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Growing evidence suggests that some individuals may exhibit symptoms of dependence to ultraviolet light, a known carcinogen, in the context of tanning. Genetic associations with tanning dependence (TD) have not yet been explored. We conducted an exome-wide association study in 79 individuals who exhibited symptoms of TD and 213 individuals with volitional exposure to ultraviolet light, but who were not TD based on three TD scales. A total of 300 000 mostly exomic single nucleotide polymorphisms primarily in coding regions were assessed using an Affymetrix Axiom array. We performed a gene burden test with Bonferroni correction for the number of genes examined (P 0.05/14 904 = 3.36 × 10(-6) ). One gene, patched domain containing 2 (PTCHD2), yielded a statistically significant P-value of 2.5 × 10(-6) (OR = 0.27) with fewer individuals classified as TD having a minor allele at this locus. These results require replication, but are the first to support a specific genetic association with TD.

Nevus sebaceus (NS) is a congenital skin hamartoma that presents in childhood. Tumors may arise within these lesions over time. Mutations in the PTCH gene have been associated with both NS and some of the developing tumors. Only nine documented cases of basal cell carcinoma arising in nevus sebaceus in childhood are available. We present a case of an 8-year-old male with nevus sebaceus who developed a basal cell carcinoma. Evaluation for constitutional PTCH gene mutation and loss of heterozygosity (LOH) from the BCC within the NS did not reveal an underlying mutation. We further discuss the literature regarding prophylactic excision of NS.

Objective: To explore the role of MTNR1B rs10830963 and G6PC2 rs560887 variants in the pathogenesis of impaired fasting glucose (IFG) in obese adolescents. Methods: A total of 346 Caucasians, 218 African-Americans, and 217 Hispanics obese children and adolescents underwent an oral glucose tolerance test (OGTT) and 518 underwent the evaluation of insulin secretion by the oral minimal model (OMM). Also, 274 subjects underwent a second OGTT after 3.0 -/+ 2.1years. Results: The MTNR1B rs10830963 variant was associated with higher fasting glucose levels and lower dynamic beta-cell response in Caucasians and Hispanics (P 0.10). Conclusions: It has been shown for the first time in obese youth that the MTNR1B variant is associated with an increased risk of IFG. (Less)

Gorlin's syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by a familial or hereditary predisposition to basal cell carcinomas (generally multiple and of early onset), odontogenic keratocysts (jaw cysts), palmar and plantar pits, a wide variety of developmental defects, as well as cancers such as medulloblastomas and ovarian fibromas. The gene for NBCCS has been mapped to human chromosome region 9q22.1-q31 by linkage analysis and by cytogenetic evidence of deletions in this region in patients with the syndrome. This is supported by loss of heterozygosity in tumors of polymorphic marker loci flanked by D9S197 and D9S180. We have utilized sequence tagged site (STS) mapping and somatic cell hybrid panel analysis to construct two overlapping yeast artificial chromosome (YAC) contigs spanning this region of the genome. We used the YAC contigs to identify a new zinc finger gene containing a highly informative microsatellite locus.

The Fourth International Workshop on Chromosome 9 was a highly successful endeavor in terms of the growth of the map, both genetic and physical, the amount of data entered into GDB, and the continued comradeship in the sharing of data and resources that was exemplified. SIGMA remained a stable and valuable part of the chromosome 9 mapping effort. A new subsection outlining the morbid anatomy of chromosome 9 was included. Finally, specific goals were set for the community to aim for over the upcoming months. These included extending the information about the ease of use of genetic markers, and coordinating across numerous groups the meiotic breakpoint mapping of many microsatellite markers. Workshop files are available by anonymous ftp from ftp.gene.ucl.ac.uk (128.40.82.1) in the subdirectory /pub/c9workshop/1995, or by using a World Wide Web browser (such as Mosaic or Netscape) via the Chromosome 9 Home Page (at the URL http:www.gene.ucl.ac.ukchr9home.html). Copyright © 1995, Wiley Blackwell. All rights reserved

Hereditary cutaneous malignant melanoma (HCMM) with or without atypical moles has been described in several large kindreds worldwide. Despite numerous studies of these kindreds, the gene or genes responsible for this disorder has not yet been identified. Cytogenetic and molecular studies of melanoma tumor tissue and cell lines suggest that a gene involved in the pathogenesis of malignant melanoma lies on chromosome 9p. We describe a woman with atypical moles and multiple primary melanomas, who lacks a family history of HCMM, and, has a de novo constitutional unbalanced reciprocal translocation involving the short arms of chromosomes 5 and 9 with a cytogenetically visible deletion of 5p or 9p: [46,XX,-5,-9, +der(5)t(5;9) (p13.3 or 14.2;p13.3 or 21.2), +der(9)t(5;9)]. This finding supports the hypothesis that a gene predisposing to HCMM lies on the short arm of chromosome 9. © 1993 Wiley-Liss, Inc.

Ann. Hum. Genet. (1992), 56, 167-221 Printd in &eat Britain REPORT on the First International Workshop on Chromosome 9 held at Girton College Cambridge, UK, 22-24 March, 1992 Prepared by: S. POVEY, M. SMITH, J. HAINES, D. KWIATKOWSKI, J . FOUNTAIN, A. BALE, C. ABBOTT, I. JACKSON, M. LAWRIE and M. HULTEN The meeting was attended by 70 participants whose names and addresses are included in an appendix t o this report. Fifty-four abstracts were received and the data presented on posters. The main role of the meeting was seen as the construction of a consensus map of chromosome 9, together with a sharing of knowledge about resources such as hybrids, libraries and new polymorphisms. The group divided into separate working parties t o consider 9p, 9cen-9q32, 9q33-9qter, global problems and comparative mapping. The findings of each of these groups are included in this report. There was a separate discussion of resources which is also summarized. Two databases were discussed and demonstrated (GDB by Bonnie Maidak and ldb by Andy Collins). The chromosome 9 workshop was preceded on the afternoon of Sunday, 22 March by a workshop on Tuberous Sclerosis. Because of the relevance of this to chromosome 9q34 a report on this workshop is included in that section. A further subgroup met on 24 March t o discuss the CEPH chromosome 9 consortium map and a brief report on their progress was produced. In accordance with the recommendation of the Global group an attempt has been made to reference information in the maps but it is recognized that this is incomplete. Within the text of this report a name without a date refers to an abstract a t this meeting (see end of report). A name with a date refers t o a publication listed in the references and these are generally confined to very recent or in press references. A verbal communication at the meeting is identified as a personal communication. For authoritative referencing of published information the reader should consult GDB. It is also planned t o enter information into ldb so that in future it may be possible to compare a map produced by artificial intelligence with that produced by a human consensus view ! It was decided to hold a further workshop on chromosome 9 in April or May 1993 and David Kwiatkowski kindly agreed to organize this in Boston. CHROMOSOME 9p A number of groups co-ordinated by Jane Fountain combined to produce a n ordered map of 9p (Figs 1, 2 ) . This incorporates a partial map of 9p supported by multipoint linkage analysis, pulsed field gels and FISH (Fountain et al. and Fountain et al. 1992). Most of the detailed information on 9p comes from intensive effort by several workers to investigate the position of a potential tumour suppressor gene or genes in gliomas, leukaemias, non-small cell lung carcinomas (NSCLCs) and melanomas. Deletion mapping combined with isolation of the region on a 900 kb YAC contig has led to the determination of the physical position of 27 human interferon genes (Ilia2 et al., Olopade et al.). The position of WP4 remains uncertain. From the minimal region of overlap of an extensive series of deletions in leukaemias and gliomas Olopade et al. suggested the existence of a tumour suppressor gene between the proximal end of IFNA and the gene MTAP. Other groups also reported results consistent with this (Nobori et al., Middleton et al., Heyman et al.). I2 H G E 56

Objectives and Study Design: Squamous cell carcinomas are common malignancies and a major cause of mortality. The molecular mechanisms involved in tumorigenesis remain largely unknown, but sequence alterations have been identified in coding regions of several genes. Primary squamous cell carcinomas of various tissues (skin, head and neck, esophagus, lung, penis, uterus, and vagina) from 52 patients were analyzed for the presence of mutations within several candidate genes presumably involved in tumorigenesis: Gsα, Gi2α, GTPase activating protein (GAP), and patched (PTCH) genes. Methods: Mutational analysis scheme included polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE), single stranded conformational polymorphism (SSCP), and selected sequence analysis. Results and Conclusion: No tumor had any evidence of mutations in any of these analyzed genes. Mutations within these genes do not occur frequently in an unselected population of patients with squamous cell carcinomas.

Because linkage has been reported between HLA and the locus for hereditary ataxia in some families, we studied a 3-generation kindred in which several individuals had dominantly inherited spinopontine atrophy. Affected family members had upper and lower limb ataxia, hypoactive reflexes, loss of proprioception, dysarthria, dysphagia, and pronounced extraocular movement abnormalities. Linkage analysis, based on 25 markers in 28 people, gave strongly negative results with both HLA (z less than -2.0 for theta less than 0.15) and GLO1 (z less than -2.0, theta less than or equal to 0.01). The highest LOD score was for linkage to GPT on chromosome 16 (z = 0.42, theta = 0.0). To assess the relationship between HLA linkage and phenotype, 4 published kindreds with adequate clinical and neuropathological descriptions were used for comparison to the present family. Persons in the 3 families showing evidence for HLA linkage had clinical and pathologic changes consistent with olivopontocerebellar atrophy, type 1. The conditions in the 2 "nonlinked" families were phenotypically distinct from the HLA-linked condition with respect to extraocular movement findings and peripheral sensory nervous system signs. They differed markedly from each other in neuropathologic changes.

Most reported cases of Sotos syndrome are sporadic, but autosomal dominant and recessive inheritance patterns have been suggested. Ascertainment of a two-generation family through a 7-year-old proposita with a learning disability allowed the relatively unbiased study of two affected relatives. Developmental delay was not pronounced in the patient's mother or sister; craniofacial characteristics at variance with the characteristic description included acrocephaly and maxillary prominence. Steepness of the anterior cranial base angle and protrusion of the middle and lower face, shown in all three patients by cephalometric radiographs, deserve further evaluation as diagnostic criteria.