NBAS pathogenic variants: Defining the associated clinical and facial phenotype and genotype-phenotype correlations.
Hum Mutat
; 40(6): 721-728, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30825388
ABSTRACT
The pathogenic variants in the neuroblastoma-amplified sequence (NBAS) are associated with a clinical spectrum involving the hepatic, skeletal, ocular, and immune systems. Here, we report on two unrelated subjects with a complex phenotype solved by whole-exome sequencing, who shared a synonymous change in NBAS that was documented to affect the transcript processing and co-occurring with a truncating change. Starting from these two cases, we systematically assessed the clinical information available for all subjects with biallelic NBAS pathogenic variants (73 cases in total). We revealed a recognizable facial profile (hypotelorism, thin lips, pointed chin, and "progeroid" appearance) determined by using DeepGestalt facial recognition technology, and we provide evidence for the occurrence of genotype-phenotype correlations. Notably, severe hepatic involvement was associated with variants affecting the NBAS-Nter and Sec39 domains, whereas milder liver involvement and immunodeficiency were generally associated with variants located at the N-terminus and C-terminus of the protein. Remarkably, no patient was reported to carry two nonsense variants, suggesting lethality of complete NBAS loss-of-function.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Anormalidades Múltiplas
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Mutação Silenciosa
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Sequenciamento do Exoma
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Proteínas de Neoplasias
Tipo de estudo:
Risk_factors_studies
Limite:
Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Hum Mutat
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália