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Advances in dermatology and venereology Acta Dermato-Venereologica
A Novel De novo Mutation of the SASH1 Gene in a Chinese Family with Multiple Lentigines
Jianbo WANG 1, 2 #, Jia ZHANG 3 #, Xueli LI 1, 2, Zhexin WANG 4, Dongchun LEI 1, 2, Guofang WANG 1, 2, Jianguo LI 1, 2, Shoumin ZHANG 1, 2, Zhenlu LI 1, 2 * and Ming LI 3 * Departments of Dermatology, 1 Henan Provincial People’ s Hospital, No. 7 Weiwu Road, Zhengzhou 450003, Henan, 2 Zhengzhou University People’ s Hospital, Zhengzhou, Henan, 3 Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, and 4 Kaifeng Second People’ s Hospital, Kaifeng, Henan, China. * E-mail: aypyslm @ 163. com; lizhenlu @ sohu. com
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These authors contributed equally to this paper. Accepted Nov 10, 2016; Epub ahead of print Nov 14, 2016
Lentigines are flat or slightly raised, small, black-brown macules with a clearly defined edge( 1). Histologically, increased numbers of melanocytes and elevated amounts of melanin can be observed. In some conditions, lentigines are associated with multisystem syndromes, which usually present symptoms at birth or early childhood, such as Peutz-Jeghers syndrome, Noonan syndrome and LEOPARD syndrome( 1 – 4).
SASH1 is a member of the SLY-family of signal adapter proteins, and serves as a candidate tumour suppressor in breast and colon cancer( 5, 6). Heterozygous SASH1 mutations were initially reported to be associated with dyschromatosis universalis hereditaria( DUH), which is predominantly characterized by generalized mottled hyper- and hypo-pigmentation( 7).
Recently, several cases of SASH1-related lentiginous phenotype have been reported in succession( 8 – 10). This report describes the clinical and molecular delineation of a Chinese family with multiple lentiginous phenotypes, and the successful treatment of facial lentigines with a 755-nm Q-switching alexandrite laser.
CASE REPORT
This study was approved by the Institutional Review Board of Henan Provincial People’ s Hospital, Henan, China, and was conducted in accordance with the principles of the Declaration of Helsinki. After obtaining written consent, the proband, his parents, his grandparents and 100 ethnic-matched healthy controls were indexed in this study.
The proband is a 27-year-old man from Henan Province, China, who was referred to our department in June 2015 with multiple“ freckles” on the forehead since 18 months of age. The lesions gradually increased and spread to the patient’ s entire body by the age of 10 years. Dermatological examination revealed multiple lentigines on the trunk, limbs and face( Fig. 1). His mother has a similar lentiginous phenotype. No mental abnormalities, facial malformation, or cardiac defects were present in the patient or his mother.
Peripheral blood samples from the indexed subjects were collected for molecular analysis. Genomic DNA was extracted using TIANamp Blood DNA Kit( Tiangen Biotech, Beijing, China). Primers flanking all coding regions of SASH1 were designed using software Primer Premier 5.0( Premier Biosoft International, Palo Alto, CA, USA). The extracted genomic DNA samples were amplified by PCR. Purified PCR products were sequenced directly using an Abi Prism ® 3730 automated sequencer( Applied Biosystems, Foster City, CA, USA). Mutation was described by comparison with the NCBI cDNA reference sequence: NM _ 015278.3.
A novel heterozygous missense mutation c. 1519T > G( p. Ser507Ala) in SASH1 was identified in the proband and his affected mother. Moreover, mutation p. Ser507Ala was not identified in his unaffected father, his grandparents or in 100 normal controls( Fig. S1 1). This is a de
1 https:// www. medicaljournals. se / acta / content / abstract / 10.2340 / 00015555-2575
Fig. 1. Clinical picture of the proband with SASH1 mutation.( a) Multiple lentigines on the face.( b) Facial appearance after treatment with a 755 nm Q-switching alexandrite laser.( c) Multiple lentigines on the trunk and limbs. A written permission is given by the patient to publish these photos. doi: 10.2340 / 00015555-2575 Acta Derm Venereol 2017; 97: 530 – 531
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica.