Identification of a Novel Mutation in SASH1 Gene in a Chinese Family With Dyschromatosis Universalis Hereditaria and Genotype-Phenotype Correlation Analysis

Wu, Nan; Tang, Lili; Li, Xiuxiu; Dai, Yuwei; Zheng, Xiaodong; Gao, Min; Wang, Peiguang

doi:10.3389/fgene.2020.00841

Cited by 12 publications

(21 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, 17 heterogeneous missense mutations in SASH1 have been confirmed to be associated with pigmentation disorders, among which eight mutations result in DUH [ 5 , 11 , 12 ] and nine are responsible for multiple lentiginous phenotypes [ 13 – 16 ]; furthermore, the missense mutation c.1849G>A was reported to result in a loss of pigmentation with palmoplantar keratoderma and skin carcinoma [ 17 ]. The distribution of all mutations in the protein domain of SASH1 inducing pigmentary anomalies is shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Analysis revealed the presence of the c.1784T>C (p.M595T) and c.1651T>C (p.Y551H) missense mutations in the SASH1 gene. The most recent case was described by Wu et al [ 12 ], who described the case of a 6-year-old girl with generalized hyperpigmented spots, and her family members shared similar symptoms. After genetic analysis, a novel missense mutation, c.1553A>C, was discovered.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a novel missense mutation in ABCB6 (p.N467S) was reported in a case of xeroderma pigmentosum C combined with DUH-like pigmentation [ 26 ]. Wu et al [ 12 ] pointed out that, compared with the disease caused by SASH1 mutation, the disease caused by ABCB6 mutation showed more typical manifestations, such as generalized mottled hyperpigmented macules mixed with hypopigmented macules arranged in a reticular pattern. In contrast, diseases caused by SASH1 mutations are more likely to be confused with generalized lentiginosis.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2021

View full text Add to dashboard Cite

Background Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. Methods Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations. Results A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6. Conclusion Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2021

View full text Add to dashboard Cite

show abstract

“…SASH1 is a gene containing 20 exons that maps to chromosome 6q24.3 and encodes sterile alpha motif‐ and SH3 domain‐containing protein 1 (Figure 3A). 8‐16 SASH1 is expressed in many human tissues including cultured human epidermal keratinocytes, dermal fibroblasts, and melanocytes in the skin 16 . SASH1 is also a candidate tumor suppressor gene, 17 which regulates TLR4 signaling through its formation of a molecular complex with TRAF6 18 .…”

Section: Introductionmentioning

confidence: 99%

“…To date, only 14 mutations have been reported in SASH1 gene (Table 1). Eleven of the heterozygous variations are located in the SLY domain 9‐12,14,15 , and two in the SH3 domain 14,15 have followed an autosomal dominant inheritance pattern and led to pigmented dermatosis. Only one homozygous mutation in SASH1 in a family showed an autosomal recessive inheritance pattern and this was characterized by dyschromatosis, alopecia, palmoplantar keratoderma, ungueal dystrophy, teeth abnormalities, and a predisposition to spinocellular carcinomas 16 .…”

Section: Introductionmentioning

confidence: 99%

Two novel SASH1 mutations in Chinese families with dyschromatosis universalis hereditaria

Liu

Habulieti

Wang

et al. 2021

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Background Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis characterized by hyper‐ and hypo‐pigmented macules on the face, trunk, and extremities. The condition causes severe cosmetic problem which can lead to significant psychological distress to the patients and bear a negative impact on society. DUH is a condition with genetic heterogeneity. The SASH1 gene was recently identified as pathogenic genes in DUH patients. Methods Two families clinically diagnosed with dyschromatosis universalis hereditaria were enrolled. Whole‐exome sequencing combined with Sanger sequencing and bioinformatics analysis was performed in the probands. MutationTaster, CADD, SIFT, PolyPhen‐2, and LRT software, and The American College of Medical Genetics and Genomics Standards and Guidelines were employed to assess the pathogenicity of detected missense mutations. One hundred healthy unrelated Chinese individuals were used as controls. All participants signed an informed consent form. Results Genetic screening revealed a heterozygous SASH1 c.1547G>A (p.Ser516Asn) mutation for patients in family 1, and SASH1 c.1547G>T (p.Ser516Ile) for family 2. Both such de novo mutations are located in a highly conserved SLY domain in SASH1, have not been previously reported in any publication, and were not detected in any control databases. Conclusions The novel heterozygous mutations, SASH1 c.1547G>A and c.1547G>T, are likely responsible for the DUH phenotype in these two families. Our study expands the mutation spectrum of DUH. Whole‐exome sequencing showed its efficiency in the diagnostic of hereditary skin disorders.

show abstract

The PER3rs772027021 SNP induces pigmentation phenotypes of dyschromatosis universalis hereditaria

Chen

Yang

et al. 2023

J Mol Med

View full text Add to dashboard Cite

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.

show abstract

Identification of a Novel Mutation in SASH1 Gene in a Chinese Family With Dyschromatosis Universalis Hereditaria and Genotype-Phenotype Correlation Analysis

Cited by 12 publications

References 28 publications

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

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

Two novel SASH1 mutations in Chinese families with dyschromatosis universalis hereditaria

The PER3rs772027021 SNP induces pigmentation phenotypes of dyschromatosis universalis hereditaria

Contact Info

Product

Resources

About