Comprehensive ZEB2 gene analysis for Mowat–Wilson syndrome in a North American cohort: A suggested approach to molecular diagnostics

@article{Saunders2009ComprehensiveZG,
  title={Comprehensive ZEB2 gene analysis for Mowat–Wilson syndrome in a North American cohort: A suggested approach to molecular diagnostics},
  author={Carol J. Saunders and Weiwei Zhao and Holly H. Ardinger},
  journal={American Journal of Medical Genetics Part A},
  year={2009},
  volume={149A}
}
Mowat–Wilson syndrome is a genetic condition characterized by a recognizable facial phenotype in addition to moderate to severe cognitive disability with severe speech impairment and variable multiple congenital anomalies. The anomalies may include Hirschsprung disease, heart defects, structural eye anomalies including microphthalmia, agenesis of the corpus callosum, and urogenital anomalies. Microcephaly, seizure disorder and constipation are common. All typical cases result from… 
A Chinese Boy with Mowat–Wilson Syndrome Caused by a 10 bp Deletion in the ZEB2 Gene
TLDR
The clinical characteristics and gene mutation analysis of a Chinese boy with MWS showed that the facial features of MWS developed with time, and a novel deletion mutation of the ZEB2 gene was identified, contributing to expanding the mutation spectra of M WS.
Clinical and Molecular Spectrum of Four Patients Diagnosed with Mowat-Wilson Syndrome
TLDR
By defining 2 novel mutations in MWS that have not been previously reported in the literature, this study contributes to the molecular spectrum of MWS, while also providing a further insight for genetic counseling and demonstrates the importance of dysmorphological examination in clinical diagnosis.
A case of Mowat-Wilson syndrome caused by a truncating mutation within exon 8 of the ZEB2 gene.
TLDR
A Turkish boy who was clinically diagnosed with MWS and had his diagnosis confirmed by molecular analysis of the ZEB2 gene is described, which identified a heterozygous complex rearrangement in exon 8 of Z EB2 that caused a frameshift.
Delineation of CLINICAL PHENOTYPE with Interstitial Deletion on Chromosome 2 Including ZEB2 Gene
TLDR
A systematic evaluation is warranted in cases of multiple congenital anomalies with neonatal encephalopathy involving Mowat-Wilson syndrome, thereby helping the family understand the prognosis, management and recurrent risk for subsequent pregnancies.
A Diagnosis to Consider in Intellectual Disability
TLDR
3 novel mutations in 6 patients with Mowat-Wilson syndrome are reported to contribute to better delineation of the syndrome and help clinicians establish formal diagnostic criteria and genotype-phenotype correlations.
Fetal diagnosis of Mowat‐Wilson syndrome by whole exome sequencing
TLDR
The detection of a heterozygous de novo nonsense variant in ZEB2 by whole exome sequencing in a fetus with microphthalmia in addition to cardiac defects and typical MWS facial dysmorphism is reported.
A Novel Partial Duplication of ZEB2 and Review of ZEB2 Involvement in Mowat-Wilson Syndrome
TLDR
Chromosomal microarray identified a novel de novo 69-kb duplication containing exons 1 and 2 of the ZEB2 gene resulting in Mowat-Wilson syndrome on a 14-year-old female with a clinical diagnosis of Mow at- Wilson syndrome.
A novel nonsense mutation of ZEB2 gene in a Chinese patient with Mowat‐Wilson syndrome
TLDR
This work investigated the genetic causes of MWS in a 14‐year‐old girl who had characteristic features of M WS and found that haploinsufficiency of the ZEB2 gene causes MWS.
Pitt-Hopkins syndrome: Mental retardation, psychomotor and developmental delays with facial dysmorphism.
TLDR
The literature is reviewed and the photographs of 44 published patients from 2007 to 2012 are reviewed, attempting to delineate the Pitt-Hopkins syndrome phenotype and score the specific dysmorphism than help to achieve the early clinical diagnosis.
Mowat-Wilson syndrome 1 예 Delayed Diagnosis of Atypical Mowat-Wilson Syndrome
TLDR
A 7-yr-old boy with MWS with a heterozygous deletion of ZEB2 is described, which is a rare autosomal dominant developmental disorder characterized by mental retardation, delayed motor development, and a broad spectrum of clinically heterogeneous features.
...
...

References

SHOWING 1-10 OF 22 REFERENCES
ZFHX1B mutations in patients with Mowat‐Wilson syndrome
TLDR
40 novel mutations are described, suggesting that haploinsufficiency is the basis of MWS pathology, and the various mutational reports published since the identification of the causative gene are summarized.
Clinical and mutational spectrum of Mowat-Wilson syndrome.
Clinical and molecular analysis of Mowat-Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22–q24.1
TLDR
ZFHX1B clearly plays a critical role in the manifestation of clinical features of Mowat-Wilson syndrome, and the clinical features and underlying molecular basis of 27 cases with mutations or deletions in ZFHx1B are characterized.
Clinical features and management issues in Mowat–Wilson syndrome
TLDR
Clinical experience with 12 patients diagnosed with MWS within a 2‐year period of time in the United States is reported, with particular emphasis on clinical characteristics and management strategies.
Recurrence of Mowat–Wilson syndrome in siblings with the same proven mutation
TLDR
A brother and sister are described with clinical features of MWS, where both have the same truncating mutation in exon 8 of ZFHX1B, and the most likely explanation is germ‐line mosaicism.
A missense mutation in the ZFHX1B gene associated with an atypical Mowat–Wilson syndrome phenotype
TLDR
Clinical findings in a 2½‐year‐old boy with some aspects out of the MWS‐spectrum in addition to unusual anomalies and a novel missense mutation in the ZFHX1B gene are reported on.
Characterisation of deletions of the ZFHX1B region and genotype-phenotype analysis in Mowat-Wilson syndrome
TLDR
Analysis of deletion size and genotype-phenotype correlation in four new patients with cryptic deletions of the ZFHX1B locus suggested that “Mowat-Wilson syndrome” (MWS) is a more appropriate name.
Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B
TLDR
It is emphasized that this syndrome can be recognized by the facial phenotype in the absence of either HSCR or other congenital anomalies, and needs to be considered in the differential diagnosis of dysmorphism with severe mental retardation +/− epilepsy.
Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: delineation of a new syndrome and identification of a locus at chromosome 2q22-q23.
TLDR
Patients with a distinctive facial phenotype in association with mental retardation (MR), microcephaly, and short stature appear to have a separate disorder from Goldberg-Shprintzen syndrome, for which autosomal recessive inheritance has been proposed because of sib recurrence and consanguinity in some families.
Large-scale deletions and SMADIP1 truncating mutations in syndromic Hirschsprung disease with involvement of midline structures.
TLDR
SMADIP1, which encodes a transcriptional corepressor of Smad target genes, may play a role not only in the patterning of neural-crest-derived cells and of CNS but also in the development of midline structures in humans.
...
...