CYLD皮肤综合征(CCS;syn。Brooke-Spiegler综合征)是一种罕见的常染色体显性遗传性疾病,其特征是多发性附件皮肤肿瘤,包括圆柱瘤,螺旋腺瘤,和毛发上皮瘤.在CCS中已经报道了超过100个圆柱形瘤(CYLD)基因的种系突变,其中大多数是移码突变或小改变。
我们发现了一个大的,拥有CCS的三代中国家庭,由18个活着的家庭成员组成,包括六个受影响的人。为了探索这个家族的分子生物学,我们进行了靶向下一代测序和AffymetrixCytoScanHDSNP阵列,以分析CYLD基因的突变.
一个新的大缺失突变,NC_000016.9:g。在该家族的先证者中发现了(50826498_50827517)_(50963389-50967346)del。这种缺失导致CYLD基因的近140kb片段丢失,跨越外显子17~20,代表泛素特异性蛋白酶结构域的编码区。进一步的定量聚合酶链反应证明,所有患者和两个与先证者相关的家庭成员都带有这种大的缺失。
我们的研究扩展了CCS中突变的类型,无疑将为受这种情况影响的家庭提供遗传咨询的有价值的信息。
CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) is a rare autosomal dominant hereditary disease characterized by multiple adnexal skin tumors including cylindromas, spiradenomas, and trichoepitheliomas. More than 100 germline mutations of the cylindromatosis (CYLD) gene have been reported in CCS and most of them are frameshift mutations or small alterations.
We identified a large, three-generation Chinese family with CCS, which consisted of 18 living family members, including six affected individuals. To explore the molecular biology of this family, we carried out targeted next-generation sequencing and Affymetrix CytoScan HD SNP array to analyze the mutation in the CYLD gene.
A novel large deletion mutation, NC_000016.9:g.(50826498_50827517)_(50963389-50967346)del was found in the proband of this family. This deletion results in the loss of a nearly 140 kb fragment of the CYLD gene, spanning exons 17 ~ 20, which represent the coding regions of the ubiquitin-specific protease domain. Further quantitative polymerase chain reaction proved that all patients and two proband-related family members carried this large deletion.
Our study expands the types of mutations in CCS and will undoubtedly provide valuable information for genetic counseling for families affected by the condition.