+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Compound heterozygosity for a frame shift mutation and a likely pathogenic sequence variant in the planar cell polarity—ciliogenesis gene WDPCP in a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas



Compound heterozygosity for a frame shift mutation and a likely pathogenic sequence variant in the planar cell polarity—ciliogenesis gene WDPCP in a girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas



American Journal of Medical Genetics. Part a 167a(2): 421-427



We report on a young girl with polysyndactyly, coarctation of the aorta, and tongue hamartomas. These features are similar to those reported in individuals with variant forms of orofaciodigital syndrome known as congenital heart defects, hamartomas of the tongue and polysyndactly (CHDHTP: OMIM 217085) [Örstavik et al., 1992] and orocardiodigital syndrome [Digilio et al., 1996]. Whole exome sequencing revealed that she is a compound heterozygote for a frame shift mutation and a likely pathogenic sequence variant in WDPCP, a gene that regulates planar cell polarity and ciliogenesis. Results of genotyping in her parents and unaffected siblings were consistent with autosomal recessive inheritance of the mutation and the WDPCP variant. These results suggest that disruption of planar cell polarity and ciliogenesis may result in this unusual form of orofaciodigital syndrome.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 057480972

Download citation: RISBibTeXText

PMID: 25427950

DOI: 10.1002/ajmg.a.36852


Related references

Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton. Plos Biology 11(11): E1001720, 2013

The planar cell polarity effector protein Wdpcp (Fritz) controls epithelial cell cortex dynamics via septins and actomyosin. Biochemical and Biophysical Research Communications 456(2): 562-566, 2015

Compound heterozygosity for an out-of-frame deletion and a splice site mutation in the LAMB3 gene causes nonlethal junctional epidermolysis bullosa. Biochemical and Biophysical Research Communications 243(3): 758-764, 1998

Intermediate hyperhomocysteinaemia and compound heterozygosity for the common variant c.677C>T and a MTHFR gene mutation. Journal of Inherited Metabolic Disease 30(3): 401, 2007

An 18 bps in-frame deletion mutation in RUNX2 gene is a population polymorphism rather than a pathogenic variant. European Journal of Medical Genetics 62(2): 124-128, 2019

Planar cell polarity, ciliogenesis and neural tube defects. Human Molecular Genetics 15 Spec no 2: R227-R234, 2006

Congenital heart defects hamartomas of the tongue and polysyndactyly in a sister and brother. Clinical Genetics 42(1): 19-21, 1992

Planar cell polarity acts through septins to control collective cell movement and ciliogenesis. Science 329(5997): 1337-1340, 2010

From Planar Cell Polarity to Ciliogenesis and Back: The Curious Tale of the PPE and CPLANE proteins. Trends in Cell Biology 27(5): 379-390, 2017

The Trp73 Mutant Mice: A Ciliopathy Model That Uncouples Ciliogenesis From Planar Cell Polarity. Frontiers in Genetics 10: 154, 2019

Mutation of the Planar Cell Polarity Gene VANGL1 in Adolescent Idiopathic Scoliosis. Spine 42(12): E702-E707, 2017

Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polarity and Hedgehog signaling. Nature Genetics 38(3): 303-311, 2006

Frame-shift mutation and reduced transcript of p53 gene in a renal cell carcinoma cell line, RCC23. Human Molecular Genetics 4(4): 771-773, 1995

A patient with the rare alpha-1-antitrypsin variant (Z)bristol in compound heterozygosity with the Z mutation. Annals of Clinical Biochemistry 50(Pt 6): 618-621, 2013

A Severe Case of Congenital Thrombotic Thrombocytopenia Purpura Resulting From Compound Heterozygosity Involving a Novel ADAMTS13 Pathogenic Variant. Journal of Pediatric Hematology/Oncology 40(1): 60-62, 2018