Epidermolysis Bullosa Simplex with KLHL24 MutationsQ82.8

Last updated on: 07.01.2022

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DefinitionThis section has been translated automatically.

Extensive (non-pyodermic) erosions are already present at birth, preferably on the extremities. These heal with tender scarring and mild hyperpigmentation. Traumatic blistering occurs in adolescence.

KLHL24 mutations can cause extracutaneous disease in humans in addition to the obvious cutaneous symptoms, with dilated cardiomyopathy being a strong association (Bolling MC et al. 2019). In addition, neurological diseases are also associated with mutations in KLHL24.

To what extent the cardiogenic component is associated only with specific variants popular currently still subject of research. A de novo pathogenic variant (c.2T>C (p.M1T) in KLHL24 (NM_017,644) appears to be associated with dermatologic symptomatology only (Xu X et al. 2021).

EtiopathogenesisThis section has been translated automatically.

In epidermolysis bullosa simplex with mutation in KLHL24, whole-exome sequencing and targeted sequencing detected monoallelic mutations, c.1A>G and c.2T>C, in the translation initiation codon of the gene encoding Kelch-like protein 24 (KLHL24). These result in the encoding of a truncated polypeptide, abnormalities of intermediate filaments in keratinocytes and fibroblasts.KLHL24 mutations are associated with irregular and fragmented keratin 14. The c.1A>G mutation occurred de novo and was repeated in families from different countries (He Y et al. 2016).

Progression/forecastThis section has been translated automatically.

Improvement of the dermatological symptomatology in the course of life

Note(s)This section has been translated automatically.

KLHL24 (KLHL24 is the acronym for Kelch Like Family Member 24) is a protein coding gene located on chromosome 3q27.1. KLHL24 is a member of the Kelch-like family of proteins that function as substrate-specific adaptors for cullin E3 ubiquitin ligases. The encoded protein is necessary for maintaining the balance between stability and degradation of intermediate filaments, a process essential for the integrity of the skin as well as the heart, among others. KLHL24 mutations are a cause of skin fragility but also of hereditary dilated cardiomyopathy.

LiteratureThis section has been translated automatically.

  1. Alkhalifah A et al (2018) Burnlike scars: A sign suggestive of KLHL24-related epidermolysis bullosa simplex. Pediatr Dermatol 35:e193-e195.
  2. Bolling MC et al (2019) KLHL24: Beyond Skin Fragility. J Invest Dermatol139: 22-24.
  3. El Hachem M et al. (2019) Phenotypic Features of Epidermolysis Bullosa Simplex due to KLHL24 Mutations in 3 Italian Cases. Acta Derm Venereol 99: 238-239.
  4. Has C (2017) The "chalice" surprise: KLHL24, a New Player in the Pathogenesis of Skin Fragility. J Invest Dermatol 137: 1211-1212.
  5. He Y et al (2016) Monoallelic mutations in the translation initiation codon of KLHL24 cause skin fragility. Am J Hum Genet 99: 1395-1404.
  6. Lee JYW et al (2017) Mutations in KLHL24 Add to the Molecular Heterogeneity of Epidermolysis Bullosa Simplex. J Invest Dermatol 137:1378-1380.
  7. Schwieger-Briel A et al (2019) Epidermolysis Bullosa Simplex with KLHL24 Mutations Is Associated with Dilated Cardiomyopathy. J Invest Dermatol 139:244-249.
  8. Xu X et al (2021) Case Report: De novo KLHL24 Gene Pathogenic Variants in Chinese Twin Boys With Epidermolysis Bullosa Simplex. Front Genet 12:729628.

Last updated on: 07.01.2022