Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria

Cao, Lu; Zhang, Ruixue; Chen, Shirui; Zhang, Hui; Chen, Weiwei; Xu, Qi; Ge, Huiyao; Mao, Yan; Zhen, Qi; Yu, Yafen; Hu, Xia; Sun, Liangdan

doi:10.1186/s12920-021-01014-w

Cited by 10 publications

(14 citation statements)

References 26 publications

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“…Our study provides a novel pathogenic variant of PER3 of DUH and contributes to the identi cation of causal genes for DUH. Different from the DUH clinical phenotypes previously reported, with lesions of irregular size and shape always appearing in infancy or early childhood [4,11,[41][42][43], in our study, clinical symptoms on the bodies of six affected individuals except those on the proband were mild , hyperpigmented phenotypes especially the hypopigmented ones of which were often ignored according to their self-memory and descriptions. Different clinical manifestations were demonstrated in the I-2, II-3, II-10, II-11, III-9 and III-12 affected individuals with mild clinical phenotypes This may indicate that a novel DUH subtype with autosomal dominant inheritance and mild pigmentated phenotypes were caused by the PER3 P173S SNP.…”

Section: Discussioncontrasting

confidence: 99%

The PER3rs772027021 SNP induces pigmentation phenotypes of dyschromatosis universalis hereditaria

Chen

Yang

et al. 2023

J Mol Med

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Dyschromatosis universalis hereditaria (DUH) is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body. Although Sterile Alpha motif-and SH3 domain-containing protein 1 ( SASH1 ) and ATP-binding cassette subfamily B, member 6 ( ABCB6 ) have been identi ed as causative genes for this disorder, some cases involve unknown pathogenic genes. In this study, whole-exome sequencing, data analysis and Sanger sequencing were utilized for a fourgeneration extended Chinese family with DUH. A single-nucleotide polymorphism (SNP) (c. 517C>T (p. P173S ), rs772027021) variant in exon 5 of Period Circadian Regulator 3 ( PER3 ) (NM_001289861) was detected in each affected individual of the DUH family; the c. 517C>T SNP of PER3 ( PER3 rs772027021 SNP) and a novel mutation in exon 14 of SASH1 (c. 1574C>G (p.T525R)) were both found in the proband. The affected individuals carrying PER3 rs772027021 SNP in this family demonstrated mild pigmented phenotypes compared to those of the proband carrying PER3 rs772027021 SNP and SASH1 T525R mutation. Increased melanin synthesis was induced by PER3 rs772027021 SNP in the melanocytes of affected epithelial tissues. Mutated SASH1 or PER3 rs772027021 SNP alone or cooperation of mutation of SASH1 and PER3 rs772027021 SNP synergistically led to increased melanin synthesis and enhanced proliferation of melanoma cells in vitro. We also phenotypically characterized a commercially available zebra sh mutant line harboring the PER3 rs772027021 SNP to induce melanocyte proliferation in vivo . Our results are the rst to reveal that this PER3 SNP may be pathogenic for a novel DUH subtype with mild hyperpigmented and/or hypopigmented phenotypes and that mutation of SASH1 and PER3 cooperatively promotes hyperpigmentation phenotypes.

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Section: Discussioncontrasting

confidence: 99%

The PER3rs772027021 SNP induces pigmentation phenotypes of dyschromatosis universalis hereditaria

Chen

Yang

et al. 2023

J Mol Med

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“…In recent years, SASH1 variants have been implicated in different pigmentation disorders, prompting investigations into the role of SASH1 in dermatosis. [1,18] Studies have confirmed that SASH1 is a disease-causing locus for DUH and generalized lentiginosis, which typically exhibit an autosomal dominant trait with heterozygous mutations. [1] Research using epidermal tissues from DUH-affected individuals has shown that SASH1 upregulation promotes melanocyte migration and cell binding.…”

Section: Discussionmentioning

confidence: 99%

Uncovering a new SASH1 mutation associated with dyschromatosis universalis hereditaria using whole-exome-sequencing: A case report

Yang,

Jiang,

Mai

et al. 2023

Medicine

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Rationale: Dyschromatosis universalis hereditaria (DUH) is an uncommon form of pigmented genodermatosis that is typically inherited autosomally and dominantly. In the previous study, the pathogenic genes of DUH have been identified in ATP-binding cassette subfamily B, member 6 and SASH1. However, the mutational screening of the causative gene remains incomplete and still lacks sufficient proof in the etiology. Patient concerns: A 2-generation Chinese family clinically diagnosed with DUH were enrolled. They showed pigmented spots from their childhood and came to the hospital for medical advice and genetic analysis. We found a novel mutation c.1757T > C (p.I586T) of SASH1 in 3 affected family members by whole-exome sequencing. Diagnoses: Genetic outcomes and clinical examinations confirmed the diagnosis of DUH in 3 family members with lentiginous syndrome. Interventions and outcomes: Using whole-exome sequencing and sanger sequencing technologies, we identified a novel mutation c.1757T > C (p.I586T) of SASH1 that co-segregated in 3 afflicted family members but not in the normal individuals. Significantly, c.1757T > C (p.I586T) is a novel mutation which had not been previously reported. The same codon position in SASH1 (c.1758C > G, p.I586M) has been reported in a Japanese man, and he showed identical phenotype compared to our study participants. Lessons: Our study broadens the spectrum of DUH mutations and provides more genetic characteristics of DUH in understanding its etiology. Furthermore, we demonstrated the diagnostic accuracy of whole-exome sequencing for inherited skin diseases and provided new information for etiological study.

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“…8 Systemic damage, including deafness, visual impairment and neurological symptoms are presented in some DUH cases. 8 In 2003, two large families (a five-generation pedigree [Family A] and a three-generation pedigree [Family B]) from the Henan and Yunnan provinces of China segregating autosomal dominant cutaneous dyschromatosis were reported by our team. A mixture of hypopigmented and hyperpigmented macules of various sizes was shown on the trunks, arms, necks and faces of the affected individuals (Figure 1A,B).…”

Section: Clinical Phenotypic Characteristics Of Duh1mentioning

confidence: 99%

“…7 Therefore, DUH is divided into three types, DUH1 (OMIM 127500), DUH2 (OMIM 612715) and DUH3 (OMIM 615402) according to the different linkage regions located in the 6q24.2-q25.2, 12q21q23 and 2q35 regions, respectively, in which DUH1 and DUH3 are autosomaldominant, while DUH2 is an autosomal recessive. 8 ABCB6 and SASH1 are reported to be the pathogenic genes related to DUH. [7][8][9][10][11][12][13][14][15][16] Although Wu et al 10 maintained that the DUH phenotypes caused by ABCB6 mutations showed more generalized mottled hyperpigmented macules mixed with hypopigmented macules arranged in a reticular pattern; however, the DUH phenotypes caused by SASH1 mutations are more likely to be confused with generalized lentiginosis.…”

mentioning

confidence: 99%

“…8 ABCB6 and SASH1 are reported to be the pathogenic genes related to DUH. [7][8][9][10][11][12][13][14][15][16] Although Wu et al 10 maintained that the DUH phenotypes caused by ABCB6 mutations showed more generalized mottled hyperpigmented macules mixed with hypopigmented macules arranged in a reticular pattern; however, the DUH phenotypes caused by SASH1 mutations are more likely to be confused with generalized lentiginosis. However, Cao et al pointed out that although in the same family, the same mutation of SASH1 were shown in all of the affected individuals including the proband, nevertheless, the clinical manifestations among the affected individuals were different.…”

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confidence: 99%

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Retyping and molecular pathology diagnosis of dyschromatosis universalis hereditaria

Zhou

Yang

Chen

2023

Experimental Dermatology

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Dyschromatosis universalis hereditaria (DUH) is characterized by diffuse symmetrically distributed hypopigmented macules mixed with hyperpigmentation. DUH is divided into three types by Online Mendelian inheritance in man (OMIM) that is, DUH1 (OMIM 127500), DUH2 (OMIM 612715) and DUH3 (OMIM 615402) according to the different linkage regions. Although each condition possesses corresponding phenotypic characteristics and the prognosis for each is somewhat different, these disorders are highly overlapped and difficult to differentiate in the clinical setting. Our latest study reveals a novel DUH subtype that presents a mild phenotype of pigmentation anomalies and is named PER3rs772027021 SNP related DUH or DUH4 by us, which make the DUH subtype can be further retyped. Heterozygous distribution or mosaic‐like distribution of melanin is a newly discovered pathological features that is uniquely demonstrated in the affected layers of DUH1 and DUH4 patients. In this review, DUH is further divided into four subtypes according the causative genes and their mutational sites, and the mutation regions described in the previous reports. To make an accurate diagnosis, we suggest that Sanger sequencing or the target region sequencing (TRS) to the candidate causative genes related melanogenesis may be the most effective and convenient method of clinical diagnosis or/and prenatal diagnosis for DUH and DUH‐like patients. More importantly, heterozygous distribution or mosaic‐like distribution of melanin can be utilized for differential diagnosis of DUH. We also investigate the underlying molecular mechanism to form mosaic‐like melanin in the affected layers of hyper‐ and/or hypo‐pigmented macules from DUH1 and DUH4 patients. This review provides a molecular and pathological delineation of four types of DUH and aims to establish a concise diagnostic strategy to allow clinical dermatologists to make an accurate diagnosis.

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Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria

Cited by 10 publications

References 26 publications

The PER3rs772027021 SNP induces pigmentation phenotypes of dyschromatosis universalis hereditaria

The PER3rs772027021 SNP induces pigmentation phenotypes of dyschromatosis universalis hereditaria

Uncovering a new SASH1 mutation associated with dyschromatosis universalis hereditaria using whole-exome-sequencing: A case report

Retyping and molecular pathology diagnosis of dyschromatosis universalis hereditaria

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