John Libbey Eurotext

European Journal of Dermatology


Deep-intronic and frameshift DSG1 variants associated with atypical severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome in a Chinese family Article à paraître


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1 Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
2 Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, China
3 Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, China
4 NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
* Reprints
a These authors contributed equally

Background: Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome comprise a rare genodermatosis associated with biallelic (homozygous or compound heterozygous) mutations in the DSG1 (desmoglein-1) gene, or heterozygous mutations in the DSP (desmoplakin) gene. To date, while many patients with SAM syndrome have been described, the number of cases with SAM syndrome with deep-intronic variants, together its genetic aetiology, remain limited. Objective: We report the case of a five-year-old Chinese boy with atypical SAM syndrome. Materials & Methods: Relevant blood specimens from the family were collected. DNA isolation, RNA isolation and cDNA synthesis, and next-generation sequencing using a multi-gene panel were applied to verify the pathogenic gene. To test the functional consequences and pathogenic mechanism of the deep-intronic mutation in vitro, a mini gene strategy was constructed. Results: A heterozygous DSG1 deletion (c.2437_2450delACCTATCCCTCGGG: p.Tyr814Trpfs*6) and a deep-intronic (c.1688-30A > T) variant were identified. The identified intronic variant was shown to create an alternative splice site, leading to nonsense-mediated mRNA decay of the aberrant transcript. Conclusion: This is the first study to demonstrate a causal role for a deep-intronic DSG1 mutation in a patient with SAM syndrome. Our findings underline the need to analyse the intronic regions of DSG1 in patients with SAM syndrome. Improved diagnosis and a better understanding of prognosis will lead to clearer a picture of the concept of atypical SAM syndrome.