p =0.006; and femoral neck BMD, rs16948767 (females only, MAF = 0.008), p = 0.004. There was no association between the promoter polymorphisms and fracture, but an association was observed with femoral neck BMD in females (p = 0.035). Conclusion: We have identified several novel genetic variants within the COL1A1 gene which are associated with osteoporosis- related phenotypes, distinct from those previously identified. This study confirms that genetic variation at the COL1A1 locus predisposes to osteoporosis, but further functional studies will be required to uncover the molecular basis of these associations. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.150 P239 Adenoma of parathyroid gland in a woman with basal cell carcinoma syndrome I. Zofkova a, *, M. Kuklik b a Department of Clinical Endocrinology, Institute of Endocrinology, Prague 1, Czech Republic b Department of Biology and Genetics, 2nd Medical Faculty, Charles University, Prague 5, Czech Republic Naevus basal cell carcinoma syndrome (NBCCS) (Gorlin–Goltz syndrome) is an autosomal dominant multisystem disease mani- fested by a number of abnormalities together with multiple basal cell carcinomata and an increasing tendency to various other neoplastic lesions. Coincidence of NBCCS with adenoma of para- thyroid gland is not usual. The only such case has been described in a man by Fathizadeh in 1980. We observed this coincidence in a 50- year-old white woman with multiple stigmas (macrocephaly, caput quadratum and gothic palate, multiple tooth agenesis and retentions in her youth). Hysterectomy for myomatosis and operations for multiple basaliomas at the regions of the head, neck and shoulders were performed later in her life. Chromosomal investigation demonstrated normal female karyotype 46XX with the frequency of breakages 1 case of 100 mitosis. The gene for NBCCS was localized at chromosome 9q according to the method described by Reis et al. (1992). Serum ionized calcium in our patient was 1.35 mmol/l. Circulating PTH values (71 ng/l) exceeded the upper limit of normal range (up to 55). The marker of bone resorption – urinary deoxypyridinoline – was markedly elevated as well (11.1 nmol/mmol creatinine, normal range up to 6.5), however no bone syndrome was observed in our patient. An isotope scan of parathyroid glands using 99mTc-MIBI showed the early and late accumulation of the isotope in a round deposit on the left side of the jugulum. The diagnosis of parathyroid adenoma was subsequently confirmed histologically after parathyr- oidectomy revealing superiority of chief cells, arranged mainly follicularly. The pedigree of the patient's family indicates multiple occurence of NBCCS. The patient's two daughters (21 and 27-year olds), born from different marriages, have also been afflicted with the syndrome. None of them, however, displayed any clinical or biochemical symptoms of hyperparathyroidism to date. Conclusion: The case reported here, is noteworthy for the unusual case of parathyroid adenoma in a subject with extremely rare NBCCS. Although incidental occurence of primary hyperparathyroidism cannot be excluded in this postmenopausal woman, a common pathogenetic mechanism of both these diseases seems to be plausible. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.151 P240 Distinct OI phenotype caused by COL1 C-proteinase site mutations A.M. Barnes a , K. Lindahl b , M.P. Whyte c , T. Hefferan d , C. Rubin b , A. Kindmark b , W. McAlister c , S. Mumm c , O. Ljunggren b , J.C. Marini a, * a Bone and Extracellular Matrix Branch, NICHD, NIH, Bethesda, USA b Department of Endocrinology, Uppsala University, Uppsala, Sweden c Center for Metabolic Bone Disease and Molecular Research, Shriner's Hospital for Children, St. Louis, USA d Department of Orthopedics, Mayo Clinic, Rochester, USA Osteogenesis imperfecta (OI), or brittle bone disease, is often caused by mutations in the type I collagen genes; over 800 have been described. Mutations in type I procollagen C-propeptide cleavage site are of particular interest because they disrupt a unique processing step. We identified two children with mild OI who had cleavage site mutations in COL1A1 (P1: α1(I)Asp1041Asn) or COL1A2 (P2: α2(I) Ala1029Thr). Clinical features, including BMD, histomorphometry and radiographs, were compared to collagen modification, chain incorporation and procollagen processing in fibroblasts. P1 had a normal LRP5 sequence. P1 DEXA Z-score and pQCT vBMD were +3, contrasting with radiographs demonstrating osteopenia and os-in-os vertebrae, and histomorphometry revealing increased bone remodel- ing, without a mineralization defect or signs of osteoschlerosis. P2 had a DEXA z-score of 0, gracile long bones with radiographic osteopenia, and decreased BV/TV and increased BFR without a mineralization defect on histomorphometry. Both P1 and P2 are at the 75th percentile for height. The dermal fibrils of P1 had a normal diameter with a smooth surface, while P2 had small fibrils including some with blebs. Steady-state collagen electrophoresis showed slight backstreaking of α1(I) and α2(I) in cell layers of both probands. The baseline of P1 chains was delayed, while those of P2 migrated normally. Chain incorporation was normal in P1 and slightly delayed in P2. Pericellular processing of P1 was delayed, with increases in both pCα1 and proα2, while P2 had increased pCα2 and proα2 and normal processing kinetics. These mutations define a novel pheno- type within type I collagen defects. In combination with a recently reported adult with proα1(I)Ala1040Thr substitution (Int Conn Tis 82S1: CC01), our cases suggest that defects in proα1(I) processing lead to high BMD in childhood, with signs of osteopetrosis occurring subsequently. Pro-α1(I) cleavage appears crucial to C-propeptide processing, while defective pro-α2(I) specific or non-specific clea- vage occurs after α1(I) processing. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.152 P241 Association of common aromatase gene polymorphisms and bone mineral density: Epidemiological and functional evidence J.A. Riancho a, *, C. Sañudo a , C. Valero a , C. Pipaon b , J.M. Olmos a , V. Mijares a , J.L. Fernandez-Luna b , M.D. Perez-Aguilar c , J.R. Prieto c , M.T. Zarrabeitia d a Internal Medicine, Hospital U.M.Valdecilla, Univ. Cantabria, Santander, Spain b Molecular Genetics, Hospital U.M.Valdecilla, Univ. Cantabria, Santander, Spain c Orthopedics and Traumatology, Hospital U.M.Valdecilla, Univ. Cantabria, Santander, Spain d Legal Medicine, Hospital U.M.Valdecilla, Univ. Cantabria, Santander, Spain Estrogen activity in postmenopausal women depends on the aromatization of androgenic precursors in non-gonadal tissues. Therefore, aromatase is an appealing candidate gene to explain, in part, the genetic component of BMD. In fact, an association between Abstracts / Bone 44 (2009) S339–S450 S344