Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The autosomal recessive disorder Bardet-Biedl syndrome is characterised by retinal degeneration, polydactyly, obesity, mental retardation, hypogenitalism, renal dysplasia, and short stature. It is heterogeneous with at least four gene loci (BBS1-4) having been mapped to date. We have studied 18 multiply affected families noting the presence of both major and minor manifestations. Using a fluorescently based PCR technique, we genotyped each family member and assigned linkage to one of the four loci. Given this degree of heterogeneity we hoped to find phenotypic differences between linkage categories. We found 44% of families linked to 11q13 (BBS1) and 17% linked to 16q21 (BBS2). Only one family was linked to 15q22 (BBS4) and none to 3p12. We conclude that BBS1 is the major locus among white Bardet-Biedl patients and that BBS3 is extremely rare. Only subtle phenotypic differences were observed, the most striking of which was a finding of taller affected offspring compared with their parents in the BBS1 category. Affected subjects in the BBS2 and 4 groups were significantly shorter than their parents. Twenty eight percent of pedigrees did not show linkage to any known locus, evidence for at least a fifth gene. We conclude that the different genes responsible for Bardet-Biedl syndrome may influence growth characteristics such as height.
 ...
PMID:Bardet-Biedl syndrome: a molecular and phenotypic study of 18 families. 903 82

Bardet-Biedl syndrome (BBS) is a clinically and genetically heterogeneous autosomal recessive disorder characterized by retinitis pigmentosa, polydactyly, obesity, hypogenitalism, mental retardation, and renal anomalies. To detect linkage to BBS loci, 29 BBS families, of mixed but predominantly European ethnic origin, were typed with 37 microsatellite markers on chromosomes 2, 3, 11, 15, 16, and 17. The results show that an estimated 36-56% of the families are linked to the 11q13 chromosomal site (BBS1) previously described by M. Leppert et al. (1994, Nature Genet. 7, 108-112), with the gene order cen-D11S480-5 cM-BBS1-3 cM-D11S913/D11S987-qter. A further 32-35% of the families are linked to the BBS4 locus, reported by R. Carmi et al. (1995, Hum. Mol. Genet. 4, 9-13) in chromosomal region 15q22.3-q23, with the gene order cen-D15S125-5 cM-BBS4-2 cM-D15S131/D15S204-qter. Three consanguineous BBS families are homozygous for three adjacent chromosome 15 markers, consistent with identity by descent for this region. In one of these families haplotype analysis supports a localization for BBS4 between D15S131 and D15S114, a distance of about 2 cM. Weak evidence of linkage to the 16q21 (BBS2) region reported by A. E. Kwitek-Black et al. (1993, Nature Genet. 5, 392-396) was observed in 24-27% of families with the gene order cen-D16S408-2 cM-BBS2-5 cM-D16S400. A fourth group of families, estimated at 8%, are unlinked to all three of the above loci, showing that at least one other BBS locus remains to be found. No evidence of linkage was found to markers on chromosome 3, corresponding to the BBS3 locus, reported by V. C. Sheffield et al. (1994, Hum. Mol. Genet. 3, 1331-1335), or on chromosome 2 or 17, arguing against the involvement of a BBS locus in a patient with a t(2;17) translocation.
 ...
PMID:Linkage mapping in 29 Bardet-Biedl syndrome families confirms loci in chromosomal regions 11q13, 15q22.3-q23, and 16q21. 912 87

There are at least five distinct Bardet-Biedl syndrome (BBS) loci, four of which have been mapped: 11q (BBS1), 16q (BBS2), 3p (BBS3), and 15q (BBS4). A comparative study of the three Arab-Bedouin kindreds used to map the BBS2, BBS3, and BBS4 loci suggests that the variability in the number and severity of clinical manifestations, particularly the pattern of polydactyly, reflects chromosome-specific subtypes of BBS [Carmi et al., 1995a; Am J Med Genet 59:199-203]. We describe a Newfoundland kindred of northern European descent and confirm the initial finding of a BBS locus on chromosome 3. However, the "BBS3 phenotype," which includes polydactyly of all four limbs and a progression to morbid obesity, was not observed. Rather, four of the five BBS patients in this family had polydactyly restricted to their feet. The obesity in these patients was reversible with caloric restriction and/or exercise. Mental retardation has been considered a major symptom of BBS. However, formal IQ testing shows that these patients are of average intelligence. Haplotype analysis reduces the BBS3 critical region to a 6-cM interval between D3S1595-D3S1753.
 ...
PMID:Canadian Bardet-Biedl syndrome family reduces the critical region of BBS3 (3p) and presents with a variable phenotype. 971 14

Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive disease characterized by retinal dystrophy, renal structural abnormalities, obesity, dysmorphic extremities, and hypogenitalism in males. BBS is genetically heterogeneous with four known loci: BBS1 (11q), BBS2 (16q), BBS3 (3p), and BBS4 (15q). The prevalence of BBS in Newfoundland is approximately 10-fold greater than in Switzerland (1:160,000) and similar to the prevalence among the Bedouin of Kuwait (1:13,500). A population-based genetic survey was performed on 17 BBS families from the island portion of the province of Newfoundland, a comparatively isolated region of Canada. The families in the study had a total of 36 well-documented, affected individuals with 12 families having 2 or more affected individuals. Linkage at each of the four known loci was tested with two-point linkage and haplotype analysis. Three of the 17 kindreds showed linkage to 11q, 1 to 16q, and 1 to 3p. The latter is the first BBS3 family identified in a population of northern European descent. Six families remain undetermined because of poor pedigree structure or inconclusive haplotype analyses. Six families were excluded from all four known BBS loci, indicating that there is at least a fifth BBS locus (BBS5).
 ...
PMID:Genetic heterogeneity of Bardet-Biedl syndrome in a distinct Canadian population: evidence for a fifth locus. 988 93

Bardet-Biedl Syndrome (BBS) is a heterogeneous, autosomal recessive disorder characterized by mental retardation, obesity, retinitis pigmentosa, syndactyly and/or polydactyly, short stature, and hypogenitalism and is caused by mutations at a number of distinct loci. Using a positional cloning approach for identifying the BBS4 (chromosome 15) gene, we identified and cloned an unconventional myosin gene, myosin IXA (HGMW-approved symbol MYO9A). Since mutations in unconventional myosins are known to cause several human diseases, and since mutations of unconventional myosin VIIa cause retinal degeneration, we evaluated myosin IXA as a candidate for BBS. We exploited PCR-based techniques to clone a 8473-nt cDNA for myosin IXA. A 7644-bp open reading frame predicts a protein with all the hallmarks of class IX unconventional myosins. Human Northern blot analysis and in situ hybridization of mouse embryos reveal that myosin IXA is expressed in many tissues consistent with BBS. Intron/exon boundaries were identified, and myosin IXA DNA and RNA from BBS4 patients were evaluated for mutation.
 ...
PMID:The cloning and developmental expression of unconventional myosin IXA (MYO9A) a gene in the Bardet-Biedl syndrome (BBS4) region at chromosome 15q22-q23. 1040 26

Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive disorder; major phenotypic findings include dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal anomalies. In the majority of northern European families with BBS, the syndrome is linked to a 26-cM region on chromosome 11q13. However, the finding, so far, of five distinct BBS loci (BBS1, 1q; BBS2, 16q; BBS3, 3p; BBS4, 15q; BBS5, 2q) has hampered the positional cloning of these genes. We use linkage disequilibrium (LD) mapping in an isolated founder population in Newfoundland to significantly reduce the BBS1 critical region. Extensive haplotyping in several unrelated BBS families of English descent revealed that the affected members were homozygous for overlapping portions of a rare, disease-associated ancestral haplotype on chromosome 11q13. The LD data suggest that the BBS1 gene lies in a 1-Mb, sequence-ready region on chromosome 11q13, which should enable its identification.
 ...
PMID:A founder effect in the newfoundland population reduces the Bardet-Biedl syndrome I (BBS1) interval to 1 cM. 1057 22

Neuromedin B has been shown to exert an inhibiting effect on food consumption in rats. The corresponding gene NMB maps to chromosome 15q22.3-q23, a region expected to contain a gene for the Bardet-Biedl syndrome type 4 (BBS4). Based on its map position and the putative function of the encoded peptide, NMB can be considered as a candidate gene both for BBS4 and the development of human obesity. To examine its involvement in these phenotypes, we determined the genomic structure of human NMB, and performed a mutation screen in its coding region. In genomic DNA of six BBS4 patients and in a large population sample, two sequence variants were detected: a g.253C-->A transversion creating a P73T substitution and a g.401G-->A silent mutation changing the stop codon TGA into stop codon TAA. A case-control study with 92 extremely obese patients and 94 underweight students revealed a significant association between the g.401G-->A polymorphism and body weight (adjustedp = 0.03), which was confirmed in a validation sample consisting of 95 extremely obese patients, and 95 normal weight and 48 underweight individuals (Mann-Whitney p = 0.02). These results suggest a contribution of NMB or a gene in its close vicinity to genetic weight control in humans.
 ...
PMID:Significant association between a silent polymorphism in the neuromedin B gene and body weight in German children and adolescents. 1119 34

Three genes that encode related immunoglobulin superfamily molecules have recently been mapped to human chromosome 15 in the region q22.3-q23 and to the syntenic region on mouse chromosome 9. These genes presumably derived from gene duplications, and they are highly similar to Deleted in Colorectal Cancer (DCC), which functions as an axon guidance molecule during development of the nervous system. To find out whether additional genes of this class were present in a chromosomal cluster, we produced a comparative physical map within the region of synteny between mouse chromosome 9 and human chromosome 15. This interval overlaps the critical region for the fourth genetic locus for Bardet-Biedl syndrome (BBS4) in humans. Bardet-Biedl syndrome (OMIM 600374) is characterized by poly/syn/brachydactyly, retinal degeneration, hypogonadism, mental retardation, obesity, diabetes, and kidney abnormalities. A detailed map of this locus will help to identify candidate genes for this disorder.
 ...
PMID:09/15: Comparative genomics of a conserved chromosomal region associated with a complex human phenotype. 1131 7

Bardet-Biedl syndrome (BBS, MIM 209900) is a heterogeneous autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. The disorder is also associated with diabetes mellitus, hypertension, and congenital heart disease. Six distinct BBS loci map to 11q13 (BBS1), 16q21 (BBS2), 3p13-p12 (BBS3), 15q22.3-q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6). Although BBS is rare in the general population (<1/100,000), there is considerable interest in identifying the genes causing BBS because components of the phenotype, such as obesity and diabetes, are common. We and others have demonstrated that BBS6 is caused by mutations in the gene MKKS (refs. 12,13), mutation of which also causes McKusick-Kaufman syndrome (hydrometrocolpos, post-axial polydactyly, and congenital heart defects). MKKS has sequence homology to the alpha subunit of a prokaryotic chaperonin in the thermosome Thermoplasma acidophilum. We recently identified a novel gene that causes BBS2. The BBS2 protein has no significant similarity to other chaperonins or known proteins. Here we report the positional cloning and identification of mutations in BBS patients in a novel gene designated BBS4.
 ...
PMID:Identification of the gene that, when mutated, causes the human obesity syndrome BBS4. 1138 Dec 70

Bardet-Biedl syndrome (BBS) is an uncommon multisystemic disorder characterized primarily by retinal dystrophy, obesity, polydactyly, and renal dysfunction. BBS has been modeled historically as an autosomal recessive trait, under which premise six independent BBS loci (BBS1-BBS6) have been mapped in the human genome. However, extended mutational analyses of BBS2 and BBS6, the first two BBS genes cloned, suggest that BBS exhibits a more complex pattern of inheritance, in which three mutations at two loci simultaneously are necessary and sufficient in some families to manifest the phenotype. We evaluated the spectrum of mutations in the recently identified BBS4 gene with a combination of haplotype analysis and mutation screening on a multiethnic cohort of 177 families. Consistent with predictions from previous genetic analyses, our data suggest that mutations in BBS4 contribute to BBS in <3% of affected families. Furthermore, integrated mutational data from all three currently cloned BBS genes raise the possibility that BBS4 may participate in triallelic inheritance with BBS2 and BBS1, but not the other known loci. Establishment of the loci pairing in triallelism is likely to be important for the elucidation of the functional relationships among the different BBS proteins.
 ...
PMID:BBS4 is a minor contributor to Bardet-Biedl syndrome and may also participate in triallelic inheritance. 1201 87


1 2 3 4 Next >>