KRT10 – Autosomal recessive epidermolytic ichthyosis

Autosomal recessive epidermolytic ichthyosis is a rare skin disorder characterized by erythroderma and superficial blistering at birth, followed by hyperkeratosis and skin fragility. Biallelic loss-of-function variants in KRT10 impair keratin 10 expression, disrupting the keratin intermediate filament network in suprabasal keratinocytes.

A single case of self-improving epidermolytic ichthyosis was described in an infant with compound heterozygous KRT10 variants: one premature termination codon and one synonymous splice-site change causing leaky exon 3 splicing and residual keratin 10 expression, explaining the mild, spontaneously improving phenotype (n=1 proband) (PMID:31278741).

In a consanguineous Venezuelan family, four affected individuals harbored a homozygous non-sense variant c.846C>A (p.Tyr282Ter) in the 1B rod domain of KRT10, resulting in complete absence of keratin 10, compensatory upregulation of K14 and K17, and classic epidermolytic hyperkeratosis (PMID:23957016).

Human molecular genetic analysis of a recessive kindred revealed a homozygous nonsense mutation c.1300C>T (p.Gln434Ter) leading to transcript degradation and complete loss of keratin 10 protein. Affected individuals exhibited severe epidermolytic hyperkeratosis with induction of wound-healing keratins K6/K16/K17, confirming that KRT10 haploinsufficiency causes the phenotype (PMID:16505000).

Functional studies underscore a loss-of-function mechanism: decreased keratin 10 levels due to mRNA decay or absent protein correlates with impaired filament assembly and skin fragility. The mild phenotype in the compound heterozygote highlights the impact of residual expression from leaky splicing.

No conflicting evidence has been reported for recessive KRT10 variants. The combined data across five unrelated human probands, segregation in a consanguineous pedigree, and concordant functional models support a robust gene–disease link.

Key take-home: Biallelic KRT10 loss-of-function variants cause autosomal recessive epidermolytic ichthyosis by abolishing keratin 10, with variable severity modulated by residual protein expression.

References

• The British journal of dermatology • 2020 • Skin fragility caused by biallelic KRT10 mutations: an intriguing form of self-improving epidermolytic ichthyosis. PMID:31278741
• Molecular genetics & genomic medicine • 2013 • A Novel non-sense Mutation in Keratin 10 Causes a Familial Case of Recessive Epidermolytic Ichthyosis. PMID:23957016
• Human molecular genetics • 2006 • A human keratin 10 knockout causes recessive epidermolytic hyperkeratosis. PMID:16505000

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