简介：AbstractObjective:Isolated hereditary hypotrichosis is caused by mutations in as many as 11 different genes. The conventional mutation detection strategy consists of sequencing of individual candidate genes separately, a time consuming and costly approach. In this study, we perform genome-wide single nucleotide polymorphism (SNP) array to identify candidate genes of hereditary hypotrichosis.Methods:A consanguineous family with two patients with hereditary hypotrichosis was enrolled, and autozygosity mapping by genome-wide SNP array was utilized to identify candidate genes.Results:Autozygosity mapping delineated runs of homozygosity, and alignment of the 11 genes identified the hairless (HR) gene as the candidate gene. Nucleotide sequencing revealed a novel homozygous mutation c.381delT, p.Ser127ArgfsTer40.Conclusion:This study illustrates how autozygosity mapping by a high-density SNP array streamlines mutation detection in heritable skin diseases.

简介：AbstractObjective:Well-defined germ-line mutations in the PTCH1 gene are associated with syndromic multiple basal cell carcinomas (BCCs). Here, we used whole exome sequencing (WES) to identify the role of patched-1 in patients with multiple, unusually large BCCs.Methods:A 72-year old patient presenting with numerous BCCs progressing to large ulcerating lesions was enrolled. WES was used to identify the pathogenic gene locus.Results:Genetic work-up by WES identified a homozygous PTCH1 nonsense mutation in the tumor tissue but not present in her blood cells or in non-lesional skin. In addition, heterozygous missense mutations were identified in three cancer-associated genes (EPHB2, RET, and GALNT12) in blood cells as well as in lesional and non-lesional skin. We also tested systemic immune therapy as a potentially beneficial approach to treat patients with numerous large BCCs on scatted areas of involvement. A rapid and sustained response to nivolumab was noted, suggesting that it is an efficacious drug for long-term therapeutic outcome.Conclusion:PTCH1, EPHB2, RET, and GALNT12 may potentially contribute to the synergistic oncogene driven malignant transformation manifesting as multiple, unusually large BCCs.