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PORCN gene mutations and the protean nature of focal dermal hypoplasia.
Br J Dermatol. 2009 May; 160(5):1103-9.BJ

Abstract

Focal dermal hypoplasia (FDH) is an X-linked dominant disorder featuring developmental abnormalities of ectodermal and mesodermal tissues. Pathogenic mutations in the PORCN gene (locus Xp11.23) were identified in 2007 and thus far 27 different mutations have been reported. PORCN encodes a putative O-acyltransferase which facilitates secretion of Wnt proteins required for ectomesodermal tissue development. We investigated PORCN gene pathology and pattern of X-chromosome inactivation analysis in two unrelated Caucasian female patients who presented with multiple developmental abnormalities consistent with FDH. We also reviewed the clinical and molecular data for all reported PORCN mutations and assessed genotype-phenotype correlation for sporadic and familial cases of FDH. DNA sequencing revealed two new PORCN gene mutations: p.W282X and c.74delG (p.G25fsX51). X-chromosome inactivation analysis revealed a random pattern in one case but was uninformative in the other. Collectively, point/small mutations account for 24 out of the 29 PORCN mutations and are typically seen in sporadic cases; larger deletions are more common in familial cases. Identification of two new PORCN gene mutations confirms the importance of PORCN-associated Wnt signalling in embryogenesis. Both new cases showed Blaschko-linear dermal hypoplasia and extensive ectomesodermal abnormalities, including severe limb developmental anomalies and a giant cell tumour of bone in one patient. Clinical variability can be attributed to the degree of lyonization and postzygotic genomic mosaicism, which are important mechanisms in determining the clinical presentation.

Authors+Show Affiliations

Genetic Skin Disease Group, St John's Institute of Dermatology, King's College London, Guy's Campus, London, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19292719

Citation

Clements, S E., et al. "PORCN Gene Mutations and the Protean Nature of Focal Dermal Hypoplasia." The British Journal of Dermatology, vol. 160, no. 5, 2009, pp. 1103-9.
Clements SE, Mellerio JE, Holden ST, et al. PORCN gene mutations and the protean nature of focal dermal hypoplasia. Br J Dermatol. 2009;160(5):1103-9.
Clements, S. E., Mellerio, J. E., Holden, S. T., McCauley, J., & McGrath, J. A. (2009). PORCN gene mutations and the protean nature of focal dermal hypoplasia. The British Journal of Dermatology, 160(5), 1103-9. https://doi.org/10.1111/j.1365-2133.2009.09048.x
Clements SE, et al. PORCN Gene Mutations and the Protean Nature of Focal Dermal Hypoplasia. Br J Dermatol. 2009;160(5):1103-9. PubMed PMID: 19292719.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PORCN gene mutations and the protean nature of focal dermal hypoplasia. AU - Clements,S E, AU - Mellerio,J E, AU - Holden,S T, AU - McCauley,J, AU - McGrath,J A, Y1 - 2009/03/09/ PY - 2009/3/19/entrez PY - 2009/3/19/pubmed PY - 2009/7/16/medline SP - 1103 EP - 9 JF - The British journal of dermatology JO - Br J Dermatol VL - 160 IS - 5 N2 - Focal dermal hypoplasia (FDH) is an X-linked dominant disorder featuring developmental abnormalities of ectodermal and mesodermal tissues. Pathogenic mutations in the PORCN gene (locus Xp11.23) were identified in 2007 and thus far 27 different mutations have been reported. PORCN encodes a putative O-acyltransferase which facilitates secretion of Wnt proteins required for ectomesodermal tissue development. We investigated PORCN gene pathology and pattern of X-chromosome inactivation analysis in two unrelated Caucasian female patients who presented with multiple developmental abnormalities consistent with FDH. We also reviewed the clinical and molecular data for all reported PORCN mutations and assessed genotype-phenotype correlation for sporadic and familial cases of FDH. DNA sequencing revealed two new PORCN gene mutations: p.W282X and c.74delG (p.G25fsX51). X-chromosome inactivation analysis revealed a random pattern in one case but was uninformative in the other. Collectively, point/small mutations account for 24 out of the 29 PORCN mutations and are typically seen in sporadic cases; larger deletions are more common in familial cases. Identification of two new PORCN gene mutations confirms the importance of PORCN-associated Wnt signalling in embryogenesis. Both new cases showed Blaschko-linear dermal hypoplasia and extensive ectomesodermal abnormalities, including severe limb developmental anomalies and a giant cell tumour of bone in one patient. Clinical variability can be attributed to the degree of lyonization and postzygotic genomic mosaicism, which are important mechanisms in determining the clinical presentation. SN - 1365-2133 UR - https://www.unboundmedicine.com/medline/citation/19292719/PORCN_gene_mutations_and_the_protean_nature_of_focal_dermal_hypoplasia_ L2 - https://doi.org/10.1111/j.1365-2133.2009.09048.x DB - PRIME DP - Unbound Medicine ER -