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Phenotypic spectrum and genetics of PAX2-related disorder in the Chinese cohort.
Yang, Xue; Li, Yaqi; Fang, Ye; Shi, Hua; Xiang, Tianchao; Liu, Jiaojiao; Liu, Jialu; Tang, Xiaoshan; Fang, Xiaoyan; Chen, Jing; Zhai, Yihui; Shen, Qian; Bi, Yunli; Qian, Yanyan; Wu, Bingbing; Wang, Huijun; Zhou, Wenhao; Ma, Duan; Bai, Haitao; Mao, Jianhua; Chen, Lizhi; Wang, Xiaowen; Gao, Xiaojie; Zhang, Ruifeng; Zhuang, Jieqiu; Zhang, Aihua; Jiang, Xiaoyun; Xu, Hong; Rao, Jia.
Afiliação
  • Yang X; Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of CHINA, 399 Wanyuan Road, Shanghai, China.
  • Li Y; Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
  • Fang Y; Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, 201102, China.
  • Shi H; Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of CHINA, 399 Wanyuan Road, Shanghai, China.
  • Xiang T; Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
  • Liu J; Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, 201102, China.
  • Liu J; Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of CHINA, 399 Wanyuan Road, Shanghai, China.
  • Tang X; Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
  • Fang X; Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, 201102, China.
  • Chen J; Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of CHINA, 399 Wanyuan Road, Shanghai, China.
  • Zhai Y; Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
  • Shen Q; Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, 201102, China.
  • Bi Y; Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of CHINA, 399 Wanyuan Road, Shanghai, China.
  • Qian Y; Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
  • Wu B; Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, 201102, China.
  • Wang H; Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of CHINA, 399 Wanyuan Road, Shanghai, China.
  • Zhou W; Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
  • Ma D; Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, 201102, China.
  • Bai H; Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of CHINA, 399 Wanyuan Road, Shanghai, China.
  • Mao J; Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
  • Chen L; Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, 201102, China.
  • Wang X; Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of CHINA, 399 Wanyuan Road, Shanghai, China.
  • Gao X; Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
  • Zhang R; Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, 201102, China.
  • Zhuang J; Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of CHINA, 399 Wanyuan Road, Shanghai, China.
  • Zhang A; Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
  • Jiang X; Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, 201102, China.
  • Xu H; Department of Nephrology, Children's Hospital of Fudan University, National Pediatric Medical Center of CHINA, 399 Wanyuan Road, Shanghai, China.
  • Rao J; Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenótipo / Doenças Urológicas / Anormalidades Múltiplas / Fator de Transcrição PAX2 Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / 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 / GREAT BRITAIN / INGLATERRA / REINO UNIDO / SCOTLAND / UK / UNITED KINGDOM

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenótipo / Doenças Urológicas / Anormalidades Múltiplas / Fator de Transcrição PAX2 Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / 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 / GREAT BRITAIN / INGLATERRA / REINO UNIDO / SCOTLAND / UK / UNITED KINGDOM