177 VPS33B mutations cause ARKID syndrome affecting Rab protein interaction, collagen modification and epidermal structure

Three Austrian patients presented with severe palmoplantar keratoderma associated with ichthyosis and sensorineural deafness. Exome sequencing revealed biallelic mutations in VPS33B, encoding VPS33B, a Sec1/Munc18 family protein which interacts with Rab11a and Rab25 proteins and is involved in trafficking of the collagen modifying enzyme LH3. Two patients showed the homozygous missense variant p.Gly131Glu, whilst one patient was compound heterozygous for p.Gly131Glu and the splice site mutation c.240-1G>C, previously reported in patients with arthrogryposis renal dysfunction and cholestasis syndrome.

Source: Journal of Investigative Dermatology - September 8, 2017 Category: Dermatology Authors: R. Gruber, C. Rogerson, C. Windpassinger, R. Strohal, M. Schmuth, P. Kroisel, A.R. Janecke, P. Gissen Tags: Genetics and Cell Based Therapy Source Type: research