Novel mutation in KRT14 gene caused EBS in father, son

Researchers share case report describing large deletion in the KRT14 gene

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A never-before-reported mutation in the KRT14 gene caused epidermolysis bullosa simplex (EBS) in a family in China.

The new mutation was described in the case report, “Large intragenic deletion of KRT14 causes autosomal-dominant epidermolysis bullosa simplex with generalized hyperpigmentation,” published in the Journal of Dermatological Science.

EBS is the most common type of epidermolysis bullosa. The vast majority of EBS cases are caused by mutations in the genes KRT5 or KRT14.

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Scientists in China reported the cases of two people with EBS: a 30-year-old Han Chinese man, and his 3-month-old son.

The father had developed blisters on his hands and feet as a a baby. When he was about 7 years old the blisters on his extremities diminished, but he started to develop blisters on his trunk. He also had generalized patchy hyperpigmentation (spots of darkened skin).

The 3-month-old was found to have blisters on his heels and ear, comparable to what his father had experienced at the same age. Apart from mild to moderate pruritus (itching), no other notable health issues were observed in either patient, and no one else in the family reported similar symptoms.

Skin biopsy taken from the father showed changes in skin layers and signs of inflammation consistent with epidermolysis bullosa, which prompted EB-targeted genetic testing to confirm the diagnosis.

Results revealed a novel mutation in the KRT14 gene. The specific mutation was a large deletion — meaning that a section of the gene, specifically from exon 3 to exon 8, was missing. An exon is a section of a gene that contains instructions for making protein.

When a gene like KRT14 is read to make a protein, the genetic code is copied into a temporary molecule called messenger RNA (mRNA), which is used as a template for making the protein. Analyses suggested that the deletion would lead to unstable KRT14 mRNA, causing the mRNA to be degraded through a process called nonsense-mediated decay (NMD). The early destruction of mRNA prevents normal production of the K14 protein encoded by the KRT14 gene.

“These results suggested that the large deletion of KRT14 resulted in NMD of the aberrant [mRNA] and decrease of K14 expression,” the researchers concluded.

Everyone inherits two copies of the KRT14 gene, one from each biological parent. In these cases, both the man and his child had one mutated copy of KRT14, while the other copy of the gene showed no mutation, referred to as heterozygous.

Autosomal dominant inheritance

This suggests that EBS caused by this deletion in KRT14 is inherited in an autosomal dominant manner — meaning just one copy of the mutated gene is enough to cause disease.

“We first report on an autosomal-dominant EBS with relatively mild [symptoms] and generalized hyperpigmentation with heterozygous large intragenic deletion in KRT14, expanding the spectrum of clinical manifestations associated with KRT14,” the researchers concluded.