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NM_000526.5(KRT14):c.1151T>C (p.Leu384Pro) AND Epidermolysis bullosa simplex, Koebner type

Significance: Pathogenic
ClinVar: RCV000015715

Variant: NM_000526.5(KRT14):c.1151T>C (p.Leu384Pro)

Type: Variant
Allele: NM_000526.5(KRT14):c.1151T>C (p.Leu384Pro) 29650
Gene:
Type: single nucleotide variant
Location: Chr17: 41583358 - assembly GRCh38
Chr17: 39739610 - assembly GRCh37
References: dbSNP: 59629244
OMIM: 148066.0001
UniProtKB: P02533#VAR_003843

Condition

Disease: Epidermolysis bullosa simplex, Koebner type

Citation

    In a family with generalized epidermolysis bullosa simplex of the Koebner type (131900), Bonifas et al. (1991) demonstrated linkage of the disorder to the gene encoding keratin 14. Further studies demonstrated a T-to-C substitution at bp 3542 in exon 6 resulting in a change of amino acid 384 from leucine to proline. The mutation created a new MspI site. It is notable that finding the particular mutation was a 'stroke of luck.' No polymorphism of the KRT14 gene was known and linkage of EBS to DNA markers in the family in question were inconclusive. Bonifas et al. (1991), however, hybridized a 3-prime untranslated KRT14 probe to DNA from members of the family digested with 9 restriction endonucleases. This revealed the unique MspI restriction site change which was tightly linked to EBS in this family with a lod score of 3.0. It was found in all affected members and in no unaffected members. Vassar et al. (1991) produced basal keratinocyte fragility causing neonatal death in mice carrying a transgene encoding a shortened KRT14. The phenotype of the human disease caused by the leu384-to-pro mutation is much less severe than that caused by deletion of 135 amino acids from the KRT14 carboxyl terminus in the transgenic mice.
PMID:1703046, PMID:1720261