Phenotypic spectrum and genetics of PAX2-related disorder in the Chinese cohort.
BMC Med Genomics
; 14(1): 250, 2021 10 25.
Article
em En
| MEDLINE
| ID: mdl-34696790
ABSTRACT
BACKGROUND:
Pathogenic variants of PAX2 cause autosomal-dominant PAX2-related disorder, which includes variable phenotypes ranging from renal coloboma syndrome (RCS), congenital anomalies of the kidney and urinary tract (CAKUT) to nephrosis. Phenotypic variability makes it difficult to define the phenotypic spectrum associated with genotype.METHODS:
We collected the phenotypes in patients enrolled in the China national multicenter registry who were diagnosed with pathogenic variant in PAX2 and reviewed all published cases with PAX2-related disorders. We conducted a phenotype-based cluster analysis by variant types and molecular modeling of the structural impact of missense variants.RESULTS:
Twenty different PAX2 pathogenic variants were identified in 32 individuals (27 families) with a diagnosis of RCS (9), CAKUT (11) and nephrosis (12) from the Chinese cohort. Individuals with abnormal kidney structure (RCS or CAKUT group) tended to have likely/presumed gene disruptive (LGD) variants (Fisher test, p < 0.05). A system review of 234 reported cases to date indicated a clear association of RCS to heterozygous loss-of-function PAX2 variants (LGD variants). Furthermore, we identified a subset of PAX2 missense variants in DNA-binding domain predicted to affect the protein structure or protein-DNA interaction associated with the phenotype of RCS.CONCLUSION:
Defining the phenotypic spectrum combined with genotype in PAX2-related disorder allows us to predict the pathogenic variants associated with renal and ophthalmological development. It highlighted the approach of structure-based analysis can be applied to diagnostic strategy aiding precise and timely diagnosis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
/
Doenças Urológicas
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Anormalidades Múltiplas
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Fator de Transcrição PAX2
Tipo de estudo:
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
BMC Med Genomics
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
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GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
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UK
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UNITED KINGDOM