ClinGen Dosage Sensitivity Curation Page

PORCN

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
17546030 Wang et al. (2007) report on 15 females with confirmed or suspected focal dermal hypoplasia (FDH). Sequencing of the PORCN gene in these individuals revealed mutations in 10 of the 15 individuals, with nonsense mutations and frameshift mutations resulting in premature stop codon present in the majority of individuals with PORCN mutations.
17546031 Grzeschik et al. (2007) describe loss of function mutations of the PORCN gene in 8 unrelated individuals with FDH.
20854095 Fernandes et al. (2010) describe their experience with clinical genetic testing of the PORCN gene in individuals with FDH. Mutations were found in 18 out of 53 patients tested (34%).

Haploinsufficiency phenotype comments:

Haploinsufficiency of PORCN results in focal dermal hypoplasia (aka Goltz syndrome), a multisystem disorder involving skin, skeletal system, eyes, and face. Common features include atrophy and linear pigmentation of the skin, deposition of subcutaneous fat into the dermis, digital anomalies, oral anomalies, and eye anomalies including anophthalmia/microphthalmia, and colobomas. Intellectual disability is reported in approximately 15% of individuals with FDH. 90% of FDH patients are females, with the male cases typically resulting from somatic mosaicism.

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.