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. 2025 Feb 4;18(1):26.
doi: 10.1186/s12920-024-02077-1.

A pathogenic COL7A1 variant highlights semi-dominant inheritance in dystrophic epidermolysis bullosa

Saira Sattar  1   2 , Thashi Bharadwaj  2 , Umm-E- Kalsoom  3 , Anushree Acharya  2 , Saadullah Khan  4 , Suzanne M Leal  2   5 , Isabelle Schrauwen  6   7
Affiliations

A pathogenic COL7A1 variant highlights semi-dominant inheritance in dystrophic epidermolysis bullosa

Saira Sattar et al. BMC Med Genomics. .

Abstract

Dystrophic epidermolysis bullosa is a rare subtype of inherited epidermolysis bullosa, caused by variants in the collagen type VII alpha 1 chain (COL7A1) gene (MIM120120). Both autosomal dominant and recessive inheritance has been reported with variable phenotype. We investigated a Pakistani family with dystrophic epidermolysis bullosa via exome sequencing and identified a pathogenic nonsense variant in COL7A1 NM_000094 c.1573 C > T:p.(Arg525*). The inheritance pattern observed was consistent with a semi-dominant model, where heterozygous parents exhibited a mild phenotype, and homozygous children were more severely affected. For dystrophic epidermolysis bullosa, loss-of-function variants are typically associated with the autosomal recessive form, while missense variants are linked to the autosomal dominant form. A review of the literature suggests a semi-dominance pattern for some missense variants, particularly glycine substitutions, but this concept had not been formally recognized. This study highlights the importance of considering semi-dominant inheritance models for dystrophic epidermolysis bullosa and other Mendelian diseases with an autosomal recessive mode of inheritance, as it can significantly impact diagnosis and genetic counseling.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The research study was approved by Institutional review board of Hazara University, Mansehra, Pakistan (IF.No.HU/ORIC/2023/1230) and Columbia University New York, USA (AAAS3431). Informed written consent was taken from participating members of family. Blood sampling from unaffected and affected individuals were carried out according to guidelines provided by Declaration of Helsinki. Consent for publication: We hereby provide our explicit consent for the publication of our research materials, including clinical details and images, on behalf of patients who have given written consent for publication, subject to approval by the Board of BMC Medical Genomics. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Pedigree of family ED-5 (COL7A1). The consanguineous pedigree with segregation of the COL7A1 [c.1573 C > T:p.(Arg525*)] variant. Squares indicate the males, circles female and filled black filed symbols represent individuals with severe dystrophic epidermolysis bullosa and grey filled symbols individuals with a milder form of dystrophic epidermolysis bullosa. Double lines indicate consanguinity and individuals with a line through the symbol indicates they are deceased
Fig. 2
Fig. 2
Clinical presentation. Images (A-D) show nail dystrophy, Beau’s lines, club nails and dry skin of the affected father (II:6), images (E) and (F) display the black tartar teeth of the affected mother (II:5) and images (G-L) show the phenotypes of affected child (II:2), image (G-I) shows blistering all over the left and right foot, erosions and erythematous skin, dryness, image (J) dryness and blisters on hands image (K) shows nail dystrophy and club nails of affected child, image (L) shows skin dryness, milia, and a yellowish crusted lesion present on the ear
See this image and copyright information in PMC

References

    1. Fine JD. Epidermolysis bullosa: clinical, epidemiologic, and laboratory advances, and the findings of the National Epidermolysis Bullosa Registry. Baltimore: Johns Hopkins University; 1999.
    1. Fine JD, Eady RAJ, Bauer EA, Bauer JW, Bruckner-Tuderman L, Heagerty A, et al. The classification of inherited epidermolysis bullosa (EB): report of the Third International Consensus Meeting on diagnosis and classification of EB. J Am Acad Dermatol. 2008;58(6):931–50. - PubMed
    1. Fine JD. Inherited epidermolysis bullosa. Orphanet J Rare Dis. 2010;5(1):12. - PMC - PubMed
    1. Fine JD, Bruckner-Tuderman L, Eady RAJ, Bauer EA, Bauer JW, Has C, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014;70(6):1103–26. - PubMed
    1. Has C, Bauer JW, Bodemer C, Bolling MC, Bruckner-Tuderman L, Diem A, et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020;183(4):614–27. - PubMed

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