RESUMO
Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, performed at a tertiary center in Israel, over a 3-year period (2018-2020). Probands presented with (1) moderate-to-profound global developmental delay (GDD)/intellectual disability (ID); or (2) mild GDD/ID with epilepsy or congenital anomaly; and/or (3) MCA. Subjects with normal chromosomal microarray analysis who met inclusion criteria were included, totaling 280 consecutive cases. Trio ES (proband and parents) was the default option. In 252 cases (90.0%), indication of NDD was noted. Most probands were males (62.9%), and their mean age at ES submission was 9.3 years (range 1 month to 51 years). Molecular diagnosis was reached in 109 probands (38.9%), mainly due to de novo variants (91/109, 83.5%). Disease-causing variants were identified in 92 genes, 15 of which were implicated in more than a single case. Male sex, families with multiple-affected members and premature birth were significantly associated with lower ES yield (p < 0.05). Other factors, including MCA and coexistence of epilepsy, autism spectrum disorder, microcephaly or abnormal brain magnetic resonance imaging findings, were not associated with the yield. To conclude, our findings support the utility of clinical ES in a real-world setting, as part of a publicly funded genetic workup for individuals with GDD/ID and/or MCA.
Assuntos
Anormalidades Múltiplas/diagnóstico , Sequenciamento do Exoma/economia , Financiamento Governamental , Testes Genéticos/economia , Transtornos do Neurodesenvolvimento/diagnóstico , Anormalidades Múltiplas/economia , Anormalidades Múltiplas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Análise Custo-Benefício , Estudos de Viabilidade , Feminino , Aconselhamento Genético/economia , Aconselhamento Genético/métodos , Aconselhamento Genético/estatística & dados numéricos , Testes Genéticos/métodos , Testes Genéticos/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Israel , Masculino , Idade Materna , Transtornos do Neurodesenvolvimento/economia , Transtornos do Neurodesenvolvimento/genética , Idade Paterna , Gravidez , Diagnóstico Pré-Natal/economia , Diagnóstico Pré-Natal/métodos , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Centros de Atenção Terciária/economia , Centros de Atenção Terciária/estatística & dados numéricos , Sequenciamento do Exoma/estatística & dados numéricos , Adulto JovemRESUMO
Pericentric inversion of one chromosome 9 [inv(9)] is considered a polymorphic variation and is one of the most common forms of autosomal inversion diagnosed prenatally in amniocytes. Yet its clinical significance remains uncertain. Most publications suggest that this finding is insignificant. However, some articles report on abnormal ultrasonic findings in association, such as hydramnios, anhydramnios, hydroureter, hydronephrosis, encephalocele, and prune belly syndrome. Other reports suggest that inv(9) might be one of the etiologies of psychiatric disorders. The homozygote state, on the other hand, is rarely encountered. We report two cases of pericentric inversion of the two homologues of chromosome 9. Two similar cases were previously reported. One affected fetus was had intrauterine growth restriction and the other had Walker-Warburg syndrome as opposed to the normal outcome of our patients. Finally, a workup of this finding is suggested.