RESUMO
Worldwide, there are large inequalities in genetic service delivery. In 2011, we established a bi-annual joint pediatric-genetics clinic with a visiting clinical geneticist in the Dutch Caribbean. This retrospective study evaluates the yield of diagnostic testing and the clinical utility of a diagnosis for patients with rare diseases on these relatively isolated, resource-limited islands. A total of 331 patients that were referred to the clinical geneticist between November 2011 and November 2019 and had genetic testing were included in this study. A total of 508 genetic tests were performed on these patients. Microarray, next-generation sequencing gene panels, and single-gene analyses were the most frequently performed genetic tests. A molecularly confirmed diagnosis was established in 33% of patients (n = 108). Most diagnosed patients had single nucleotide variants or small insertions and/or deletions (48%) or copy number variants (34%). Molecular diagnostic yield was highest in patients referred for seizures and developmental delay/intellectual disability. The genetic diagnosis had an impact on clinical management in 52% of patients. Referrals to other health professionals and changes in therapy were the most frequently reported clinical consequences. In conclusion, despite limited financial resources, our genetics service resulted in a reasonably high molecular diagnostic yield. Even in this resource-limited setting, a genetic diagnosis had an impact on clinical management for the majority of patients. Our approach with a visiting clinical geneticist may be an example for others who are developing genetic services in similar settings.
Assuntos
Variações do Número de Cópias de DNA , Deficiência Intelectual , Região do Caribe/epidemiologia , Criança , Testes Genéticos/métodos , Humanos , Deficiência Intelectual/genética , Estudos RetrospectivosRESUMO
Pathogenic variants in components of the minor spliceosome have been associated with several human diseases. Recently, it was reported that biallelic RNPC3 variants lead to severe isolated growth hormone deficiency and pituitary hypoplasia. The RNPC3 gene codes for the U11/U12-65K protein, a component of the minor spliceosome. The minor spliceosome plays a role in the splicing of minor (U12-type) introns, which are present in ~700-800 genes in humans and represent about 0.35% of all introns. Here, we report a second family with biallelic RNPC3 variants in three siblings with a growth hormone deficiency, central congenital hypothyroidism, congenital cataract, developmental delay/intellectual deficiency and delayed puberty. These cases further confirm the association between biallelic RNPC3 variants and severe postnatal growth retardation due to growth hormone deficiency. Furthermore, these cases show that the phenotype of this minor spliceosome-related disease might be broader than previously described.
Assuntos
Hipotireoidismo Congênito/genética , Deficiências do Desenvolvimento/genética , Nanismo Hipofisário/genética , Proteínas Nucleares/genética , Proteínas de Ligação a RNA/genética , Adolescente , Adulto , Catarata , Criança , Pré-Escolar , Hipotireoidismo Congênito/complicações , Hipotireoidismo Congênito/patologia , Deficiências do Desenvolvimento/complicações , Deficiências do Desenvolvimento/patologia , Nanismo Hipofisário/complicações , Nanismo Hipofisário/diagnóstico , Nanismo Hipofisário/patologia , Feminino , Hormônio do Crescimento/deficiência , Hormônio do Crescimento/genética , Humanos , Íntrons/genética , Masculino , Fenótipo , Puberdade Tardia/complicações , Puberdade Tardia/genética , Puberdade Tardia/patologia , Splicing de RNA/genética , Spliceossomos/genética , Spliceossomos/patologia , Adulto JovemRESUMO
Research on the perspectives of patients and parents regarding genetic testing and its implications has been performed mostly in Europe, Canada, the United States, Australia and New Zealand, even though genetic testing is becoming increasingly available worldwide. We aimed to fill this knowledge gap by exploring the experiences and needs of parents in the Dutch Caribbean who received a genetic diagnosis for the rare disease of their child. We conducted 23 semi-structured interviews with 30 parents of children diagnosed with various rare genetic diseases in Aruba, Bonaire and Curaçao (ABC-islands). Two researchers independently analyzed the interviews using a thematic approach. Main themes identified were: (1) getting a genetic diagnosis, (2) coping, support and perceived social stigma, (3) living on a small island, and (4) needs regarding genetic services. Our results indicate that, despite reported limitations regarding the availability of healthcare and support services, receiving a genetic diagnosis for their child was valuable for most participants. While some of the participants' experiences with and attitudes towards the genetic diagnosis of their child were similar to those reported in previous studies, we identified a number of aspects that are more specifically related to this Dutch Caribbean setting. These include coping through faith and religion, social stigma and being the only one on the island with a specific genetic disorder. The results of this study and the provided recommendations may be useful when developing genetic testing and counseling services in similar settings.