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Intact parathyroid hormone (PTH) in serum was determined in a random population sample and was related to age, sex, body composition, life-style factors, blood pressure, blood lipids, plasma fibrinogen, and serum IGF-1, osteocalcin, and vitamin D. Within the framework of the WHO MONICA Project in the city of Göteborg, Sweden, 181 men and 166 women aged 25-64 years were studied. Intact PTH concentrations varied with age but were similar in both sexes (range 4-82 ng/liter) [mean (+/- SD) 23.8 +/- 10.4 ng/liter in men and 25.1 +/- 10.6 ng/liter in women]. Intact PTH concentrations increased with increasing age, body mass index, systolic blood pressure, and 1,25(OH)2D3 and decreased with increasing 25(OH)D3 in all subjects. Additionally, in men, intact PTH correlated positively to diastolic blood pressure and negatively to coffee consumption. In women, PTH also correlated negatively to smoking and IGF-1. In a multivariate analysis including all variables, age lost its significance. In both sexes there were independent positive relations between intact PTH and body mass index and 1,25(OH)2D3, and negative relations between PTH and smoking habits as well as 25(OH)D3; among men there was also negative relations between PTH and coffee consumption. The results indicate that life-style factors such as smoking and coffee consumption decrease the serum concentration of intact PTH, and the same effect is seen in individuals with low body mass index. Coffee intake, smoking, and low body mass index are also known to adversely affect bone mineral content, highlighting the relationship between PTH and bone metabolism.

Disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC) is defined by familial adult-onset behavioral disturbance, followed by frontal lobe dementia, parkinsonism, and amyotrophy in variable proportions. A genetic etiology of DDPAC was suspected because of the familial clustering in family Mo, despite their wide geographic distribution. We have mapped the DDPAC locus to a 12-cM (sex averaged) region between D17S800 and D17S787 on chromosome 17q21-22. The basis for the variability of the clinical findings and pathology in DDPAC is unknown but suggests that the DDPAC locus should be screened as a candidate locus in family studies of conditions with behavioral abnormalities and neurological degeneration.

The DYT1 gene on chromosome 9q34 underlies idiopathic torsion dystonia (ITD) in Jewish and non-Jewish families with childhood and adolescent-onset dystonia that usually starts in a limb, spreads to other limbs, and uncommonly involves cranial muscles. We examined 39 members of a Mennonite family of German ancestry in which seven were affected with ITD. Age at onset was 14.7 years (range 5-34 years) and symptoms began in a limb in four. The remaining three had onset in the neck, face, and larynx. Dystonia progressed to involve at least one arm and one leg in all seven and there was cranial involvement in six. Five of these six had moderate or severe speech impairment. Linkage analysis with 9q34 markers excluded the region containing the DYT1 locus in this family. This study suggests that a gene other than DYT1 underlies some cases of early limb-onset ITD. The clinical features of prominent cranial involvement and impaired speech distinguish this "non-DYT1" early-onset ITD family from the typical DYT1 phenotype.

Objective: There is a clinical need for population based reference values for serum insulin-like growth factor I (IGF-I). We have therefore determined serum IGF-I concentrations in a random population sample from Sweden and have related the levels to age, sex, life style factors, blood pressure, body composition, blood lipids, plasma fibrinogen, parathyroid hormone (PTH) and osteocalcin., Patients: Within the framework of the WHO MONICA Project in the city of Göteborg, Sweden, 197 men and 195 women aged 25-64 years were studied., Results: Women aged 25-34 years had higher IGF-I concentration than men (mean 278 vs 227 micrograms/l) but in the interval 55-64 years values were lower in women than in men (158 vs 171 micrograms/l). IGF-I correlated positively with height and inversely with age, body mass index, systolic blood pressure and total cholesterol in both sexes. Negative relations between IGF-I and high density lipoprotein-cholesterol, as well as with amount of tobacco smoked, were found in men, and between IGF-I and diastolic blood pressure, triglycerides and PTH in women. When age was allowed for in multivariate analyses, most of these relations disappeared. However, among men IGF-I was positively associated with fibrinogen and negatively with age and smoking. IGF-I was negatively associated with age and coffee consumption in women., Conclusion: The present data can be used as reference values for IGF-I (at least in Caucasians) for the diagnosis of growth hormone disturbances and as guidelines for growth hormone substitution.

Objective: To investigate the possibility that neuroepithelial tumors in Turcot's syndrome are caused by pleiotropic mutations in the gene for adenomatous polyposis coli (APC), a tumor-suppressor gene implicated in colonic cancer., Methods: We studied the inheritance patterns of genetic markers for the chromosome 5q21 region in 12 members of a Turcot's syndrome kindred with five affected members. We performed linkage analysis to detect linkage between the disease phenotype and DNA markers., Results: Marker D5S346, located 30 to 70 kilobases from the APC locus, showed evidence highly suggestive of linkage to the disease phenotype (lod score = 1.92)., Conclusions: The data provide evidence that the tumor-suppressor gene implicated in APC and sporadic colon cancers may also cause malignant neuroepithelial tumors in Turcot's syndrome.

Dopa-responsive dystonia (DRD) is an autosomal-dominant neurological disorder which appears to result from a genetically determined deficiency of striatal dopamine. Pathological evidence suggests that this may be due to the establishment of a reduced number of dopaminergic nerve terminals in the striatum, or to an excessive reduction (pruning) of these terminals in early development. We have mapped the DRD gene to chromosome 14 by linkage analysis in 3 families with a maximum 2-point lod score of 4.67 at 8.6 centiMorgans from D14S63; maximum multipoint lod scores > 6 were obtained for the intervals D14S47-D14S52 and D14S52-D14S63. The flanking loci D14S47 and D14S63 define a region of about 22 cM as containing the DRD gene.

"Lubag" is an X-linked disorder causing dystonia and parkinsonism that has only been described in families from the Philippines, principally from the island of Panay. We have established linkage between the disease phenotype "lubag" and DNA markers which span the Xp11.22-Xq21.3 region by using a large Filipino family with 8 affected men in three generations. These DNA markers define an interval of about 20 centimorgans in the pericentromeric region of the X chromosome as the most likely site of the disease locus XDPD (X-linked dystonia-parkinsonism). XDPD has a maximum multipoint log likelihood ratio score (Zmax) of about 4.6 over the interval from Xq12 to Xq21.31 (DXS159-DXYS1X). The co-occurrence of dystonia and parkinsonism in lubag and in other known disorders suggests there may be a common pathogenetic mechanism. Identification of the genetic defect in this family may provide an important clue toward understanding the pathogenesis and pathophysiology of both dystonia and parkinsonism.

The process of transduction of a proto-oncogene involves the loss of intervening sequences, the loss of 3' mRNA terminal sequences, and possible base changes. It is not possible to know how similar the c-rel sequences we studied are to sequences from which v-rel arose. If one of the alleles we studied is identical to progenitor sequences of v-rel, then base changes must have occurred during the process of transduction. Alternatively, there may exist an allele of c-rel which did not need to undergo base changes to give rise to v-rel. The polymorphism of c-rel within a turkey population and between chicken and turkey shows clear evidence in c-rel coding sequences have not been detected within a turkey population. There is an EcoRI site in c-rel from turkey which is not in v-rel. There are unequal length substitutions in c-rel within the turkey population and between chicken and turkey. Unequal length substitutions can be explained if there has been a combination of two events, for example, insertion or deletion with extensive base changes, or two insertions or deletions. Two events occurring in a short evolutionary time span might occur if c-rel is diverging at a relatively fast rate. c-rel is much less conserved across species lines, in nucleic acid hybridization to v-rel (Chen et al. 1981; Wong and Lai 1981) than other proto-oncogenes, consistent with it diverging at a relatively fast rate. Since the evolutionary changes that have been seen for c-rel are in noncoding sequences, it is most likely that v-rel arose by transduction of a somatic mutation generated variant of c-rel or by transduction which involves sequence changes or later mutations.