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1.
A genetic linkage study between benign hereditary chorea and the locus D4S10 using the DNA probe G8 has shown two recombinations in five small families. There were negative lod scores at recombination fractions that show conclusive evidence of linkage in 16 larger British Huntington's disease families. We suggest that although benign hereditary chorea and Huntington's disease may have some clinical similarities they are probably at two different loci. 相似文献
2.
Linkage of a medium sized Scottish autosomal dominant retinitis pigmentosa family to chromosome 7q. 总被引:3,自引:0,他引:3
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Z Mohamed C Bell H M Hammer C A Converse L Esakowitz N E Haites 《Journal of medical genetics》1996,33(8):714-715
Retinitis pigmentosa is a group of hereditary retinopathies which is both clinically and genetically heterogeneous. Autosomal dominant (ADRP), autosomal recessive (ARRP), and X linked recessive (XLRP), as well as digenic forms of inheritance have been reported. ADRP has been linked to 3q, 6p, 7p, 7q, 8cen, 17p, 17q, and 19q. Three unrelated ADRP families have been reported to show linkage to 7q. We tested a Scottish ADRP family with microsatellite markers mapping within the 7q31-q35 region, and found three markers (D7S487, D7S514, D7S530) showing statistically significant evidence of linkage. A maximum two point lod score of 3.311 at 0% recombination was obtained for D7S514. 相似文献
3.
M Bayés B Goldaracena A Martínez-Mir M I Iragui-Madoz T Solans P Chivelet E Bussaglia M A Ramos-Arroyo M Baiget L Vilageliu S Balcells R Gonzàlez-Duarte D Grinberg 《Journal of medical genetics》1998,35(2):141-145
Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous disease. To date, mutations in four members of the phototransduction cascade have been implicated in ARRP. Additionally, linkage of the disease to three loci on 1p, 1q, and 6p has been described. However, the majority of cases are still uncharacterised. We have performed linkage analysis in a large nuclear ARRP family with five affected sibs. After exclusion of several regions of the genome known to contain loci for retinal dystrophies, a genomic search for linkage to ARRP was undertaken. Positive lod scores were obtained with markers on 2q31-q33 (Zmax at theta = 0.00 of 4.03, 4.12, and 4.12 at D2S364, D2S118, and D2S389, respectively) defining an interval of about 7 cM for this new ARRP locus, between D2S148 and D2S161. Forty-four out of 47 additional ARRP families, tested with markers on 2q32, failed to show linkage, providing evidence of further genetic heterogeneity. 相似文献
4.
Patel H Hart PE Warner T Allen I Phillimore HE Silver JR Wood NW Jeffery S Patton MA Crosby AH 《American journal of medical genetics》2001,102(1):68-72
The hereditary spastic paraplegias are a clinically variable and genetically heterogeneous group of disorders characterized by progressive and lower limb spasticity and weakness. Silver syndrome (SS) is a particularly disabling autosomal dominant form of the disease in which there is associated wasting of the hand muscles. In view of the fact that genes for hereditary spastic paraplegia can produce highly variable phenotypes, the eight known autosomal dominant loci were investigated for linkage to Silver syndrome. Genotyping of these loci in two large multigenerational families was incompatible with linkage to any of these regions, suggesting that an additional locus is responsible for this syndrome. 相似文献
5.
Distal hereditary motor neuropathy type II (distal HMN II): mapping of a locus to chromosome 12q24 总被引:3,自引:0,他引:3
Timmerman V; De Jonghe P; Simokovic S; Lofgren A; Beuten J; Nelis E; Ceuterick C; Martin JJ; Van Broeckhoven C 《Human molecular genetics》1996,5(7):1065-1069
The distal hereditary motor neuropathy (distal HMN) or the spinal form of
Charcot-Marie-Tooth (CMT) disease is an exclusively motor disorder of the
peripheral nervous system. The disorder clinically resembles the hereditary
motor and sensory neuropathies (HMSN) type I and type II or CMT type 1 and
type 2. Distal HMN might also be related to the spinal muscular atrophies
(SMA) since, in both disorders, the lower motor neurons are affected.
Electrophysiological and neuropathological examinations of peripheral
nerves show the absence of sensory involvement. We performed a genome
search in an extended Belgian family with autosomal dominant distal HMN
type II. Significant linkage was obtained with markers located at
chromosome 12q24, and the gene for distal HMN II was assigned to the 13 cM
interval between D12S86 and D12S340.
相似文献
6.
C Espinós C Nájera J M Millán C Ayuso M Baiget H Pérez-Garrigues O Rodrigo C Vilela M Beneyto 《Journal of medical genetics》1998,35(5):391-398
Usher syndrome (USH) is an autosomal recessive hereditary disorder characterised by congenital sensorineural hearing loss and gradual visual impairment secondary to retinitis pigmentosa (RP). The disorder is clinically and genetically heterogeneous. With regard to Usher type I (USH1), several subtypes have been described, the most frequent being USH1B located on chromosome 11q13.5. Of 18 USH1 families studied by linkage analysis, 12 (67%) showed significant lod score values for locus D11S527 (Zmax=14.032, theta=0.000) situated on chromosome 11q. Our findings suggest considerable genetic heterogeneity in the Spanish USH1 population. It is important to note that one of our families linked to the USH1B locus shows interesting intrafamilial clinical variability. As regards the remaining six USH1 families, the linkage analysis did not provide conclusive data, although two of them show slight linkage to markers located on chromosome 3q (Zmax=1.880, theta=0.000 for D3S1279), the same location that had previously been assigned to some USH3 families. 相似文献
7.
Wierzbicki AS Mitchell J Lambert-Hammill M Hancock M Greenwood J Sidey MC de Belleroche J Gibberd FB 《European journal of human genetics : EJHG》2000,8(8):649-651
Refsum's disease (MIM 266500) is a recessive disorder characterised by defective peroxisomal alpha-oxidation of phytanic acid. A Refsum's disease gene, phytanoyl-CoA hydroxylase (PAHX), has been localised to chromosome 10p13 between the markers D10S226-D10S223. This study investigated whether all cases of Refsum's disease were linked with chromosome 10p13. Eight genetically informative families comprising 92 individuals including 17 living patients with a Refsum's disease phenotype and initial plasma phytanic acid > 200 micromol/L were recruited. Linkage to the 10pter-10p11.2 region was investigated using a panel of eight dinucleotide repeat markers. Linkage analysis of this phenotypically identical cohort suggested that Refsum's disease was genetically heterogeneous (Zmax = 5.28, alpha = 0.45). Two subgroups were identified. One group of four families with eight affected individuals had a maximum multipoint lod score for linkage of 3.89 in the region D10S547 to D10S191, whilst in another three families with nine affected individuals linkage to this region was definitely excluded. Our results show that Refsum's disease is genetically heterogeneous, with up to 55% of cases not being linked to the PAHX gene locus at D10S547 to D10S223. This suggests that Refsum's disease, in common with other peroxisomal 'diseases', may be more accurately described as a heterogeneous syndrome. 相似文献
8.
Muglia M Magariello A Citrigno L Passamonti L Sprovieri T Conforti FL Mazzei R Patitucci A Gabriele AL Ungaro C Bellesi M Quattrone A 《Clinical genetics》2008,73(5):486-491
The distal hereditary motor neuropathy (dHMN) is a rare genetically and clinically heterogeneous disorder characterized by weakness and wasting of distal limb muscles in absence of overt sensory abnormalities. Recently, pyramidal signs have been also described in some patients with dominant or recessive dHMN, and two different loci have been identified in families affected by dHMN complicated with pyramidal dysfunction. We investigated an Italian family affected by an autosomal dominant dHMN complicated by pyramidal signs in order to map a new gene locus. The disease maps to a novel locus in a 26-cM region flanked by D4S1552 and D4S2930 on chromosome 4q34.3-35.2. Three candidate genes ( SNX25 , CASP3 and TUBB4Q ) located in the critical region were screened for the presence of mutations by heteroduplex analysis. No mutations have been detected in the analyzed genes. In conclusion, the new private genetic locus we reported further confirms the wide heterogeneity of dHMN. 相似文献
9.
Genetic heterogeneity in Korean families with autosomal-dominant polycystic kidney disease (ADPKD): the first Asian report 总被引:4,自引:0,他引:4
Lee JG Lee KB Kim UK Ahn C Hwang DY Hwang YH Eo HS Lee EJ Kim YS Han JS Kim S Lee JS 《Clinical genetics》2001,60(2):138-144
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease in adults, and the prevalence of this disease within the chronic haemodialysis patient population is known to be approximately 2% in Korea. So far, three genetic locus have been identified as being responsible for ADPKD, and approximately 85% of the cases in Western countries are related to the PKD1 gene. However, little information is available concerning the pattern of linkage analysis in Asian populations. METHODS: 48 families with hereditary renal cysts were recruited by consent and their molecular genetic characteristics were studied. Linkage analysis was done with microsatellite markers (PKD1: SM7, UT581, AC2.5, KG8, D16S418; PKD2: D4S423, D4S1534, D4S1542, D4S1544, D4S2460). Genomic DNA polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) gel run were performed, and the resultant allele patterns were compared with sonographic findings. RESULTS: The results of this study showed that the ratio PKD1:PKD2 was 31:8, and that the PKD2 families exhibited a tendency toward a milder renal prognosis than the PKD1 families. CONCLUSION: We confirmed the applicability of linkage analysis for ADPKD in the Korean population, and our data confirmed a similar incidence of PKD1 (79%) and PKD2 (21%) in Korean patients as in the Western population. 相似文献
10.
Exclusion mapping of the hereditary dentatorubropallidoluysian atrophy gene from the Huntington''s disease locus. 总被引:1,自引:0,他引:1
I Kondo H Ohta M Yazaki J E Ikeda J F Gusella I Kanazawa 《Journal of medical genetics》1990,27(2):105-108
Hereditary dentatorubropallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder. Clinical and genetic findings in hereditary DRPLA are very similar to those of Huntington's disease (HD). However, it can be differentiated from HD by the pathological findings of dentatorubral and pallidoluysian atrophies and by a lack of prominent atrophy of the striatum at necropsy. The hereditary DRPLA gene has not been localised and the possibility that the two disease loci are allelic has been suggested. We have searched for linkage between the locus for hereditary DRPLA and D4S10 using the G8 probe, which is a genetic marker linked to HD. In four families, there were negative scores at all recombination fractions and the lod score was -2.215 at recombination fraction theta = 0.15. These data indicate that the locus for hereditary DRPLA is not closely linked to D4S10 and that hereditary DRPLA is a distinct disease from HD. 相似文献
11.
Bayrak-Toydemir P McDonald J Akarsu N Toydemir RM Calderon F Tuncali T Tang W Miller F Mao R 《American journal of medical genetics. Part A》2006,140(20):2155-2162
Hereditary hemorrhagic telangiectasia (HHT) is a genetically and clinically heterogeneous multisystem vascular dysplasia. Mutations of the endoglin and ACVRL1 genes are known to cause HHT. However, existence of HHT families in which linkage to these genes has been excluded has suggested that other gene(s) can cause HHT in some families. Recently, a family was reported to be linked to chromosome 5q, the HHT3 locus. Here we report on linkage results on a family with classic features of HHT, albeit a less severe phenotype with regards to epistaxis and telangiectases, in which linkage to HHT1, HHT2, and HHT3 is ruled out. Whole genome linkage analysis and fine mapping results suggested a 7 Mb region on the short arm of chromosome 7 (7p14) between STR markers D7S2252 and D7S510. We obtained a maximum two point LOD score of 3.60 with the STR marker D7S817. This region was further confirmed by haplotype analysis. These findings suggest the presence of another gene causing HHT (HHT4). The features in this family that strongly suggest the presence of a hereditary, multisystem vascular dysplasia would be easily missed during the typical evaluation and management of a patient with an AVM. This family helps emphasize the need to obtain a very detailed, targeted medical and family history for even mild, infrequent but recurring nosebleed, subtle telangiectases. Further studies of the candidate region and the identification of the gene responsible for the vascular anomalies in this family will add to our understanding of vascular morphogenesis and related disorders. 相似文献
12.
Charcot-Marie-Tooth disease type 1a (CMT1a): evidence for trisomy of the region p11.2 of chromosome 17 in south Wales families.
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The gene for Charcot-Marie-Tooth disease type 1a (CMT1a) has been localised to chromosome 17p11.2. Locus D17S122 is recognised by the DNA probe pVAW409R3 which detects an MspI polymorphism with three alleles in the normal population. Subjects with CMT1a show evidence of trisomy for this region of chromosome 17 by displaying either all three alleles or a dosage effect when only two alleles are present. This phenomenon was seen in 10 out of 11 families with type I hereditary motor and sensory neuropathy (HMSN) where affected subjects were heterozygous for the MspI polymorphisms. This mutation is likely to have arisen from a non-reciprocal recombination event between non-sister chromatids of homologous chromosomes at meiosis I. The detection of this partial trisomy offers a rapid method for the diagnosis of CMT1a in families not suitable for linkage analysis. 相似文献
13.
Klebe S Lossos A Azzedine H Mundwiller E Sheffer R Gaussen M Marelli C Nawara M Carpentier W Meyer V Rastetter A Martin E Bouteiller D Orlando L Gyapay G El-Hachimi KH Zimmerman B Gamliel M Misk A Lerer I Brice A Durr A Stevanin G 《European journal of human genetics : EJHG》2012,20(6):645-649
The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterised by progressive spasticity in the lower limbs. The nosology of autosomal recessive forms is complex as most mapped loci have been identified in only one or a few families and account for only a small percentage of patients. We used next-generation sequencing focused on the SPG30 chromosomal region on chromosome 2q37.3 in two patients from the original linked family. In addition, wide genome scan and candidate gene analysis were performed in a second family of Palestinian origin. We identified a single homozygous mutation, p.R350G, that was found to cosegregate with the disease in the SPG30 kindred and was absent in 970 control chromosomes while affecting a strongly conserved amino acid at the end of the motor domain of KIF1A. Homozygosity and linkage mapping followed by mutation screening of KIF1A allowed us to identify a second mutation, p.A255V, in the second family. Comparison of the clinical features with the nature of the mutations of all reported KIF1A families, including those reported recently with hereditary sensory and autonomic neuropathy, suggests phenotype-genotype correlations that may help to understand the mechanisms involved in motor neuron degeneration. We have shown that mutations in the KIF1A gene are responsible for SPG30 in two autosomal recessive HSP families. In published families, the nature of the KIF1A mutations seems to be of good predictor of the underlying phenotype and vice versa. 相似文献
14.
15.
Iannuzzi MC Iyengar SK Gray-McGuire C Elston RC Baughman RP Donohue JF Hirst K Judson MA Kavuru MS Maliarik MJ Moller DR Newman LS Rabin DL Rose CS Rossman MD Teirstein AS Rybicki BA 《Genes and immunity》2005,6(6):509-518
Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the US, African Americans are more commonly affected with sarcoidosis and suffer greater morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by conducting a genome-wide, sib pair multipoint linkage analysis in 229 African-American families ascertained through two or more sibs with a history of sarcoidosis. Using the Haseman-Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome 5q11 (P=0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans. Fine mapping of the linked regions, particularly on chromosome 5q, should help to refine linkage signals and guide further sarcoidosis candidate gene investigation. 相似文献
16.
Stephan Klebe Alexandra Durr Naima Bouslam Djamel Grid Caroline Paternotte Christel Depienne Sylvain Hanein Ahmed Bouhouche Nizar Elleuch Hamid Azzedine Sandrine Poea-Guyon Sylvie Forlani Elodie Denis Céline Charon Jamile Hazan Alexis Brice Giovanni Stevanin 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2007,(7):854-861
Thirty-three different loci for hereditary spastic paraplegias (HSP) have been mapped, and 15 responsible genes have been identified. Autosomal recessive spastic paraplegias (ARHSPs) usually have clinically complex phenotypes but the SPG5, SPG24, and SPG28 loci are considered to be associated with pure forms of the disease. We performed a genome-wide scan in a large French family. Fine mapping of the refined SPG5 region on chromosome 8q12 was performed in another 17 ARHSP families with additional microsatellite markers. After exclusion of known ARHSP loci, the genome-wide screen provided evidence of linkage with a maximal multipoint lod score of 2.6 in the D8S1113-D8S1699 interval. This interval partially overlapped SPG5 and reduced it to a 5.9 megabase (Mb)-region between D8S1113 and D8S544. In a family of Algerian origin from a series of 17 other ARHSP kindreds, linkage to the SPG5 locus was supported by a multipoint lod score of 2.3. The direct sequencing of the coding exons of seven candidate genes did not detect mutations/polymorphisms in the index cases of both linked families. The phenotype of the two SPG5-linked families consisted of spastic paraparesis associated with deep sensory loss. In several patients with long disease durations, there were also mild cerebellar signs. The frequency of SPG5 was approximately 10% (2/18) in our series of ARHSP families with pure or complex forms. We have refined the SPG5 locus to a 3.8 cM interval and extended the phenotype of this form of ARHSP to include slight cerebellar signs. 相似文献
17.
Bolino A; Brancolini V; Bono F; Bruni A; Gambardella A; Romeo G; Quattrone A; Devoto M 《Human molecular genetics》1996,5(7):1051-1054
Hereditary motor and sensory neuropathy (HMSN) with focally folded myelin
sheaths, or Charcot-Marie-Tooth type 4B (CMT4B), is a distinct clinical
entity belonging to the heterogeneous group of autosomal recessive
demyelinating neuropathies. We first described a large pedigree with CMT4B,
which showed a high consanguinity level and an autosomal recessive pattern
of inheritance. Through conventional linkage analysis, we excluded linkage
of the locus segregating in this pedigree to any of the known genes
responsible for other HMSNs. Using homozygosity mapping and haplotype
sharing analysis, we were able to localize the disease gene in a 4 cM
interval on chromosome 11q23, between the D11S1332 and D11S917 loci. On the
basis of the clinical characteristics of the disease, we propose that this
locus corresponds to the CMT4B gene.
相似文献
18.
Andrea Novelletto Paola Mandich Emilia Bellone Patrizia Malaspina Giuseppa Vivona Franco Ajmar Marina Frontali 《American journal of medical genetics. Part A》1991,40(3):374-376
A group of Huntington disease (HD) families of Italian ancestry was analyzed for 11 RFLPs from genetic loci mapped in 4p16 and genetically linked to the HD gene. We found a statistically significant difference of allele distributions in HD vs normal chromosomes for loci D4S10, D4S127, and D4S43. This observation increases the number of loci in linkage disequilibrium with HD. However, the amount of disequilibrium does not allow either a finer localization of the HD gene or a substantial improvement in risk calculations. 相似文献
19.
A Novelletto P Mandich E Bellone P Malaspina G Vivona F Ajmar M Frontali 《American journal of medical genetics》1991,40(3):374-376
A group of Huntington disease (HD) families of Italian ancestry was analyzed for 11 RFLPs from genetic loci mapped in 4p16 and genetically linked to the HD gene. We found a statistically significant difference of allele distributions in HD vs normal chromosomes for loci D4S10, D4S127, and D4S43. This observation increases the number of loci in linkage disequilibrium with HD. However, the amount of disequilibrium does not allow either a finer localization of the HD gene or a substantial improvement in risk calculations. 相似文献
20.
F. Ajmar P. Mandich E. Bellone G. Abbruzzese 《American journal of medical genetics. Part A》1991,39(2):211-214
Twelve Italian families with Huntington disease were tested with 10 probes known to be linked to the disease locus and able to detect polymorphisms at the following loci on chromosome 4: D4S10, D4S127, D4S95, D4S43, D4S115, D4S111, D4S90. The results confirmed the applicability of the linkage approach for presymptomatic diagnosis in Italian families. Positive lod scores were found between D4S10, D4S95, D4S43 and the disease, wherease D4S90 did not indicate significant linkage values. With the limitations due to the small size of the tested sample, no genetic heterogeneity was detected in the families examined for loci D4S10, D4S95/S127, D4S43. 相似文献