Novel and recurrent PORCN gene mutations in almost unilateral and typical focal dermal hypoplasia patients

Gen Nakanishi, Kousei Hasegawa, Takashi Oono, Shigeki Koshida, Noriki Fujimoto, Keiji Iwatsuki, Hiroyuki Tanaka, Toshihiro Tanaka

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Goltz syndrome or Focal dermal hypoplasia (FDH) is an X-linked dominant disorder characterized by malformations affecting the skin, eyes, central nervous system, and skeletonC:\GetARef\Refs\focal dermal hypoplasia (2007-).re. Mutations in the PORCN gene were identified as the molecular basis of FDH. We report two cases, one caused by a current mutation c.129G>A, which leads to a nonsense mutation W43X, and the other one caused by a novel mutation, c.386delT. The female patient with the recurrent mutation presented with typical cutaneous symptoms and skeletal abnormality, but the female patient with the novel mutation manifested only cutaneous symptoms, with hypo-pigmentation along Blaschko's lines, mainly on her right hemibody. In the latter case, DNA was isolated from peripheral blood cells, lesional skin, and nonlesional skin. The percentage of cells carrying the mutation estimated by subcloning and sequencing of the PCR products was 3.1% in peripheral blood cells, 21% in lesional skin, and 16% in non-lesional skin. X-chromosome inactivation assay showed a slightly skewed pattern in lesional skin, but a random pattern in non-lesional skin and blood. RTPCR analysis from skin samples showed that PORCN mRNA of the mutated allele had a 13bp nucleotide insertion created by an alternative splicing site. This resulted in abnormal PORCN protein with in-frame insertion of eight amino acids, TTHRGTDD, instead of the original four amino acids, AQMI (126-129). We report a typical FDH patient with a recurrent PORCN mutation, which was previously identified in a male Japanese FDH patient, and a second femal, an almost unilateral FDH patient with a postzygotic PORCN mutation.

Original languageEnglish
Pages (from-to)64-67
Number of pages4
JournalEuropean Journal of Dermatology
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 2013

Fingerprint

Focal Dermal Hypoplasia
Skin
Mutation
Genes
Blood Cells
Amino Acids
X Chromosome Inactivation
Nonsense Codon
Pigmentation
Alternative Splicing

Keywords

  • Focal dermal hypoplasia
  • Mosaic
  • Mutation
  • PORCN

ASJC Scopus subject areas

  • Dermatology

Cite this

Novel and recurrent PORCN gene mutations in almost unilateral and typical focal dermal hypoplasia patients. / Nakanishi, Gen; Hasegawa, Kousei; Oono, Takashi; Koshida, Shigeki; Fujimoto, Noriki; Iwatsuki, Keiji; Tanaka, Hiroyuki; Tanaka, Toshihiro.

In: European Journal of Dermatology, Vol. 23, No. 1, 01.2013, p. 64-67.

Research output: Contribution to journalArticle

Nakanishi, Gen ; Hasegawa, Kousei ; Oono, Takashi ; Koshida, Shigeki ; Fujimoto, Noriki ; Iwatsuki, Keiji ; Tanaka, Hiroyuki ; Tanaka, Toshihiro. / Novel and recurrent PORCN gene mutations in almost unilateral and typical focal dermal hypoplasia patients. In: European Journal of Dermatology. 2013 ; Vol. 23, No. 1. pp. 64-67.
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