Genitourinary Anomalies in Mowat-Wilson Syndrome with Deletion/Mutation in the Zinc Finger Homeo Box 1B Gene (ZFHX1B)

Garavelli, Livia; Cerruti-Mainardi, P.; Virdis, R; Pedori, S.; Pastore, Guido; Godi, Michela; Provera, S.; Rauch, Anita; Zweier, Christiane; Zollino, Marcella; Banchini, G; Longo, Nicola; Mowat, David; Neri, Giovanni; Bernasconi, Sergio

doi:10.1159/000085894

Cited by 16 publications

(9 citation statements)

References 44 publications

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“…None of these three ZNFs have been previously associated with the development of HS. However, two other zinc finger box genes, ZEB1 and ZEB2, have been associated with HS [20], [29]. Our data indicate that ZFP-mediated transcriptional activity might be required for the effect of BPA on human reproduction.…”

Section: Discussionmentioning

confidence: 74%

Identification of Novel Low-Dose Bisphenol A Targets in Human Foreskin Fibroblast Cells Derived from Hypospadias Patients

et al. 2012

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Background/PurposeThe effect of low-dose bisphenol A (BPA) exposure on human reproductive health is still controversial. To better understand the molecular basis of the effect of BPA on human reproductive health, a genome-wide screen was performed using human foreskin fibroblast cells (hFFCs) derived from child hypospadias (HS) patients to identify novel targets of low-dose BPA exposure.Methodology/Principal FindingsGene expression profiles of hFFCs were measured after exposure to 10 nM BPA, 0.01 nM 17β-estradiol (E2) or 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 24 h. Differentially expressed genes were identified using an unpaired Student's t test with P value cut off at 0.05 and fold change of more than 1.2. These genes were selected for network generation and pathway analysis using Ingenuity Pathways Analysis, Pathway Express and KegArray. Seventy-one genes (42 downregulated and 29 upregulated) were identified as significantly differentially expressed in response to BPA, among which 43 genes were found to be affected exclusively by BPA compared with E2 and TCDD. Of particular interest, real-time PCR analysis revealed that the expression of matrix metallopeptidase 11 (MMP11), a well-known effector of development and normal physiology, was found to be inhibited by BPA (0.47-fold and 0.37-fold at 10 nM and 100 nM, respectively). Furthermore, study of hFFCs derived from HS and cryptorchidism (CO) patients (n = 23 and 11, respectively) indicated that MMP11 expression was significantly lower in the HS group than in the CO group (0.25-fold, P = 0.0027).Conclusions/SignificanceThis present study suggests that an involvement of BPA in the etiology of HS might be associated with the downregulation of MMP11. Further study to elucidate the function of the novel target genes identified in this study during genital tubercle development might increase our knowledge of the effects of low-dose BPA exposure on human reproductive health.

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Section: Discussionmentioning

confidence: 74%

Identification of Novel Low-Dose Bisphenol A Targets in Human Foreskin Fibroblast Cells Derived from Hypospadias Patients

et al. 2012

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“…[2] Patients can present a variety of other anomalies, such as short stature (50%); microcephaly (84%); HSCR (50%); chronic constipation (25%); malformations of the brain, particularly agenesis of the corpus callosum (60%); seizures (75%), with no predilection for any particular seizure type; congenital heart defects (75%); and urogenital anomalies,[245] particularly hypospadias (55%). [26] In our patient, suspicion of MWS was based essentially on the dysmorphic features associated with severe mental retardation and seizures. Absence of microcephaly, HSCR, congenital heart defect, and hypospadias did not preclude the diagnosis.…”

Section: Discussionmentioning

confidence: 95%

Mowat-Wilson syndrome in a Moroccan consanguineous family

et al. 2007

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Mowat-Wilson syndrome is a mental retardation-multiple congenital anomaly syndrome characterized by a typical facies, developmental delay, epilepsy, and variable congenital malformations, including Hirschsprung disease, urogenital anomalies, congenital heart disease, and agenesis of the corpus callosum. This disorder is sporadic and is caused by heterozygous mutations or deletions of the ZFHX1B gene located in the 2q22 region. We report here the first Moroccan patient, born to consanguineous parents, with Mowat-Wilson syndrome, due to a de novo, unreported mutation of the ZFHX1B gene.

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“…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

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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.

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Genitourinary Anomalies in Mowat-Wilson Syndrome with Deletion/Mutation in the Zinc Finger Homeo Box 1B Gene (ZFHX1B)

Cited by 16 publications

References 44 publications

Identification of Novel Low-Dose Bisphenol A Targets in Human Foreskin Fibroblast Cells Derived from Hypospadias Patients

Identification of Novel Low-Dose Bisphenol A Targets in Human Foreskin Fibroblast Cells Derived from Hypospadias Patients

Mowat-Wilson syndrome in a Moroccan consanguineous family

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

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