gamma-Secretase Gene Mutations in Familial Acne Inversa

g-Secretase Gene Mutations in Familial Acne Inversa

Baoxi Wang,^1,* Wei Yang,^2,* Wen Wen,^3,* Jing Sun,^2,* Bin Su,^1,* Bo Liu,⁴ Donglai Ma,¹ Dan Lv,² Yaran Wen,² Tao Qu,¹ Min Chen,⁵ Miao Sun,² Yan Shen,^2,+ Xue Zhang^{2,3, +}

Published Online October 7, 2010
Science DOI: 10.1126/science.1196284

Acne inversa (AI), also known as hidradenitis suppurativa, is a chronic, recurrent, inflammatory disease of hair follicles that often runs in the family. We studied six Chinese families with features of AI as well as additional skin lesions on back, face, nape, and waist, and found independent loss-of-function mutations in PSENEN, PSEN1, or NCSTN, the genes encoding essential components of the -secretase multiprotein complex. Our results identify the -secretase component genes as the culprits for a subset of familial AI, implicate the -secretase-Notch pathway in the molecular pathogenesis of AI, and demonstrate that familial AI can be an allelic disorder of early-onset familial Alzheimer's disease.

¹ Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
² State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS & PUMC, Beijing, China.
³ China Medical University, Shenyang, China.
⁴ Chinese National Human Genome Center at Beijing, Beijing, China
⁵ Institute of Dermatology, CAMS & PUMC, Nanjing, China.

^* These authors contributed equally to this work.

+To whom correspondence should be addressed.