Limb disorders

Gene: WDPCP

Comment on list classification: Promoting this gene to green. It has limited evidence in association with Bardet-Biedl syndrome 15, but there are 3 cases reported in association with Oral facial digital syndrome and plausible disease causing variants.

Created: 29 Nov 2019, 12:52 p.m. | Last Modified: 29 Nov 2019, 12:52 p.m.

Panel Version: 1.139

PMID: 28289185 - Bruel et al 2017 - report 1 case (patient 10) with compound heterozygous variants (a missense variant and 2bp deletion leading to a frameshift) in WDPCP and an Oral-facial-digital syndrome phenotype which includes Post-axial polydactyly of the hands and syndactyly of the feet.

PMID: 27158779 - Toriyama et al 2016 - report 1 case of a 5-year-old male presenting with facial dysmorphism, tongue hamartoma, high arched palate, tooth abnormalities, and postaxial polydactyly. He was found to be compound heterozygous for two mutations in WDPCP, a frameshift and a missense variant predicted to alter splicing. Each parent had one of the variants. Functional studies in Xenopus MCCs and found that the frame-shift allele resulted in total loss of protein, while the point mutation led to a consistent but more modest defect in protein stability They also observed Y-shaped metacarpals and defects in tongue and palate morphology in Wdpcp mouse mutants

PMID: 25427950 - Saari et al 2015 - report 1 case of a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas. By whole exome sequencing they found she is a compound heterozygote for a frame shift mutation and a likely pathogenic sequence variant in WDPCP. The parents and two siblings were heterozygous carriers.

PMID: Kim et al 2010 - report 1 cases of a proband with a clinical diagnosis of BBS and a homozygous Fritz mutation that segregated with the disorder. Both parents and an unaffected sib were heterozygous carriers. No details

3 cases with oralfacial digitial syndrome type phenotypes and one with a clinical diagnosis of BBS.

Created: 27 Nov 2019, 3:08 p.m. | Last Modified: 29 Nov 2019, 11:25 a.m.

Panel Version: 1.137

Comment on list classification: The Bardet-Biedl syndrome genes are being added back to this panel to avoid missing a potential diagnosis in the Genomic Medicine Service. This gene is amber on the GMS Bardet-Biedl syndrome panel https://panelapp.genomicsengland.co.uk/panels/543/ v1.0

Created: 25 Nov 2019, 10:08 p.m. | Last Modified: 25 Nov 2019, 10:10 p.m.

Panel Version: 1.104

Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.

Created: 2 Dec 2018, 11:15 p.m.

Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least 2 variants identified in a single case.

Created: 10 Sep 2018, 12:33 p.m.