PhenoModifier-Variant Detail

Variant "KRT16:c.395T>C(p.Leu132Pro)"

Search result: 1 record

Variant information

Gene:

KRT16

Variant:

KRT16:c.395T>C(p.Leu132Pro)

Genomic location:

chr17:39768546(hg19)

HGVS:

SO Term	RefSeq
protein_coding	NM_005557.3:c.395T>C(p.Leu132Pro)

dbSNP ID:

rs60944949

GWAS trait:

no data

Modifier statisitcs

Record:

1

Disorder:

1

Reference:

1

Effect type:

Expressivity(1)

Modifier effect:

Altered severity(1)

Detail：

Target disease:

Pachyonychia Congenita (DOID_0050449)

Effect type:

Expressivity

Modifier effect:

Altered severity

Evidence:

Pedigree analysis

Effect:

Coinheritance of mutations in KRT16 and FLG may aggravate the PC phenotype and that FLG could serve as a genetic modifier in PC.

Reference:

PMID19785597

Title:

Increased pachyonychia congenita severity in patients with concurrent keratin and filaggrin mutations.

Species studied:

Human

Abstract:

Pachyonychia congenita (PC), a rare autosomal-dominant keratin disorder caused by mutations in keratin genes KRT6A/B, KRT16 or KRT17, is characterized by painful plantar keratoderma and hypertrophic nail dystrophy. Loss-of-function mutations in the filaggrin (FLG) gene underlie the most prevalent skin disorder of cornification, ichthyosis vulgaris (IV), which presents with generalized scaling and is also associated with atopic dermatitis. Recently, FLG mutations have been reported to increase phenotype severity of X-linked ichthyosis and alopecia areata. We report a parent-child trio in which the mother and the son have PC and the father has IV. Both the mother and the son are carriers for the KRT16 mutation p.Leu132Pro. The son, who is much more severely affected than his mother, in addition carries the heterozygous FLG mutation p.R2447X, which was inherited from the father. This observation suggests that coinheritance of mutations in KRT16 and FLG may aggravate the PC phenotype and that FLG could serve as a genetic modifier in PC.