CytoCell Saethre-Chotzen/Williams-Beuren Combination

Probe specification

• TWIST1, 7p21.1, Red
• WBSCR, 7q11.23, Green

The TWIST1 probe is 179kb, labelled in red and covers a region including the entire TWIST1 gene and flanking DNA. The Williams-Beuren region probe, labelled in green, consists of three non-overlapping clones (148kb, 144kb and 204kb), which cover much of the deletion region.

Probe information

Saethre-Chotzen syndrome is a rare, congenital, autosomal dominant disorder characterised by craniofacial and limb abnormalities¹.

The incidence of this syndrome is estimated to be 1 in 25,000-50,000 live births, though due to the phenotype often being very mild, it is possible that the syndrome is under diagnosed¹. The identification of TWIST1 (a basic helix-loop-helix transcription factor on chromosome band 7p21.1) as a causative gene^2,3 has proved invaluable for the diagnosis of this phenotypically variable disorder¹.

Williams-Beuren Syndrome (WBS) is a rare neurodevelopmental disorder caused by a deletion (approx. 1.5-1.8Mb in size, containing around 28 genes⁶) within chromosome band 7q11.23⁴. The incidence of this syndrome is estimated at 1 in 7,500 to 20,000 live births^5,6.

Patients display a distinctive ‘elfin’ facial appearance, connective tissue problems, SupravalVular Aortic Stenosis (SVAS), growth retardation, renal anomalies, transient hypercalcaemia, hyperacusis and mental retardation⁷. Haploinsufficiency or hemizygosity of the elastin (ELN) gene has been identified as being responsible for the SVAS^8,9 but none of the other clinical features of the syndrome have been unequivocally attributed to specific genes within the WBS deleted region. These genotype-phenotype correlations are made more difficult in WBS patients as the deletion has also been shown to have an effect on normal copy number genes that neighbour the deletion breakpoints¹⁰.

The Saethre-Chotzen/Williams-Beuren Combination contains a red probe that covers the TWIST1 gene for Saethre-Chotzen syndrome and a green probe covering the area around the ELN gene in the Williams-Beuren syndrome deleted region.