ArticleHuman molecular genetics2017
Revertant mosaicism repairs skin lesions in a patient with keratitis-ichthyosis-deafness syndrome by second-site mutations in connexin 26.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 29 citations in OpenAlex.
- Methods for Chromosome-Scale Haplotype Reconstruction.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Long-read sequencing for brain tumors.Frontiers in oncology · 2024Review
- Revertant Mosaicism in Genodermatoses: Natural Gene Therapy Right before Your Eyes.Biomedicines · 2022Review
- Computational methods for chromosome-scale haplotype reconstruction.Genome biology · 2021Review
- Cutaneous Melanoma Classification: The Importance of High-Throughput Genomic Technologies.Frontiers in oncology · 2021Review
- Mosaicism in Human Health and Disease.Annual review of genetics · 2020Review
- A six-attribute classification of genetic mosaicism.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Review
- Sjögren-Larsson syndrome: The mild end of the phenotypic spectrum.JIMD reports · 2020Article
- The third generation sequencing: the advanced approach to genetic diseases.Translational pediatrics · 2020Review
- Ichthyosis: A Road Model for Skin Research.Acta dermato-venereologica · 2020Review
- Revertant mosaic fibroblasts in recessive dystrophic epidermolysis bullosa.The British journal of dermatology · 2019Article
- Somatic recombination underlies frequent revertant mosaicism in loricrin keratoderma.Life science alliance · 2019Article
- Long-Read Sequencing Emerging in Medical Genetics.Frontiers in genetics · 2019Review
- Single molecule real-time (SMRT) sequencing comes of age: applications and utilities for medical diagnostics.Nucleic acids research · 2018Review
- A novel approach using long-read sequencing and ddPCR to investigate gonadal mosaicism and estimate recurrence risk in two families with developmental disorders.Prenatal diagnosis · 2017Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Revertant mosaicism (RM) is a naturally occurring phenomenon where the pathogenic effect of a germline mutation is corrected by a second somatic event. Development of healthy-looking skin due to RM has been observed in patients with various inherited skin disorders, but not in connexin-related disease. We aimed to clarify the underlying molecular mechanisms of suspected RM in the skin of a patient with keratitis-ichthyosis-deafness (KID) syndrome. The patient was diagnosed with KID syndrome due to characteristic skin lesions, hearing deficiency and keratitis. Investigation of GJB2 encoding connexin (Cx) 26 revealed heterozygosity for the recurrent de novo germline mutation, c.148G > A, p.Asp50Asn. At age 20, the patient developed spots of healthy-looking skin that grew in size and number within widespread erythrokeratodermic lesions. Ultra-deep sequencing of two healthy-looking skin biopsies identified five somatic nonsynonymous mutations, independently present in cis with the p.Asp50Asn mutation. Functional studies of Cx26 in HeLa cells revealed co-expression of Cx26-Asp50Asn and wild-type Cx26 in gap junction channel plaques. However, Cx26-Asp50Asn with the second-site mutations identified in the patient displayed no formation of gap junction channel plaques. We argue that the second-site mutations independently inhibit Cx26-Asp50Asn expression in gap junction channels, reverting the dominant negative effect of the p.Asp50Asn mutation. To our knowledge, this is the first time RM has been reported to result in the development of healthy-looking skin in a patient with KID syndrome.
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