Identification of one novel mutation of the NCSTN gene in one Chinese acne inversa family

Acne inversa (AI; OMIM 142690) is an autosomal dominantly inherited skin disorder. Clinically, AI is characterized by painful deep-seated, inflamed lesions in the apocrine gland-bearing area of the body, especially in the axillary, inguinal, and anogenital regions. To date, three genetics regions (6q25.1–25.2, 19p12–19q12, and 1p21.1–1q25.3) have been identified by linkage analysis to be responsible for AI.1,2 A total of 21 mutations have been identified in the g-secretase genes including PSENEN (19q13.12, NM_172341), PSEN1 (14q24.3, NM_000021), andNCSTN (lies within the previously reported region, 1q22–q23, NM_015331) genes.3 Here, we performed a DNA direct sequencing in two AI families of Chinese Han and identified one novel mutation of the NCSTN gene. Two AI autosomal dominant multiplex kindred families (Figure 1A and B) and 100 unrelated healthy controls were recruited in our study. The proband of Family 1 is an 18-year-old boy who presented with a 4-year history of inflammatory papules, painful nodules, pustules, abscesses, and hypertrophic scar throughout the armpits, buttocks, and groin, especially on the neck (Figure 1C). The proband of Family 2 is a 57-year-old man with a 35-year history of painful nodules, pustules, abscesses, and hypertrophic scar, with these lesions spread over the trunk, limbs, armpits, and buttocks (Figure 1D). Other affected individuals of the two families suffered similar symptoms and all of them met the diagnostic criteria of AI.4 Apart from the asterisk-marked individual in Family 2, where the disease was accompanied by psoriasis, no other disorders were observed. Written consent was obtained from all the individuals and the study was approved by the ethics committee of Shandong Provincial Institute of Dermatology and Venereology. We collected venous blood from 17 triangle-marked family members (Figure 1A and B), including two affected members and two unaffected members in Family 1 and five affected members as well as eight unaffected members in Family 2. DNA was extracted from venous blood using a blood DNA kit (OMEGA Bio-Tek, Norcross, GA, USA). All coding exons including intron–exon boundaries of NCSTN (17 exons), PSEN1 (10 exons), and PSENEN (3 exons) were amplified by PCR using specific primers. After the purification of PCR products, direct sequencing was performed in all the 17 participants and 100 healthy controls using ABI 3130xl Genetic Analyser (Applied Biosystems, Foster City, CA, USA). Those sequences showing suspicious variation would be validated by reverse sequencing.