Targeted gene/syndrome under study:

ZEB2 (OMIM *605802) / Mowat-Wilson Syndrome (OMIM #235730)


Recently we defined a robust DNA methylation (DNAm) signature for Mowat-Wilson Syndrome (MOWS, caused by haploinsufficiency of ZEB2). This DNAm signature is a useful tool for early diagnosis, with the potential to classify ZEB2 missense variants of uncertain significance (VUS) as well.

In a further collaborative effort involving national and international groups, we propose to extend the utilization of DNAm profiling to individuals with:

1. suspected MOWS or MOWS-like disorder and a VUS in ZEB2 (e.g. missense and noncoding variants, C-ter truncation);

2. typical MOWS clinical presentation, but no ZEB2 gene/locus alteration detected after appropriate testing (ZEB2 sequencing + MLPA, or equivalent NGS).

We propose to collect DNA samples from peripheral blood and record clinical data of such individuals, in order to help define their diagnosis and to investigate epigenetic correlations between typical and atypical forms of MOWS.

Coordinating clinicians

Dr. Livia Garavelli –

Dr. Stefano Caraffi –


Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy

Specific requirements beyond clinical data and genotype data sharing:

1- Re-analysis of DNA samples: Yes

2- Resampling of patients: No 

3- Linked to a translational/basic research project: No