Novel biallelic loss-of-function variants in CEP290 cause Joubert syndrome in two siblings.
Hum Genomics
; 14(1): 26, 2020 06 29.
Article
en En
| MEDLINE
| ID: mdl-32600475
ABSTRACT
BACKGROUND:
Joubert syndrome (JS) is a rare genetic disorder, which can be defined by brain stem malformation, cerebellar vermis hypoplasia, and consequent "molar tooth sign" (MTS). JS always shares variety of phenotypes in development defects. With the development of next-generation sequencing, dozens of causative genes have been identified to JS so far. Here, we investigated two male siblings with JS and uncovered a novel pathogenesis through combined methods.RESULTS:
The siblings shared similar features of nystagmus, disorders of intellectual development, typical MTS, and abnormal morphology in fourth ventricle. Whole-exome sequencing (WES) and chromosome comparative genomic hybridization (CGH) were then performed on the proband. Strikingly, a maternal inherited nonsense variant (NM_025114.3 c.5953G>T [p.E1985*]) in CEP290 gene and a paternal inherited deletion in 12q21.32 including exons 1 to 10 of CEP290 gene were identified in the two affected siblings. We further confirmed the two variants by in vitro experiments quantitative PCR and PCR sequencing.CONCLUSIONS:
In this study, we first reported a novel causative mechanism of Joubert syndrome a copy number variation (CNV) combined with a single-nucleotide variant in CEP290 gene, which can be helpful in the genetic diagnosis of this disease.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Retina
/
Anomalías Múltiples
/
Cerebelo
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Anomalías del Ojo
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Proteínas de Ciclo Celular
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Predisposición Genética a la Enfermedad
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Proteínas del Citoesqueleto
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Enfermedades Renales Quísticas
/
Mutación con Pérdida de Función
/
Antígenos de Neoplasias
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Child
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Child, preschool
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Female
/
Humans
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Male
Idioma:
En
Revista:
Hum Genomics
Asunto de la revista:
GENETICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China