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2.
Genet Med ; 21(6): 1295-1307, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30349098

RESUMO

PURPOSE: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin-Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. METHODS: Clinicians entered clinical data in an extensive web-based survey. RESULTS: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. CONCLUSION: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Anormalidades Múltiplas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Proteínas Cromossômicas não Histona/genética , Exoma , Face/anormalidades , Feminino , Estudos de Associação Genética/métodos , Variação Genética/genética , Deformidades Congênitas da Mão/genética , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/genética , Masculino , Micrognatismo/genética , Pessoa de Meia-Idade , Mutação , Pescoço/anormalidades , Penetrância
3.
Hum Mol Genet ; 23(10): 2752-68, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24381304

RESUMO

Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3' terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3'-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3' end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtornos Globais do Desenvolvimento Infantil/genética , Glicoproteínas/genética , Proteínas do Tecido Nervoso/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Cromossomos Humanos Par 9 , Variações do Número de Cópias de DNA , Éxons , Feminino , Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Glicoproteínas/metabolismo , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas do Tecido Nervoso/metabolismo , Especificidade de Órgãos , Fenótipo , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Fatores de Risco , Deleção de Sequência , Fatores de Transcrição/metabolismo , Sítio de Iniciação de Transcrição , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Adulto Jovem
4.
J Adv Nurs ; 67(2): 394-400, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20955186

RESUMO

AIM: This paper is a report of a study of the effects of communication-skills training for healthcare professionals on parents' perceptions of information, care and continuity. BACKGROUND: As training in communication skills has been more and more integrated into clinical practice it has been subject to an increasing number of studies. However, the majority of studies have been conducted in outpatient clinics, have only targeted physicians, and have not been evaluated from the perspective of patients. METHOD: This intervention study, conducted from 2005 to 2007, was performed to investigate the effect of a 3-day communication course offered to all healthcare professionals in a department of paediatrics. In a pre-/post-test design, the effect of the intervention was evaluated by the parents using electronic questionnaires filled in on touch-screen computers located centrally in the wards. RESULTS: A total of 895 parents answered the questionnaires before the course (80%) and 1937 answered after the course (72%). For the questions on care and continuity, the proportion of satisfied parents increased statistically significantly for 4 out of 13 questions, e.g. Did you feel that the staff understood you situation? and Did you find that the information given by the different nurses was consistent? For the information questions, no statistically significant differences were found. CONCLUSION: It is possible to incorporate key communication skills into clinical practice by targeting all healthcare professionals. Communication skills training using interactive methods such as role-play and feedback on video recordings is recommended.


Assuntos
Comunicação , Comportamento do Consumidor/estatística & dados numéricos , Pessoal de Saúde/educação , Pais , Pediatria/normas , Relações Profissional-Família , Adolescente , Atitude do Pessoal de Saúde , Criança , Continuidade da Assistência ao Paciente/normas , Humanos , Pediatria/educação , Inquéritos e Questionários , Gravação em Vídeo
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