RESUMO
The DEAD/DEAH box RNA helicases are a superfamily of proteins involved in the processing and transportation of RNA within the cell. A growing literature supports this family of proteins as contributing to various types of human disorders from neurodevelopmental disorders to syndromes with multiple congenital anomalies. This article presents a cohort of nine unrelated individuals with de novo missense alterations in DDX23 (Dead-Box Helicase 23). The gene is ubiquitously expressed and functions in RNA splicing, maintenance of genome stability, and the sensing of double-stranded RNA. Our cohort of patients, gathered through GeneMatcher, exhibited features including tone abnormalities, global developmental delay, facial dysmorphism, autism spectrum disorder, and seizures. Additionally, there were a variety of other findings in the skeletal, renal, ocular, and cardiac systems. The missense alterations all occurred within a highly conserved RecA-like domain of the protein, and are located within or proximal to the DEAD box sequence. The individuals presented in this article provide evidence of a syndrome related to alterations in DDX23 characterized predominantly by atypical neurodevelopment.
Assuntos
Transtorno do Espectro Autista/genética , RNA Helicases DEAD-box/genética , Deficiência Intelectual/genética , Transtornos do Neurodesenvolvimento/genética , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/fisiopatologia , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Instabilidade Genômica/genética , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/complicações , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/fisiopatologia , Masculino , Mutação de Sentido Incorreto/genética , Transtornos do Neurodesenvolvimento/complicações , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Splicing de RNA/genética , RNA de Cadeia Dupla/genética , Convulsões/complicações , Convulsões/genética , Convulsões/fisiopatologiaRESUMO
Although transitional challenges exist in many professions, no research has explicitly investigated challenges novice genetic counselors encounter as they enter the workforce. This qualitative study explored challenges genetic counselors face when transitioning from student to practicing counselor and their strategies for managing them. Fifteen novice genetic counselors (~1-2 years post-degree experience), recruited via the National Society of Genetic Counselors, participated in semi-structured phone interviews. Interview questions explored professional and personal challenges faced in their first 6 months, how challenges changed over time, strategies they used to manage these challenges, and resources they thought would have been helpful to have from the beginning. Inductive analysis of interview data yielded themes including: interpersonal challenges with colleagues (e.g. handling differences of opinion); intrapersonal challenges (e.g. lacking confidence, not feeling ready to 'go solo'); patient care challenges (e.g. being viewed as young/inexperienced); and logistical challenges (e.g. billing). Personal challenges included moving to a new location, preparing for boards, establishing a work-life balance, and factors associated with one's significant others. Strategies to address challenges included seeking support and guidance from experienced genetic counselors and peers, using peer supervision groups, and involvement in community activities. Participants recommended connecting with recent graduates through national and local programs to facilitate the transition from student to genetic counselor. Results suggest the 'transition years' pose a variety of professional and personal challenges. Support and guidance are key to evolving from student to practicing counselor. Creating venues to help novice counselors make connections with colleagues and other recent graduates may be beneficial.