Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros

Banco de datos
Tipo del documento
Asunto de la revista
País de afiliación
Intervalo de año de publicación
1.
Hum Genet ; 142(6): 773-783, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37076692

RESUMEN

Exome sequencing (ES) has become the method of choice for diagnosing rare diseases, while the availability of short-read genome sequencing (SR-GS) in a medical setting is increasing. In addition, new sequencing technologies, such as long-read genome sequencing (LR-GS) and transcriptome sequencing, are being increasingly used. However, the contribution of these techniques compared to widely used ES is not well established, particularly in regards to the analysis of non-coding regions. In a pilot study of five probands affected by an undiagnosed neurodevelopmental disorder, we performed trio-based short-read GS and long-read GS as well as case-only peripheral blood transcriptome sequencing. We identified three new genetic diagnoses, none of which affected the coding regions. More specifically, LR-GS identified a balanced inversion in NSD1, highlighting a rare mechanism of Sotos syndrome. SR-GS identified a homozygous deep intronic variant of KLHL7 resulting in a neoexon inclusion, and a de novo mosaic intronic 22-bp deletion in KMT2D, leading to the diagnosis of Perching and Kabuki syndromes, respectively. All three variants had a significant effect on the transcriptome, which showed decreased gene expression, mono-allelic expression and splicing defects, respectively, further validating the effect of these variants. Overall, in undiagnosed patients, the combination of short and long read GS allowed the detection of cryptic variations not or barely detectable by ES, making it a highly sensitive method at the cost of more complex bioinformatics approaches. Transcriptome sequencing is a valuable complement for the functional validation of variations, particularly in the non-coding genome.


Asunto(s)
Discapacidades del Desarrollo , Exoma , Niño , Humanos , Exoma/genética , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Proyectos Piloto , Mapeo Cromosómico , Perfilación de la Expresión Génica/métodos
2.
Am J Med Genet A ; 179(11): 2257-2262, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31390136

RESUMEN

INTRODUCTION: SMG9 deficiency is an extremely rare autosomal recessive condition originally described in three patients from two families harboring homozygous truncating SMG9 variants in a context of severe syndromic developmental disorder. To our knowledge, no additional patient has been described since this first report. METHODS: We performed exome sequencing in a patient exhibiting a syndromic developmental delay and in her unaffected parents and report the phenotypic features. RESULTS: Our patient presented with a syndromic association of severe global developmental delay and diverse malformations, including cleft lip and palate, facial dysmorphic features, brain abnormalities, heart defect, growth retardation, and severe infections. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous. CONCLUSIONS: We confirm that bi-allelic truncating SMG9 variants cause a severe developmental syndrome including brain and heart malformations associated with facial dysmorphic features, severe growth and developmental delay with or without ophthalmological abnormalities, severe feeding difficulties, and life-threatening infections.


Asunto(s)
Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación , Alelos , Encéfalo/anomalías , Encéfalo/diagnóstico por imagen , Preescolar , Consanguinidad , Femenino , Estudios de Asociación Genética/métodos , Homocigoto , Humanos , Linaje , Fenotipo , Síndrome
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA