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Characterisation of deletions of the ZFHX1B region and genotype-phenotype analysis in Mowat-Wilson syndrome
  1. C Zweier1,
  2. I K Temple2,
  3. F Beemer3,
  4. E Zackai4,
  5. T Lerman-Sagie5,
  6. B Weschke6,
  7. C E Anderson7,
  8. A Rauch1
  1. 1Institute of Human Genetics, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany
  2. 2Wessex Clinical Genetics Service, Southampton University NHS Hospital Trust, Southampton, UK
  3. 3Department of Biomedical Genetics, University Medical Centre Utrecht, The Netherlands
  4. 4Clinical Genetics Center of The Children’s Hospital of Philadelphia, USA
  5. 5Metabolic Neurogenetic Clinic, E Wolfson Medical Centre, Holon, Israel
  6. 6Department of Paediatric Neurology, Charité Campus Virchow-Klinikum, Humboldt University, Berlin, Germany
  7. 7SCHC Pediatrics, Philadelphia, USA
  1. Correspondence to:
 Dr A Rauch, Institut für Humangenetik, Schwabachanlage 10, 91054 Erlangen, Germany; 

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In 1998, Mowat et al1 delineated a syndrome with Hirschsprung disease (HSCR) or severe constipation, microcephaly, mental retardation, and a distinctive facial appearance.1 Because two of the patients had a cytogenetically visible deletion of 2q22-q23,1,2 and all patients were sporadic cases, a contiguous gene syndrome or a dominant single gene disorder involving this locus were suggested.1 Two similar patients with cytogenetically balanced translocation t(2;13)(q22;q22) and t(2;11)(q22.2;q21), respectively, allowed Wakamatsu et al3 and Cacheux et al4 to narrow down the critical interval to 5 Mb and to one single gene respectively, which led both groups independently to the detection of intragenic mutations in the gene coding for Smad interacting protein-1 (formerly SIP1, now called zinc finger homeobox 1B (ZFHX1B)) in patients with so called “syndromic HSCR”. However, because HSCR is not an obligatory symptom and patients with and without HSCR can be recognised by other features, especially their distinct facial gestalt,5,6 we suggested that “Mowat-Wilson syndrome” (MWS) is a more appropriate name.6

Although the developmental ZFHX1B expression pattern fully explains the clinical spectrum observed in patients with Mowat-Wilson syndrome by haploinsufficiency of this gene alone,5,7 Wakamatsu et al3 initially stated that their deletion patient would have a more severe phenotype and therefore would have a contiguous gene syndrome. Amiel et al8 reported that the phenotype was similar in patients with “syndromic HSCR” caused by mutations and cytogenetically non-visible large scale deletions of the ZFHX1B locus, respectively, but the deletion sizes were not delineated. We therefore analysed deletion size and genotype-phenotype correlation in four new patients with cryptic deletions of the ZFHX1B locus.

Key points

  • Mowat-Wilson syndrome (MWS) is a distinct multiple congenital anomalies-mental retardation syndrome characterised by severe mental retardation, recognisable facial gestalt, pre- or postnatal …

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