Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease

Wakamatsu, Nobuaki; Yamada, Yasukazu; Yamada, Kenichiro; Ono, Takao; Nomura, Noriko; Taniguchi, Hiroko; Kitoh, Hiroshi; Mutoh, Norihiro; Yamanaka, Tsutomu; Mushiake, Kyosuke; Kato, Kanefusa; Sonta, Shin-ichi; Nagaya, Masahiro

doi:10.1038/86860

Cited by 301 publications

(244 citation statements)

References 12 publications

Supporting

Mentioning

233

Contrasting

Unclassified

Order By: Relevance

“…The causative genetic defect was mapped to chromosome 2q21-q23 based on cytogenetic deletions in two patients, 1,2 and narrowed to heterozygous mutations of the ZEB2 gene by subsequent reports. 3,4 In 2002 Zweier et al 5 further delineated the phenotype of MWS with or without HSCR, invariably characterized by ZEB2 gene defects, and proposed that the condition be named Mowat-Wilson syndrome. More than 300 patients have been reported so far [6][7][8][9][10][11][12][13][14][15][16][17] (additional reviewed articles are listed in Supplementary File S1 online).…”

Section: Mowat-wilson Syndrome (Mws) (Omim # 235730) Ismentioning

confidence: 99%

Phenotype and genotype of 87 patients with Mowat–Wilson syndrome and recommendations for care

Ivanovski

Djurić

Caraffi

et al. 2018

Genetics in Medicine

131

View full text Add to dashboard Cite

ORIGINAL RESEARCH ARTICLEPurpose: Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS. Methods:In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.Results: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations. Conclusion:Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.

show abstract

Section: Mowat-wilson Syndrome (Mws) (Omim # 235730) Ismentioning

confidence: 99%

Phenotype and genotype of 87 patients with Mowat–Wilson syndrome and recommendations for care

Ivanovski

Djurić

Caraffi

et al. 2018

Genetics in Medicine

131

View full text Add to dashboard Cite

show abstract

“…While ZEB1 and ZEB2 have many similar properties in transcriptional regulation, they are different in their expression profiles, some molecular and biological functions, including regulation of cell differentiation and disease progression (Postigo and Dean, 2000; Wakamatsu et al ., 2001). Epithelial cells lose their adhesive property and become migratory and invasive as they become mesenchymal cells during the EMT process (Nieto et al ., 2016; Thiery et al ., 2009).…”

Section: Introductionmentioning

confidence: 99%

ZEB1‐regulated inflammatory phenotype in breast cancer cells

et al. 2017

View full text Add to dashboard Cite

Zinc finger E‐box binding protein 1 (ZEB1) and ZEB2 induce epithelial‐mesenchymal transition (EMT) and enhance cancer progression. However, the global view of transcriptional regulation by ZEB1 and ZEB2 is yet to be elucidated. Here, we identified a ZEB1‐regulated inflammatory phenotype in breast cancer cells using chromatin immunoprecipitation sequencing and RNA sequencing, followed by gene set enrichment analysis (GSEA) of ZEB1‐bound genes. Knockdown of ZEB1 and/or ZEB2 resulted in the downregulation of genes encoding inflammatory cytokines related to poor prognosis in patients with cancer, including IL6 and IL8, therefore suggesting that ZEB1 and ZEB2 have similar functions in terms of the regulation of production of inflammatory cytokines. Antibody array and ELISA experiments confirmed that ZEB1 controlled the production of the IL‐6 and IL‐8 proteins. The secretory proteins regulated by ZEB1 enhanced breast cancer cell proliferation and tumor growth. ZEB1 expression in breast cancer cells also affected the growth of fibroblasts in cell culture, and the accumulation of myeloid‐derived suppressor cells in tumors in vivo. These findings provide insight into the role of ZEB1 in the progression of cancer, mediated by inflammatory cytokines, along with the initiation of EMT.

show abstract

“…In this study, two related Zfhx1 transcription factors in mouse encoded by Zfhx1a (␦EF1) (Funahashi et al, 1993) and Zfhx1b (Sip1) (Verschuren et al, 1999;Zeb2, Postigo and Dean, 2000) genes (the Zfhx1 gene family) were investigated. Zfhx1 genes, named after Drosophila Zfh1 (Fortini et al, 1991), are conserved among animal species from nematode to higher vertebrates (Genetta and Kadesch, 1996;Sekido et al, 1996;Wakamatsu et al, 2001;Papin et al, 2002, Wacker et al, 2003Nitta et al, 2004), indicating an evolutionarily conserved important regulatory function. Protein factors in this family are characterized by the possession of a pair of similar zinc finger clusters near the N-and C-termini, and a homeodomain in the middle.…”

Section: Introductionmentioning

confidence: 99%

Complementary expression pattern of Zfhx1 genes Sip1 and δEF1 in the mouse embryo and their genetic interaction revealed by compound mutants

Miyoshi

Maruhashi

Putte

et al. 2006

Developmental Dynamics

View full text Add to dashboard Cite

In mouse embryos, the Zfhx1 transcription factor genes, Sip1 and ␦EF1, are expressed in complementary domains in many tissues. Their possible synergism in embryogenesis was investigated by comparing the phenotype of Sip1؊/؊;␦EF1؊/؊ double homozygotes with single homozygous embryos. Unexpectedly, in Sip1؊/؊ embryos ␦EF1 was ectopically activated, suggesting a negative regulation of ␦EF1 expression by Sip1. Sip1؊/؊;␦EF1؊/؊ embryos were similar to Sip1؊/؊ embryos in short somite production and developmental arrest around E8.5, but showed more severe defects in dorsal neural tube morphogenesis accompanied by a larger reduction of Sox2 expression, ascribable to the loss of the ectopic ␦EF1 expression. Sip1؉/؊;␦EF1؊/؊ embryos develop various morphological defects after E10 that were absent in ␦EF1؊/؊ embryos even in tissues without significant overlap of Sip1 and ␦EF1 expression, and arrested during mid gestation earlier than ␦EF1؊/؊ embryos. These findings indicate that complex synergistic interactions occur between Zfhx1 transcription factor genes during mouse embryogenesis. Developmental Dynamics 235: 1941-1952, 2006.

show abstract

Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease

Cited by 301 publications

References 12 publications

Phenotype and genotype of 87 patients with Mowat–Wilson syndrome and recommendations for care

Phenotype and genotype of 87 patients with Mowat–Wilson syndrome and recommendations for care

ZEB1‐regulated inflammatory phenotype in breast cancer cells

Complementary expression pattern of Zfhx1 genes Sip1 and δEF1 in the mouse embryo and their genetic interaction revealed by compound mutants

Contact Info

Product

Resources

About