Lowry-Wood syndrome: further evidence of association with RNU4ATAC, and correlation between genotype and phenotype.
Hum Genet
; 137(11-12): 905-909, 2018 Dec.
Article
em En
| MEDLINE
| ID: mdl-30368667
ABSTRACT
Lowry-Wood syndrome (LWS) is a skeletal dysplasia characterized by multiple epiphyseal dysplasia associated with microcephaly, developmental delay and intellectual disability, and eye involvement. Pathogenic variants in RNU4ATAC, an RNA of the minor spliceosome important for the excision of U12-dependent introns, have been recently associated with LWS. This gene had previously also been associated with microcephalic osteodysplastic primordial dwarfism (MOPD) and Roifman syndrome (RS), two distinct conditions which share with LWS some skeletal and neurological anomalies. We performed exome sequencing in two individuals with Lowry-Wood syndrome. We report RNU4ATAC pathogenic variants in two further patients. Moreover, an analysis of all RNU4ATAC variants reported so far showed that FitCons scores for nucleotides mutated in the more severe MOPD are higher than RS or LWS and that they were more frequently located in the 5' Stem-Loop of the RNA critical for the formation of the U4/U6.U5 tri-snRNP complex, whereas the variants are more dispersed in the other conditions. We are thus confirming that RNU4ATAC is the gene responsible for LWS and provide a genotype-phenotype correlation analysis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteocondrodisplasias
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RNA Nuclear Pequeno
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Predisposição Genética para Doença
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Transtornos do Crescimento
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Deficiência Intelectual
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Microcefalia
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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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 Genet
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Canadá