Abstract Hereditary cylindromatosis (HC; MIM 132700) is an autosomal dominant condition characterized by be- nign skin appendage tumors most commonly on the scalp and face. Previously, the HC gene (CYLD1) was linked to chromosome 16q12–13, and tumors showed loss of het- erozygosity (LOH), suggesting that CYLD1 is a tumor suppressor gene. Here we report a new multi-generation cylindromatosis family whose condition maps to that re- gion, with 7/13 tumors showing LOH on 16q. Hereditary cylindromatosis (HC) is a rare autosomal dom- inant disease characterized by the development of benign tumors of skin appendages, including hair follicle (e.g., trichoepitheliomas), eccrine gland (e.g., eccrine spirade- nomas), apocrine gland (e.g., cylindromas), and seba- ceous gland (e.g., sebaceous epitheliomas). In addition to their occurrence in HC, these tumors may also occur spo- radically and can be disfiguring and painful. Patients with HC usually begin to develop tumors by early adulthood, although there is variable expression, and some patients may be affected at a younger age (Gerretson et al. 1995). These tumors most often grow on the face and scalp, with the back and chest also frequently being involved (van Balkom and Hennekam 1994; Gerretson et al. 1995). When the tumors cover the scalp, the condition is often referred to as the turban tumor syndrome. Previously, the gene responsible for HC (CYLD1) was linked to chromosome 16q12–13 (Biggs et al. 1995), be- tween D16S411 and D16S416, by using data from two families. In addition, Biggs et al. (1995, 1996) found loss of heterozygosity (LOH) of the wild-type allele in tumors, spanning most of 16q with no LOH being found in 16p. This suggested that CYLD1 is a tumor suppressor gene that follows the classic two-hit model (Knudson 1971). Verhoef et al. (1998) reported a Dutch family also linked to CYLD1 and in which three tumors showed LOH at one non-recombinant marker (no further tumor analysis was performed). In addition, 16q LOH has been observed in sporadic HC tumors, suggesting that the same gene is in- volved in both familial and sporadic forms (Biggs et al. 1996). Here, we report a new HC family whose condition ap- pears to be caused by CYLD1 and whose tumors show LOH in the same region. This further supports localization of CYLD1 at 16q12–13 and suggests that somatic mutations (presumably deletions) in HC tumors have common break- points. The family is represented in Fig. 1. After evalua- tion by genetics and pathological analysis of tumor speci- mens, HC was diagnosed in individuals denoted by solid symbols. Individual II-1 is 60 years old, with tumors so numerous on her scalp as to be confluent. Her face is also severely affected, but only sparse tumors reside on trunk and limbs. The tumors, which began appearing in child- hood, are 0.5–3.0 cm in diameter, with a small percentage being painful to touch. No signs of malignancy have been found. Individual III-2 is 38 years old and has several dozen small tumors, predominantly on his scalp. His son (IV-1, aged 12) has had one small eyelid tumor, which pathological analysis showed to be a trichoepithelioma. To test for an association of the HC gene in this family with the CYLD1 16q12–13 region, DNA was extracted from blood and tumor samples as previously described (Colman et al. 1995). Standard radioactive polymerase- chain-reaction-based genotyping of chromosome 16 mi- crosatellite markers was carried out as described previ- ously (Colman et al. 1995), by using the recommended annealing temperatures (Research Genetics). The marker segregation among the family members, including a num- ber of consecutive non-recombinant markers, is shown in Susanne A. M. Thomson · Sonja A. Rasmussen · Jun Zhang · Margaret R. Wallace A new hereditary cylindromatosis family associated with CYLD1 on chromosome 16 Hum Genet (1999) 105 : 171–173 © Springer-Verlag 1999 Digital Object Identifier (DOI) 10.1007/s004399900077 Received: 2 April 1999 / Accepted: 29 April 1999 / Published online: 28 June 1999 SHORT REPORT S. A. M. Thomson · S. A. Rasmussen · J. Zhang · M. R. Wallace Division of Genetics, Department of Pediatrics, Center for Mammalian Genetics, University of Florida College of Medicine, Gainesville, Fla., USA M. R. Wallace (✉) Pediatric Genetics, Box 100296, University of Florida, Gainesville, Fl 32610–0296, USA e-mail: peggyw@cmg.health.ufl.edu, Tel.: +1 352 392 4104, Fax: +1 352 392 3051