarily cerebellar while the tumour was primarily of the brain stem with invasion of the adjacent regions of one or both cerebellar hemispheres in three patients. The fifth tumour was a medulloblastoma that had a survival of 3 years following treatment. The patient with primary cerebellar astrocytoma is apparently cured 7 years after the removal of the tumour. The patients with the brain stem tumours extending to the cerebellum, showed a chronic slowly progressive cerebellar disease, but remain alive at age of more than 20 years (one was lost to follow-up).

Discussion and conclusion

The aim of this study was to present five children (one male and four females) less than 16 years of age when they were initially seen in our service, who had NF1 associates with posterior fossa tumours. This location is very uncommon in patients with NF1, in contrast with those located in other regions, such as pathway optic tumours and brain stem tumours. Most of these tumours are histologically benign (low grade astrocytomas). Only one patient in this series had a medulloblastoma, an exceptionally rare tumour seldom reported in patients with NF1.     

New Genes Causing Hereditary Parkinson’s Disease or Parkinsonism

Purpose of Review

This article reviews genes where putative or confirmed pathogenic mutations causing Parkinson’s disease or Parkinsonism have been identified since 2012, and summarizes the clinical and pathological picture of the associated disease subtypes.

Recent Findings

Newly reported genes for dominant Parkinson’s disease are DNAJC13, CHCHD2, and TMEM230. However, the evidence for a disease-causing role is not conclusive, and further genetic and functional studies are warranted. RIC3 mutations have been reported from one family but not yet encountered in other patients. New genes for autosomal recessive disease include SYNJ1, DNAJC6, VPS13C, and PTRHD1. Deletions of a region on chromosome 22 (22q11.2del) are also associated with early-onset PD, but the mode of inheritance and the underlying causative gene remain unclear. PODXL mutations were reported in autosomal recessive PD, but their roles remain to be confirmed. Mutations in RAB39B cause an X-linked Parkinsonian disorder.

Summary

Mutations in the new dominant PD genes have generally been found in medium- to late-onset Parkinson’s disease. Many mutations in the new recessive and X-chromosomal genes cause severe atypical juvenile Parkinsonism, but less devastating mutations in these genes may cause PD.

     

IDH1 mutations are common in malignant gliomas arising in adolescents: a report from the Children��s Oncology Group

Purpose

Recent studies have demonstrated a high frequency of IDH mutations in adult ??secondary?? malignant gliomas arising from preexisting lower grade lesions, often in young adults, but not in ??primary?? gliomas. Because pediatric malignant gliomas share some molecular features with adult secondary gliomas, we questioned whether a subset of these tumors also exhibited IDH mutations.

Experimental design

We examined the frequency of IDH mutations, using real-time polymerase chain reaction and sequencing analysis, in a cohort of 43 pediatric primary malignant gliomas treated on the Children??s Oncology Group ACNS0423 study. The relationship between IDH mutations and other molecular and clinical factors, and outcome, was evaluated.

Results

IDH1 mutations were observed in 7 of 43 (16.3%) tumors; no IDH2 mutations were observed. A striking age association was apparent in that mutations were noted in 7 of 20 tumors (35%) from children ??14?years, but in 0 of 23 (0%) younger children (p?=?0.0024). No association was observed with clinical factors other than age. One-year event-free survival was 86?±?15% in the IDH-mutated group versus 64?±?8% in the non-mutated group (p?=?0.03, one-sided logrank test). One-year overall survival was 100% in patients with mutations versus 81?±?6.7% in those without mutations (p?=?0.035, one-sided logrank test).

Conclusions

IDH1 mutations are common in malignant gliomas in older children, suggesting that a subset of these lesions may be biologically similar to malignant gliomas arising in younger adults and may be associated with a more favorable prognosis.     

PINK1 mutation heterozygosity and the risk of Parkinson's disease

Background

Mutations in the PTEN‐induced kinase 1 (PINK1) gene have been identified in recessively inherited and sporadic early‐onset parkinsonism (EOP).

Methods

A total of 131 Norwegian patients diagnosed with Parkinson''s disease were included. Of them, 89 participants had EOP (onset ⩽50 years); the remaining had familial late‐onset disease (mean age at onset 64 years). PINK1 analysis included sequencing and gene dose assessment. Mutations were examined in 350 controls .

Results

Heterozygous missense mutations in PINK1 were found in 3 of 131 patients; none of the patients carried homozygous or compound heterozygous mutations. One of these three patients had a father affected by Parkinson''s disease, and he carried the mutation. Three new and seven known polymorphic variants were identified, although none seemed to be associated with disease risk.

Conclusions

PINK1 mutations are rare in Norwegian patients with EOP and familial Parkinson''s disease. However, the data suggest that some heterozygous mutations might increase the risk of developing Parkinson''s disease.The causes of Parkinson''s disease are still largely unknown. Evidence suggests that both environmental factors and genetic susceptibility contribute to disease aetiology.¹ Familial parkinsonism can be inherited as an autosomal dominant or recessive trait. Mutations in three genes have been associated with recessively inherited early‐onset parkinsonism (EOP): parkin, DJ‐1 and PTEN‐induced kinase 1 (PINK1). Mutations in the parkin gene may account for nearly 50% of familial and a considerable proportion of apparently sporadic EOP (with age of onset ⩽45 years).² Pathogenic mutations in the DJ‐1 gene seem to be rare, causing <1% of EOP cases.³Missense mutations in the PINK1 gene were first identified in three consanguineous Italian and Spanish kindreds affected with EOP.⁴ Mutations in this gene have now been found in families originating from several European and Asian populations, making PINK1 the second most common genetic known cause of EOP.^5,6,7,8,9PINK1 mutations have also been identified in patients with sporadic disease, including heterozygous mutations of unknown pathogenicity.^10,11 To further evaluate the pathogenic role of PINK1 mutations in familial and sporadic Parkinson''s disease, we performed a comprehensive mutation analysis of this gene in a series of Norwegian patients with Parkinson''s disease.     

Associations Between Socioeconomic Status and Catecholamine Levels Vary by Acculturation Status in Mexican-American Women

Background

Lower socioeconomic status (SES) is associated with poorer health, possibly through activation of the sympathetic nervous system.

Purpose

This study aimed to examine the association between SES and catecholamine levels, and variations by acculturation.

Methods

Three hundred one Mexican-American women underwent examination with a 12-h urine collection. Analyses tested associations of SES, acculturation (language and nativity), and their interaction with norepinephrine (NOREPI) and epinephrine (EPI).

Results

No main effects for SES or the acculturation indicators emerged. Fully adjusted models revealed a significant SES by language interaction for NOREPI (p?<?.01) and EPI (p?<?.05), and a SES by nativity interaction approached significance for NOREPI (p?=?.05). Simple slope analyses revealed that higher SES related to lower catecholamine levels in Spanish-speaking women, and higher NOREPI in English-speaking women. Although nonsignificant, similar patterns were observed for nativity.

Conclusions

Associations between SES and catecholamines may vary by acculturation, and cultural factors should be considered when examining SES health effects in Hispanics.     

Contemplating Genetic Feedback Regarding Lung Cancer Susceptibility

Background and Purpose

We examined three theoretical models (self-enhancement theory, consistency theory, and a combined model) for understanding how expectations and test result favorability influence smokers' desire for a retest following hypothetical genetic test results.

Method

College smokers (N?=?128) read a brochure describing a biomarker for lung cancer (the GSTM1 gene) then reported whether they thought they had the gene (indicating lower lung cancer risk) or were missing the gene (indicating higher lung cancer risk). Participants then reported whether they would get retested if they received favorable GSTM1 results versus unfavorable GSTM1 results.

Results

Participants were most likely to want a retest, suggesting rejection of the results, if they expected favorable news yet received unfavorable news.

Conclusion

The findings supported the combined model such that smokers expressed greatest interest in a retest when they imagined genetic risk feedback that challenges both enhancement and consistency motives.     

The association of NF2 (neurofibromin 2) gene polymorphism and the risk of medulloblastomas

To explore the relationship between NF2 promoter gene mutation and the risk of medulloblastomas (MBs). We collected tissues from 16 MB patients and 7 age-matched non-MB controls. Gene sequencing, qPCR (real-time quantitative polymerase chain reaction), IHC (immunohistochemistry), and WB (Western blot) were used to analyze the changes in the NF2 gene sequence and expression between patients and controls. We found that NF2 promoter gene mutations occurred in MB patients. The NF2 mRNA expression was higher in the controls than in patients (p?=?0.03?<?0.05); however, the results of IHC and WB demonstrated that the NF2 protein expression was significantly higher in patients than in the controls (IHC: p?=?0.0001; WB: p?=?0.01). There was no significant difference in the CRL4 mRNA and protein levels. In addition, NF2 protein was mainly expressed in the nucleus in MB patients, while the NF2 protein was mainly expressed in the cytoplasm in the controls. NF2 promoter mutations exist in MB patients. NF2 mRNA expression was higher in controls than patients; whereas NF2 protein level was higher in patients than in controls.