RESUMO
Although whole-exome sequencing (WES) is the gold standard for the diagnosis of neurodevelopmental disorders (NDDs), it remains expensive for some genetic centers. Commercialized panels comprising all OMIM-referenced genes called "medical exome" (ME) constitute an alternative strategy to WES, but its efficiency is poorly known. In this study, we report the experience of 2 clinical genetic centers using ME for diagnosis of NDDs. We recruited 216 consecutive index patients with NDDs in 2 French genetic centers, corresponded to the daily practice of the units and included non-syndromic intellectual disability (NSID, n = 33), syndromic ID (NSID = 122), pediatric neurodegenerative disorders (n = 7) and autism spectrum disorder (ASD, n = 54). We sequenced samples from probands and their parents (when available) with the Illumina TruSight One sequencing kit. We found pathogenic or likely pathogenic variants in 56 index patients, for a global diagnostic yield of 25.9%. The diagnosis yield was higher in patients with ID as the main diagnosis (32%) than in patients with ASD (3.7%). Our results suggest that the use of ME is a valuable strategy for patients with ID when WES cannot be used as a routine diagnosis tool.
Assuntos
Sequenciamento do Exoma , Estudos de Associação Genética , Predisposição Genética para Doença , Transtornos do Neurodesenvolvimento/genética , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Biologia Computacional/métodos , Feminino , Estudos de Associação Genética/métodos , Humanos , Lactente , Padrões de Herança , Masculino , Pessoa de Meia-Idade , Transtornos do Neurodesenvolvimento/diagnóstico , Fenótipo , Análise de Sequência de DNA/métodos , Adulto JovemRESUMO
OBJECTIVE: To determine if there exists a significant association between prenatally detected left ventricular echogenic foci and chromosomal abnormalities. METHODS: Over a 10-month period the presence of intracardiac echogenic foci was recorded on all low-risk patients referred for anatomical assessment. The study group consisted of 113 singleton fetuses and was compared to a control group with no foci. RESULTS: Among the study group with echogenic foci, 5 chromosomal abnormalities (three trisomies) were detected. In the control group only one chromosomal abnormality was diagnosed. CONCLUSION: An association exists between the finding of intracardiac echogenic foci in the fetus and the presence of chromosomal abnormalities.
Assuntos
Aberrações Cromossômicas , Ecocardiografia , Coração/embriologia , Ultrassonografia Pré-Natal , Adulto , Feminino , Idade Gestacional , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/embriologia , Humanos , Cariotipagem , Gravidez , Fatores de Risco , TrissomiaRESUMO
The aim of this study was to determine if vitamin A supplementation reduces the incidence of bacterial infections among elderly nursing-home residents. One hundred and nine patients were enrolled into a double-masked, placebo-controlled trial at an academically affiliated nursing home. Fifty-six patients received a single capsule containing 1,000 IU of vitamin A (placebo) and 53 received a single capsule containing 200,000 IU of vitamin A. Antibiotic-treated infections were enumerated for 90 days after dosing and infection rates were expressed per 1000 days of follow-up. There were 42 antibiotic-treated infections altogether, 21 in each group. The infection rates in the vitamin A and placebo groups were 4.7 and 4.3 per 1,000 days of follow-up, respectively (relative risk 1.1; 95% CI 0.6, 2.0). The findings of this study do not support a role for vitamin A supplements for the prevention of infections among frail elderly nursing-home patients.
