Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Genet Couns ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793699

RESUMO

Prenatal genetic screening should be an informed, autonomous patient choice. Extrinsic factors which influence patient decision-making threaten the ethical basis of prenatal genetic screening. Prior research in the area of medical decision-making has identified that labeling may have unanticipated effects on patient perceptions and decision-making processes. This Internet-administered study explored the impact of option labeling on the noninvasive prenatal screening (NIPS) selections of US adults. A total of 1,062 participants were recruited through Amazon Mechanical Turk (MTurk) and randomly assigned to one of three possible label sets reflecting provider-derived and industry-derived option labels used in prenatal screening. Multinomial logistic regression analysis showed option labeling had a statistically significant impact on the NIPS selections of study participants (p = .0288). Outcomes of the Satisfaction with Decision Scale (SWD) indicated option labels did not play a role in participant satisfaction with screening selection. The results of this study indicate a need for further evaluation of the impact NIPS option labeling has on patient screening decisions in real-world clinical interactions. Clinical providers and testing laboratories offering NIPS should give careful consideration to the option labels used with prenatal screening so as to minimize influence on patient screening selection and decision-making processes.

2.
Genet Med ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31607746

RESUMO

PURPOSE: We investigated the value of transcriptome sequencing (RNAseq) in ascertaining the consequence of DNA variants on RNA transcripts to improve the diagnostic rate from exome or genome sequencing for undiagnosed Mendelian diseases spanning a wide spectrum of clinical indications. METHODS: From 234 subjects referred to the Undiagnosed Diseases Network, University of California-Los Angeles clinical site between July 2014 and August 2018, 113 were enrolled for high likelihood of having rare undiagnosed, suspected genetic conditions despite thorough prior clinical evaluation. Exome or genome sequencing and RNAseq were performed, and RNAseq data was integrated with genome sequencing data for DNA variant interpretation genome-wide. RESULTS: The molecular diagnostic rate by exome or genome sequencing was 31%. Integration of RNAseq with genome sequencing resulted in an additional seven cases with clear diagnosis of a known genetic disease. Thus, the overall molecular diagnostic rate was 38%, and 18% of all genetic diagnoses returned required RNAseq to determine variant causality. CONCLUSION: In this rare disease cohort with a wide spectrum of undiagnosed, suspected genetic conditions, RNAseq analysis increased the molecular diagnostic rate above that possible with genome sequencing analysis alone even without availability of the most appropriate tissue type to assess.

3.
J Genet Couns ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31478310

RESUMO

BACKGROUND: Despite growing evidence of diagnostic yield and clinical utility of whole exome sequencing (WES) in patients with undiagnosed diseases, there remain significant cost and reimbursement barriers limiting access to such testing. The diagnostic yield and resulting clinical actions of WES for patients who previously faced insurance coverage barriers have not yet been explored. METHODS: We performed a retrospective descriptive analysis of clinical WES outcomes for patients facing insurance coverage barriers prior to clinical WES and who subsequently enrolled in the Undiagnosed Diseases Network (UDN). Clinical WES was completed as a result of participation in the UDN. Payer type, molecular diagnostic yield, and resulting clinical actions were evaluated. RESULTS: Sixty-six patients in the UDN faced insurance coverage barriers to WES at the time of enrollment (67% public payer, 26% private payer). Forty-two of 66 (64%) received insurance denial for clinician-ordered WES, 19/66 (29%) had health insurance through a payer known not to cover WES, and 5/66 (8%) had previous payer denial of other genetic tests. Clinical WES results yielded a molecular diagnosis in 23 of 66 patients (35% [78% pediatric, 65% neurologic indication]). Molecular diagnosis resulted in clinical actions in 14 of 23 patients (61%). CONCLUSIONS: These data demonstrate that a substantial proportion of patients who encountered insurance coverage barriers to WES had a clinically actionable molecular diagnosis, supporting the notion that WES has value as a covered benefit for patients who remain undiagnosed despite objective clinical findings.

4.
Clin Genet ; 96(6): 521-531, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31448412

RESUMO

While genomic sequencing (ES/GS) has the potential to diagnose children with difficult to diagnose phenotypes, the goal should be not only a diagnosis, but also to empower parents to seek next steps for their children and to emotionally manage the outcome, whether or not a diagnosis is secured. To help achieve this goal, objective measures are needed to assess the process of parental empowerment related to genome sequencing. We present the validity and reliability of the Genome Empowerment Scale (GEmS), developed using a healthcare empowerment theoretical model. To evaluate its psychometric properties, 158 parents of 117 children with an undiagnosed condition undergoing genomic sequencing completed the GEmS, measures for criterion validity and for depression and anxiety. Factor analysis resulted in a four factor solution: (a) meaning of a diagnosis; (b) emotional management of the process; (c) seeking information and support and (d) implications and planning. Reliability and validity analyses show that the GEmS has good psychometric properties. The inter-relationships among the factors revealed a profile that may identify parents at risk for a poorer outcome who may benefit from targeted genetic counseling. The GEmS, an objective measure of parental genomic empowerment, can be utilized for future research and translational applications.

5.
Hum Mutat ; 40(7): 908-925, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30817854

RESUMO

Pathogenic de novo variants in the X-linked gene SLC35A2 encoding the major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2-congenital disorders of glycosylation (CDG; formerly CDG-IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N-glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2-CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2-dependent UDP-galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild-type to mutant alleles in fibroblasts from affected individuals.

6.
J Genet Couns ; 28(2): 194-201, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30680851

RESUMO

The "diagnostic odyssey" is well known and described in genetic counseling literature. Studies addressing the psychological, emotional, and financial costs of not having a diagnosis have shown how it permeates the lives of patients and families. The Undiagnosed Diseases Network aims to end this odyssey by providing diagnoses to individuals with undiagnosed conditions through multidisciplinary evaluations, whole exome and genome sequencing, and basic science research. It also provides an opportunity to learn from patients and families and to better understand their journeys and the impact of receiving a diagnosis. Seven cases are presented that outline challenges that come from working with chronically undiagnosed and newly diagnosed patients in a time when sequencing for clinical diagnosis is rapidly increasing. They illuminate the emotional journey of patients and families searching for a diagnosis and the mental health problems, financial distress, and chaos that can accompany not having answers. They also illustrate the surprising reactions patients and families can have to receiving a diagnosis, including anger, grief, and disappointment. While the lessons learned from these families are not novel, new strategies are presented for handling these challenges in undiagnosed and ultra-rare populations, groups that will increase with the rise of clinical sequencing.

7.
N Engl J Med ; 379(22): 2131-2139, 2018 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-30304647

RESUMO

BACKGROUND: Many patients remain without a diagnosis despite extensive medical evaluation. The Undiagnosed Diseases Network (UDN) was established to apply a multidisciplinary model in the evaluation of the most challenging cases and to identify the biologic characteristics of newly discovered diseases. The UDN, which is funded by the National Institutes of Health, was formed in 2014 as a network of seven clinical sites, two sequencing cores, and a coordinating center. Later, a central biorepository, a metabolomics core, and a model organisms screening center were added. METHODS: We evaluated patients who were referred to the UDN over a period of 20 months. The patients were required to have an undiagnosed condition despite thorough evaluation by a health care provider. We determined the rate of diagnosis among patients who subsequently had a complete evaluation, and we observed the effect of diagnosis on medical care. RESULTS: A total of 1519 patients (53% female) were referred to the UDN, of whom 601 (40%) were accepted for evaluation. Of the accepted patients, 192 (32%) had previously undergone exome sequencing. Symptoms were neurologic in 40% of the applicants, musculoskeletal in 10%, immunologic in 7%, gastrointestinal in 7%, and rheumatologic in 6%. Of the 382 patients who had a complete evaluation, 132 received a diagnosis, yielding a rate of diagnosis of 35%. A total of 15 diagnoses (11%) were made by clinical review alone, and 98 (74%) were made by exome or genome sequencing. Of the diagnoses, 21% led to recommendations regarding changes in therapy, 37% led to changes in diagnostic testing, and 36% led to variant-specific genetic counseling. We defined 31 new syndromes. CONCLUSIONS: The UDN established a diagnosis in 132 of the 382 patients who had a complete evaluation, yielding a rate of diagnosis of 35%. (Funded by the National Institutes of Health Common Fund.).

8.
J Genet Couns ; 27(5): 1087-1101, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29497923

RESUMO

The burden of living with an undiagnosed condition is high and includes physical and emotional suffering, frustrations, and uncertainty. For patients and families experiencing these stressors, higher levels of empowerment may be associated with better outcomes. Thus, it is important to understand the experiences of patients with undiagnosed conditions and their families affected by undiagnosed conditions in order to identify strategies for fostering empowerment. In this study, we used the Genetic Counseling Outcome Scale (GCOS-24) to assess levels of empowerment and support group participation in 35 adult participants and 67 parents of child participants in the Undiagnosed Diseases Network (UDN) prior to their UDN in-person evaluation. Our results revealed significantly lower empowerment scores on the GCOS-24 in adult participants compared to parents of child participants [t(100) = - 3.01, p = 0.003, average difference = - 11.12, 95% CI (- 3.78, - 18.46)] and no significant association between support group participation and empowerment scores. The majority of participants (84.3%, 86/102) are not currently participating in any support groups, and participation rates were not significantly different for adult participants and parents of child participants (11.4 vs. 19.7%, respectively, FE p = 0.40). Open-ended responses provided additional insight into support group participation, the challenges of living with undiagnosed conditions, and positive coping strategies. Future research will evaluate the extent to which empowerment scores change as participation in the UDN unfolds.

9.
Disabil Health J ; 10(1): 23-32, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27594054

RESUMO

INTRODUCTION: Deaf American Sign Language-users (ASL) have limited access to cancer genetics information they can readily understand, increasing risk for health disparities. We compared effectiveness of online cancer genetics information presented using a bilingual approach (ASL with English closed captioning) and a monolingual approach (English text). HYPOTHESIS: Bilingual modality would increase cancer genetics knowledge and confidence to create a family tree; education would interact with modality. METHODS: We used a parallel 2:1 randomized pre-post study design stratified on education. 150 Deaf ASL-users ≥18 years old with computer and internet access participated online; 100 (70 high, 30 low education) and 50 (35 high, 15 low education) were randomized to the bilingual and monolingual modalities. Modalities provide virtually identical content on creating a family tree, using the family tree to identify inherited cancer risk factors, understanding how cancer predisposition can be inherited, and the role of genetic counseling and testing for prevention or treatment. 25 true/false items assessed knowledge; a Likert scale item assessed confidence. Data were collected within 2 weeks before and after viewing the information. RESULTS: Significant interaction of language modality, education, and change in knowledge scores was observed (p = .01). High education group increased knowledge regardless of modality (Bilingual: p < .001; d = .56; Monolingual: p < .001; d = 1.08). Low education group increased knowledge with bilingual (p < .001; d = .85), but not monolingual (p = .79; d = .08) modality. Bilingual modality yielded greater confidence creating a family tree (p = .03). CONCLUSIONS: Bilingual approach provides a better opportunity for lower educated Deaf ASL-users to access cancer genetics information than a monolingual approach.


Assuntos
Educação em Saúde/métodos , Conhecimentos, Atitudes e Prática em Saúde , Multilinguismo , Neoplasias/genética , Pessoas com Deficiência Auditiva , Autoeficácia , Línguas de Sinais , Acesso à Informação , Adulto , Surdez , Pessoas com Deficiência , Escolaridade , Feminino , Predisposição Genética para Doença , Humanos , Internet , Linguagem , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Fatores de Risco
10.
J Genet Couns ; 24(1): 104-16, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25030269

RESUMO

Research suggests that when healthcare providers lack cultural competence, minority groups, including the Deaf community, are adversely affected. Although most genetic counseling programs incorporate cultural competency training into their curricula, the extent and impact of Deaf awareness training is unknown. The purpose of this study is to assess Deaf awareness training of recent graduates and its impact on knowledge of deafness and Deaf culture, and attitudes toward deaf people. Genetic counselors who graduated within the past 5 years were invited to participate in an anonymous, online survey. Of the 135 respondents, 26 % reported no Deaf awareness training and 51 % reported limited training (1-2 h) conducted primarily by program instructors. Nearly one-third felt their Deaf awareness training was insufficient. Respondents lacked knowledge regarding effects of cochlear implants on residual hearing, communication between deaf children and hearing parents, and working with sign language interpreters. However, scores on knowledge of deafness and Deaf culture items and scores on attitudes toward deaf people scale did not differ significantly between respondents who had Deaf awareness training and those who did not. These findings suggest that genetic counseling students may not receive adequate Deaf awareness training. Future efforts should focus on increasing Deaf awareness in genetic counseling students, and investigating whether this change improves genetic counseling experiences for Deaf individuals.


Assuntos
Barreiras de Comunicação , Competência Cultural/organização & administração , Surdez , Aconselhamento Genético/métodos , Relações Profissional-Paciente , Adulto , Atitude do Pessoal de Saúde , Criança , Feminino , Aconselhamento Genético/psicologia , Humanos , Masculino , Línguas de Sinais
11.
Genet Med ; 17(1): 63-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24946156

RESUMO

PURPOSE: With the accelerated implementation of genomic medicine, health-care providers will depend heavily on professional guidelines and recommendations. Because genomics affects many diseases across the life span, no single professional group covers the entirety of this rapidly developing field. METHODS: To pursue a discussion of the minimal elements needed to develop evidence-based guidelines in genomics, the Centers for Disease Control and Prevention and the National Cancer Institute jointly held a workshop to engage representatives from 35 organizations with interest in genomics (13 of which make recommendations). The workshop explored methods used in evidence synthesis and guideline development and initiated a dialogue to compare these methods and to assess whether they are consistent with the Institute of Medicine report "Clinical Practice Guidelines We Can Trust." RESULTS: The participating organizations that develop guidelines or recommendations all had policies to manage guideline development and group membership, and processes to address conflicts of interests. However, there was wide variation in the reliance on external reviews, regular updating of recommendations, and use of systematic reviews to assess the strength of scientific evidence. CONCLUSION: Ongoing efforts are required to establish criteria for guideline development in genomic medicine as proposed by the Institute of Medicine.


Assuntos
Medicina Baseada em Evidências , Genômica , Guias de Prática Clínica como Assunto , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/tendências , Genômica/métodos , Genômica/tendências , Humanos
12.
PLoS One ; 9(11): e111512, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25375116

RESUMO

Using a prospective, longitudinal study design, this paper addresses the impact of genetic counseling and testing for deafness on deaf adults and the Deaf community. This study specifically evaluated the effect of genetic counseling and Connexin-26 and Connexin-30 genetic test results on participants' deaf identity and understanding of their genetic test results. Connexin-26 and Connexin-30 genetic testing was offered to participants in the context of linguistically and culturally appropriate genetic counseling. Questionnaire data collected from 209 deaf adults at four time points (baseline, immediately following pre-test genetic counseling, 1-month following genetic test result disclosure, and 6-months after result disclosure) were analyzed. Four deaf identity orientations (hearing, marginal, immersion, bicultural) were evaluated using subscales of the Deaf Identity Development Scale-Revised. We found evidence that participants understood their specific genetic test results following genetic counseling, but found no evidence of change in deaf identity based on genetic counseling or their genetic test results. This study demonstrated that culturally and linguistically appropriate genetic counseling can improve deaf clients' understanding of genetic test results, and the formation of deaf identity was not directly related to genetic counseling or Connexin-26 and Connexin-30 genetic test results.


Assuntos
Conexinas/genética , Surdez/genética , Aconselhamento Genético , Testes Genéticos , Pessoas com Deficiência Auditiva/psicologia , Adulto , Idoso , Conexina 26 , Conexina 30 , Surdez/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Autoimagem , Identificação Social
13.
JAMA ; 312(18): 1880-7, 2014 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-25326637

RESUMO

IMPORTANCE: Clinical exome sequencing (CES) is rapidly becoming a common molecular diagnostic test for individuals with rare genetic disorders. OBJECTIVE: To report on initial clinical indications for CES referrals and molecular diagnostic rates for different indications and for different test types. DESIGN, SETTING, AND PARTICIPANTS: Clinical exome sequencing was performed on 814 consecutive patients with undiagnosed, suspected genetic conditions at the University of California, Los Angeles, Clinical Genomics Center between January 2012 and August 2014. Clinical exome sequencing was conducted as trio-CES (both parents and their affected child sequenced simultaneously) to effectively detect de novo and compound heterozygous variants or as proband-CES (only the affected individual sequenced) when parental samples were not available. MAIN OUTCOMES AND MEASURES: Clinical indications for CES requests, molecular diagnostic rates of CES overall and for phenotypic subgroups, and differences in molecular diagnostic rates between trio-CES and proband-CES. RESULTS: Of the 814 cases, the overall molecular diagnosis rate was 26% (213 of 814; 95% CI, 23%-29%). The molecular diagnosis rate for trio-CES was 31% (127 of 410 cases; 95% CI, 27%-36%) and 22% (74 of 338 cases; 95% CI, 18%-27%) for proband-CES. In cases of developmental delay in children (<5 years, n = 138), the molecular diagnosis rate was 41% (45 of 109; 95% CI, 32%-51%) for trio-CES cases and 9% (2 of 23, 95% CI, 1%-28%) for proband-CES cases. The significantly higher diagnostic yield (P value = .002; odds ratio, 7.4 [95% CI, 1.6-33.1]) of trio-CES was due to the identification of de novo and compound heterozygous variants. CONCLUSIONS AND RELEVANCE: In this sample of patients with undiagnosed, suspected genetic conditions, trio-CES was associated with higher molecular diagnostic yield than proband-CES or traditional molecular diagnostic methods. Additional studies designed to validate these findings and to explore the effect of this approach on clinical and economic outcomes are warranted.


Assuntos
Exoma , Doenças Genéticas Inatas/diagnóstico , Técnicas de Diagnóstico Molecular , Doenças Raras/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Doenças Raras/genética , Análise de Sequência de DNA/métodos
15.
BMC Med Res Methodol ; 13: 145, 2013 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-24274380

RESUMO

BACKGROUND: Recruiting deaf and hard-of-hearing participants, particularly sign language-users, for genetics health service research is challenging due to communication barriers, mistrust toward genetics, and researchers' unfamiliarity with deaf people. Feelings of social exclusion and lack of social cohesion between researchers and the Deaf community are factors to consider. Social marketing is effective for recruiting hard-to-reach populations because it fosters social inclusion and cohesion by focusing on the targeted audience's needs. For the deaf population this includes recognizing their cultural and linguistic diversity, their geography, and their systems for information exchange. Here we use concepts and language from social marketing to evaluate our effectiveness to engage a U.S. deaf population in a prospective, longitudinal genetic counseling and testing study. METHODS: The study design was interpreted in terms of a social marketing mix of Product, Price, Place, and Promotion. Price addressed linguistic diversity by including a variety of communication technologies and certified interpreters to facilitate communication; Place addressed geography by including community-based participation locations; Promotion addressed information exchange by using multiple recruitment strategies. Regression analyses examined the study design's effectiveness in recruiting a culturally and linguistically diverse sample. RESULTS: 271 individuals were enrolled, with 66.1% American Sign Language (ASL)-users, 19.9% ASL + English-users, 12.6% English-users. Language was significantly associated with communication technology, participation location, and recruitment. Videophone and interpreters were more likely to be used for communication between ASL-users and researchers while voice telephone and no interpreters were preferred by English-users (Price). ASL-users were more likely to participate in community-based locations while English-users preferred medically-based locations (Place). English-users were more likely to be recruited through mass media (Promotion) while ASL-users were more likely to be recruited through community events and to respond to messaging that emphasized inclusion of a Deaf perspective. CONCLUSIONS: This study design effectively engaged the deaf population, particularly sign language-users. Results suggest that the deaf population's cultural and linguistic diversity, geography, and forms of information exchange must be taken into account in study designs for successful recruitment. A social marketing approach that incorporates critical social determinants of health provides a novel and important framework for genetics health service research targeting specific, and hard-to-reach, underserved groups.


Assuntos
Barreiras de Comunicação , Surdez/genética , Aconselhamento Genético , Seleção de Pacientes , Marketing Social , Adulto , Feminino , Testes Genéticos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Línguas de Sinais
16.
J Genet Couns ; 22(4): 492-507, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23430402

RESUMO

Limited data suggest that enhanced self-knowledge from genetic information related to non-medical traits can have a positive impact on psychological well-being. Deaf individuals undertake genetic testing for deaf genes to increase self-knowledge. Because deafness is considered a non-medical trait by many individuals, we hypothesized that deaf individuals receiving a genetic explanation for why they are deaf will experience increased psychological well-being. We report results from a prospective, longitudinal study to determine the impact of genetic testing (GJB2, Cx26; GJB6, Cx30) on perceived personal control (PPC), anxiety, and depression in deaf adults (N = 209) assessed following pre-test genetic counseling as well as 1-month and 6-months following test result disclosure. Participants were classified as Cx positive (n = 82) or Cx negative/inconclusive (n = 127). There was significant evidence for Cx group differences in PPC and anxiety over time (PPC: Cx group*time interaction p = 0.0007; anxiety: Cx group*time interaction p = 0.002), where PPC scores were significantly higher, and anxiety scores were significantly lower for the Cx positive group relative to the negative/inconclusive group following test result disclosure. Compared to pre-test, PPC scores increased at 1-month (p = 0.07) and anxiety scores decreased at 6-months (p = 0.03) for the Cx positive group. In contrast, PPC scores decreased (p = 0.009, p < 0.0001) and anxiety scores increased (p = 0.09, p = 0.02) for the Cx negative/inconclusive group at 1- and 6-months post test result disclosure. Genetic testing for deaf genes affects the psychological well-being of deaf individuals. Increasing deaf adults' access to genetic testing may potentially enhance self-knowledge and increase psychological well-being for those who receive a genetic explanation, which could offer downstream health benefits.


Assuntos
Surdez/diagnóstico , Testes Genéticos , Conexinas , Surdez/psicologia , Feminino , Humanos , Estudos Longitudinais , Estudos Prospectivos
17.
J Genet Couns ; 21(2): 256-72, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21818696

RESUMO

Empirical data on genetic counseling outcomes in the deaf population are needed to better serve this population. This study was an examination of genetics knowledge before and after culturally and linguistically appropriate pre-test genetic counseling in a diverse deaf adult sample. Individuals ≥18 years old with early-onset sensorineural deafness were offered connexin-26/30 testing and genetic counseling. Participants completed questionnaires containing 10 genetics knowledge items at baseline and following pre-test genetic counseling. The effects of genetic counseling, prior beliefs about etiology, and participant's preferred language on genetics knowledge scores were assessed (n = 244). Pre-test genetic counseling (p = .0007), language (p < .0001), prior beliefs (p < .0001), and the interaction between counseling and beliefs (p = .035) were predictors of genetics knowledge. American Sign Language (ASL)-users and participants with "non-genetic/unknown" prior beliefs had lower knowledge scores than English-users and participants with "genetic" prior beliefs, respectively. Genetics knowledge improved after genetic counseling regardless of participants' language; knowledge change was greater for the "non-genetic/unknown" beliefs group than the "genetic" beliefs group. ASL-users' lower knowledge scores are consistent with evidence that ethnic and cultural minority groups have less genetics knowledge, perhaps from exposure and access disparities. Culturally and linguistically appropriate pre-test genetic counseling significantly improved deaf individuals' genetics knowledge. Assessing deaf individuals' prior beliefs is important for enhancing genetics knowledge.


Assuntos
Surdez/genética , Testes Genéticos , Adulto , Conexina 26 , Conexina 30 , Conexinas/genética , Surdez/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Hum Hered ; 72(3): 161-72, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22004985

RESUMO

BACKGROUND AND METHODS: Association studies using unrelated individuals cannot detect intergenerational genetic effects contributing to disease. To detect these effects, we improve the extended maternal-fetal genotype (EMFG) incompatibility test to estimate any combination of maternal effects, offspring effects, and their interactions at polymorphic loci or multiple SNPs, using any size pedigrees. We explore the advantages of using extended pedigrees rather than nuclear families. We apply our methods to schizophrenia pedigrees to investigate whether the previously associated mother-daughter HLA-B matching is a genuine risk or the result of bias. RESULTS: Simulations demonstrate that using the EMFG test with extended pedigrees increases power and precision, while partitioning extended pedigrees into nuclear families can underestimate intergenerational effects. Application to actual data demonstrates that mother-daughter HLA-B matching remains a schizophrenia risk factor. Furthermore, ascertainment and mate selection biases cannot by themselves explain the observed HLA-B matching and schizophrenia association. CONCLUSIONS: Our results demonstrate the power of the EMFG test to examine intergenerational genetic effects, highlight the importance of pedigree rather than case/control or case-mother/control-mother designs, illustrate that pedigrees provide a means to examine alternative, non-causal mechanisms, and they strongly support the hypothesis that HLA-B matching is causally involved in the etiology of schizophrenia in females.


Assuntos
Predisposição Genética para Doença , Antígenos HLA-B/genética , Hereditariedade/genética , Teste de Histocompatibilidade/métodos , Esquizofrenia/genética , Alelos , Simulação por Computador , Bases de Dados Genéticas , Características da Família , Feminino , Antígenos HLA-B/imunologia , Histocompatibilidade Materno-Fetal/genética , Humanos , Funções Verossimilhança , Masculino , Modelos Genéticos , Linhagem , Fatores de Risco , Esquizofrenia/imunologia
19.
Genet Epidemiol ; 34(5): 512-21, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20552637

RESUMO

Maternal-fetal genotype (MFG) incompatibility is an interaction between the genes of a mother and offspring at a particular locus that adversely affects the developing fetus, thereby increasing susceptibility to disease. Statistical methods for examining MFG incompatibility as a disease risk factor have been developed for nuclear families. Because families collected as part of a study can be large and complex, containing multiple generations and marriage loops, we create the Extended-MFG (EMFG) Test, a model-based likelihood approach, to allow for arbitrary family structures. We modify the MFG test by replacing the nuclear-family based "mating type" approach with Ott's representation of a pedigree likelihood and calculating MFG incompatibility along with the Mendelian transmission probability. In order to allow for extension to arbitrary family structures, we make a slightly more stringent assumption of random mating with respect to the locus of interest. Simulations show that the EMFG test has appropriate type-I error rate, power, and precise parameter estimation when random mating holds. Our simulations and real data example illustrate that the chief advantages of the EMFG test over the earlier nuclear family version of the MFG test are improved accuracy of parameter estimation and power gains in the presence of missing genotypes.


Assuntos
Predisposição Genética para Doença , Modelos Genéticos , Modelos Estatísticos , Núcleo Familiar , Alelos , Simulação por Computador , Saúde da Família , Feminino , Testes Genéticos , Genótipo , Humanos , Funções Verossimilhança , Mães , Linhagem , Gravidez , Fatores de Risco
20.
J Deaf Stud Deaf Educ ; 15(3): 209-27, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20488870

RESUMO

This article examines the relationship between cultural affiliation and deaf adults' motivations for genetic testing for deafness in the first prospective, longitudinal study to examine the impact of genetic counseling and genetic testing on deaf adults and the deaf community. Participants (n = 256), classified as affiliating with hearing, Deaf, or both communities, rated interest in testing for 21 reasons covering 5 life domains. Findings suggest strong interest in testing to learn why they are deaf, but little interest in using it for decisions about a partner or having children. Culturally mediated variation was also demonstrated. Deaf and both communities groups viewed testing as useful for more life domains than the hearing community group. Deaf and both communities had similar motivations related to further exploration, understanding, or strengthening of deafness. Motivations related to "hearing" were also relevant for both communities. We conclude that cultural affiliation is an important factor for constructing motivations for genetic testing.


Assuntos
Atitude Frente a Saúde , Aconselhamento , Cultura , Surdez/genética , Testes Genéticos , Conexina 26 , Conexina 30 , Conexinas/genética , Seguimentos , Audição , Humanos , Motivação , Grupo Associado , Estudos Prospectivos , Identificação Social , Inquéritos e Questionários
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA