共查询到20条相似文献,搜索用时 62 毫秒
1.
Further refinement of Pendred syndrome locus by homozygosity analysis to a 0.8 cM interval flanked by D7S496 and D7S2425.
下载免费PDF全文
![点击此处可从《Journal of medical genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M Mustapha S T Azar Y B Moglabey M Saouda G Zeitoun J Loiselet R Slim 《Journal of medical genetics》1998,35(3):202-204
Pendred syndrome is an autosomal recessive disease characterised by congenital sensorineural deafness and goitre. The gene responsible for Pendred syndrome has been mapped to chromosome 7q31 in a 5.5 centimorgan (cM) interval flanked by D7S501 and D7S523. This interval was recently refined a to 1.7 cM interval located between D7S501 and D7S692. In the present study, we report linkage analysis data on a large consanguineous family genotyped with eight microsatellite markers located between D7S501 and D7S523. Complete cosegregation with the disease locus was observed with the loci analysed, which further supports locus homogeneity for Pendred syndrome and close linkage to this region. Haplotype analysis placed the Pendred syndrome gene between D7S496 and D7S2425 in a 0.8 cM interval. This additional refinement of the Pendred syndrome region will facilitate the construction of a physical map of the region and will help the identification of candidate genes. 相似文献
2.
John H. Greinwald Sigrid Wayne Achih H. Chen Daryl A. Scott Ross I.S. Zbar Michelle L. Kraft Sai Prasad Arabandi Ramesh Paul Coucke C.R. Srikumari Srisailapathy Michael Lovett Guy Van Camp Richard J.H. Smith 《American journal of medical genetics. Part A》1998,78(2):107-113
Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of hereditary hearing impairment (HHI). To date, 16 different loci have been reported, making ARNSHL an extremely heterogeneous disorder. One of these loci, DFNB4, was mapped to a 5-cM interval of 7q31 in a large Middle-Eastern Druze family. This interval also includes the gene for Pendred syndrome. We report on three new families with HHI from the Madras region of southern India that demonstrate linkage to 7q. Their pedigrees are compatible with autosomal recessive inheritance. Furthermore, the largest family identifies a novel locus (DFNB17) telomeric to the DFNB4 and Pendred intervals. A 3-cM region of homozygosity by descent between markers D7S486 and D7S2529 is present in all affected individuals in this family and generates a multipoint LOD score of 4.24. The two other families map to the previously reported DFNB4 region but have insufficient power to attain significant LOD scores. However, mutations in the Pendred syndrome gene are present in one of these families. Am. J. Med. Genet. 78:107–113, 1998. © 1998 Wiley-Liss, Inc. 相似文献
3.
Fluctuating sensorineural hearing loss associated with enlarged vestibular aqueduct maps to 7q31, the region containing the Pendred gene 总被引:17,自引:0,他引:17
Abe S Usami S Hoover DM Cohn E Shinkawa H Kimberling WJ 《American journal of medical genetics》1999,82(4):322-328
The most common form of inner ear abnormality, enlarged vestibular aqueduct (EVA), is of particular interest because it is associated with characteristic clinical findings, including fluctuating and sometimes progressive sensorineural hearing loss and disequilibrium symptoms. Although EVA has been reported to be inherited in a recessive manner, nothing else is known about the genetic basis of this hearing loss. Here we report on the localization of the gene responsible for sensorineural hearing loss associated with EVA to chromosomal region 7q31, with maximum multipoint LOD score of 3.647. The EVA candidate gene region lies in a 1.7-cM interval between the flanking markers D7S501 and D7S2425. Interestingly, this region overlaps the region containing the gene responsible for Pendred syndrome, called PDS, which was identified recently. However, the present subjects did not fulfill the criteria for Pendred syndrome. It is hypothesized that different mutations within the PDS gene may cause different phenotypes ranging from EVA to the Mondini deformity seen in Pendred syndrome. 相似文献
4.
Molecular analysis of the PDS gene in Pendred syndrome 总被引:18,自引:2,他引:18
Coyle B; Reardon W; Herbrick JA; Tsui LC; Gausden E; Lee J; Coffey R; Grueters A; Grossman A; Phelps PD; Luxon L; Kendall-Taylor P; Scherer SW; Trembath RC 《Human molecular genetics》1998,7(7):1105-1112
Pendred syndrome is an autosomal recessive disorder characterized by the
association between sensorineural hearing loss and thyroid swelling or
goitre and is likely to be the most common form of syndromic deafness.
Within the thyroid gland of affected individuals, iodide is incompletely
organified with variable effects upon thyroid hormone biosynthesis, whilst
the molecular basis of the hearing loss is unknown. The PDS gene has been
identified by positional cloning of chromosome 7q31, within the Pendred
syndrome critical linkage interval and encodes for a putative ion
transporter called pendrin. We have investigated a cohort of 56 kindreds,
all with features suggestive of a diagnosis of Pendred syndrome. Molecular
analysis of the PDS gene identified 47 of the 60 (78%) mutant alleles in 31
families (includes three homozygous consanguineous kindreds and one
extended family segregating three mutant alleles). Moreover, four recurrent
mutations accounted for 35 (74%) of PDS disease chromosomes detected and
haplotype analysis would favour common founders rather than mutational
hotspots within the PDS gene. Whilst these findings demonstrate molecular
heterogeneity for PDS mutations associated with Pendred syndrome, this
study would support the use of molecular analysis of the PDS gene in the
assessment of families with congenital hearing loss.
相似文献
5.
Cusano R Gangarossa S Forabosco P Caridi G Ghiggeri GM Russo G Iolascon A Ravazzolo R Seri M 《European journal of human genetics : EJHG》2000,8(11):895-899
Fechtner syndrome is an autosomal dominant disorder which has been thought to be a variant of Alport syndrome. It is characterised by nephritis, sensorineural hearing loss and eye abnormalities, as well as by macrothrombocytopenia and polymorphonuclear inclusion bodies. Recently, the Fechtner syndrome has been mapped in a 5.5 Mb region on the long arm of chromosome 22 by linkage analysis in an extended Israeli family. We describe here the genetic refinement of the Fechtner critical interval to a region less than 600 Kb by linkage analysis performed in a large Italian pedigree. The presence of several recombination events allowed the disease gene to be localised between markers D22S278 and D22S426, in a region containing only two non-recombinant markers, D22S1173 and D22S283. This interval, spanning <600 Kb on genomic DNA, has been entirely sequenced and contains six known and three putative genes. 相似文献
6.
The brittle hair syndrome (BHS) is characterized by short stature, intellectual impairment, brittle hair, and decreased fertility in 20 members from a large Amish consanguineous kindred previously reported affected with this syndrome. We mapped the BHS gene by genome scan to chromosome 7p14.1. Evidence of linkage was supported by a maximum multipoint LOD score of 6 obtained with GENEHUNTER for the linkage interval defined by markers D7S484-D7S2422 distant by 17.2 cM. Two-point linkage analysis performed with SUPERLINK yielded a LOD score of 9.02 at theta = 0 for marker D7S2497 located within that interval. Analysis of haplotypes homozygous-by-descent allowed fine mapping of the BHS gene within a 4.81 cM interval delimited by markers D7S2497 and D7S691, a region that spreads over 3.42 Mb. 相似文献
7.
Y. Wang K. Treat R. J. Schroer J. E. O'Brien R. E. Stevenson C. E. Schwartz 《American journal of medical genetics. Part A》1994,51(2):169-175
Branchio-oto-renal (BOR) syndrome is an autosomal dominant condition of branchial arch anomalies, deafness and renal dysplasia. Clinical manifestations tend to have considerable intrafamilial and interfamilial variability. Previous linkage studies had localized the gene responsible for BOR syndrome to a broad region of chromosome 8q. Using 10 microsatellite markers, we have further refined the localization of this disorder by establishing tight linkage to two markers, D8S279 and D8S530 (Zmax = 3.91 and Zmax = 2.83 respectively at Θ = 0.00. These markers are within 1 cM of one another. Multipoint analysis, involving 7 loci, placed the gene between these markers, with a lod-1 confidence interval 0.7 cM proximal to D8S530 and 0.6 cM distal to D8S279. © 1994 Wiley-Liss, Inc. 相似文献
8.
Delmaghani S Aghaie A Compain-Nouaille S Ataie A Lemainque A Zeinali S Lathrop M Weil D Petit C 《European journal of human genetics : EJHG》2003,11(10):816-818
We report on a novel localization for a recessive form of deafness (DFNB), by linkage analysis in an Iranian consanguineous family. Affected individuals suffer from prelingual profound sensorineural hearing loss. Genome-wide analysis led to the characterization of a new locus, DFNB40, which maps to an approximately 9 Mb interval between markers D22S427 and D22S1144 at chromosome 22q11.21-12.1. Maximum lod score of 3.09 was obtained with D22S1174. Since the Bronx waltzer (bv) mouse mutant, characterized by waltzing behavior, deafness, and degeneration of cochlear inner hair cells, has been mapped to the syntenic region on murine chromosome 5, we suggest that DFNB40 and bv may result from orthologous gene defects. 相似文献
9.
Refined mapping of the autosomal recessive non-syndromic deafness locus DFNB13 using eight novel microsatellite markers 总被引:1,自引:0,他引:1
Masmoudi S Charfedine I Rebeh IB Rebai A Tlili A Ghorbel AM Belguith H Petit C Drira M Ayadi H 《Clinical genetics》2004,66(4):358-364
The locus for a type of an autosomal recessive non-syndromic deafness (ARND), DFNB13, was previously mapped to a 17-cm interval of chromosome 7q34-36. We identified two consanguineous Tunisian families with severe to profound ARND. Linkage analyses with microsatellites surrounding the previously identified loci detected linkage with markers corresponding to the DFNB13 locus in both families. Haplotype analyses assigned this locus to a 3.2-Mb region between markers D7S2468 and D7S2473. In order to refine this interval, we identified nine dinucleotide repeats in the 7q34 region. To investigate the polymorphism of these repeats, a population study of 74 unrelated individuals from different regions of Tunisia was carried out. Our results demonstrated that eight of the nine repeats are polymorphic. The average number of alleles at these informative loci was 9.12 with a polymorphism information content of 0.71. Little evidence for linkage disequilibrium between some marker pairs was found. Haplotype analysis using these microsatellites refined the DFNB13 interval to an area of 2.2 Mb between the D7S5377 and D7S2473. In order to identify the DFNB13 gene, we sequenced and eliminated three candidate genes. Other known and predicted genes are being screened for deafness-causing mutations. 相似文献
10.
Map refinement of the Usher syndrome type 1B gene, MYO7A, relative to 11q13.5 microsatellite markers 总被引:1,自引:0,他引:1
Yolla Bou Mouglabey Sawsan Nimri Fouad Sayegh Elie El Zir Rima Slim 《Clinical genetics》1998,54(2):155-158
Usher syndrome (US) is clinically and genetically a heterogeneous group of disorders characterized by the association of deafness with retinitis pigmentosa. So far, eight genes responsible for US have been mapped, of which only the gene responsible for the most common form, USH1B, has been identified. The USH1B is a large gene containing 49 exons and encoding for an unconventional myosin-VIIA (MYO7A). Mutation analysis within the MYO7A gene showed a wide variety of mutations dispersed all over the gene. The present report refines the location of the MYO7A gene relative to microsatellite markers mapped to this region, thereby allowing a reliable and efficient carrier detection by linkage analysis. 相似文献
11.
Mapping of DFNB12, a gene for a non-syndromal autosomal recessive deafness, to chromosome 10q21-22 总被引:3,自引:0,他引:3
Chaib H; Place C; Salem N; Dode C; Chardenoux S; Weissenbach J; el Zir E; Loiselet J; Petit C 《Human molecular genetics》1996,5(7):1061-1064
We report here, the localization of a new recessive non-syndromal deafness
gene (DFNB12) to 10q21-22 by linkage analysis, of a Sunni family. Affected
individuals suffer from congenital profound sensorineural hearing loss. A
maximum LOD score of 6.40 (theta = 0.00) was obtained with locus D10S535.
Analysis of patients carrying recombinations mapped the gene distal to
D10S529 and proximal to D10S532, delineating an interval between 11 and 15
cM. Three deaf mouse mutants Jackson circler (jc), Waltzer (v) and Ames
waltzer (av) have been localized to the homologous murine region on
chromosome 10. Each of these mouse mutants is a candidate mouse model for
the DFNB12- associated hearing impairment.
相似文献
12.
Hadj-Rabia S Salomon R Pelet A Penet C Rotschild A de Laët MH Chaouachi B Hannachi R Bakiri F Brauner R Chaussain JL Munnich A Lyonnet S 《European journal of human genetics : EJHG》2000,8(8):613-620
Triple A syndrome (Allgrove syndrome, MIM No. 231550) is a rare autosomal recessive disorder characterised by ACTH-resistant adrenal insufficiency, achalasia of the cardia, and alacrimia. The triple A gene has been previously mapped to chromosome 12q13 in a maximum interval of 6 cM between loci D12S1629 and D12S312. Using linkage analysis in 12 triple A families, mostly originating from North Africa, we confirm that the disease locus maps to the 12q13 region (Zmax = 10.89 at theta = 0 for D12S1604) and suggest that triple A is a genetically homogeneous disorder. Recombination events as well as homozygosity for polymorphic markers enabled us to reduce the genetic interval to a 3.9 cM region. Moreover, total linkage disequilibrium was found at the D12S1604 locus between a rare allele and the mutant chromosomes in North African patients. Analysis of markers at five contiguous loci showed that most of the triple A chromosomes are derived from a single founder chromosome. As all markers are located in a 0 cM genetic interval and only allele 5 at the D12S1604 locus was conserved in mutant chromosomes, we speculate that the triple A mutation is due to an ancient Arabian founder effect that occurred before migration to North Africa. Since we also found linkage disequilibrium at D12S1604 in two patients from Southern Europe (France and Spain), the founder effect might well extend to other Mediterranean countries. Taking advantage of a YAC contig encompassing the triple A minimal physical region, the triple A gene was mapped to a 1.7 Mb DNA fragment accessible to gene cloning. 相似文献
13.
Lo Nigro C Cusano R Gigli GL Forabosco P Valente M Ravazzolo R Diomedi M Seri M 《American journal of medical genetics. Part A》2003,(2):116-121
We have recently mapped a new rare form of spastic paraplegia complicated by bilateral cataracts, gastroesophageal reflux with persistent vomiting, and amyotrophy to chromosome 10q23.3-q24.2. This locus, named SPG9, is located in an interval spanning about 12 cM of genomic DNA, between markers D10S536 and D10S603, where different neurological disorders have been mapped. In particular, a gene for partial epilepsy has been assigned to a 3 cM interval between markers D10S185 and D10S577, which is completely included in the SPG9 critical region. A few families affected with spastic paraplegia and epilepsy have been reported; in the present study, we tested a pedigree with concurrence of spastic paraplegia, epilepsy, and mental retardation inherited as an autosomal dominant trait, using markers located in the SPG9 interval. Haplotype reconstruction excluded the linkage to 10q23.3-q24.2. In addition, the seven different loci so far reported to be associated with autosomal dominant pure forms of spastic paraplegia have been tested and excluded by linkage analysis and haplotype reconstruction, including SPG4 on chromosome 2p22-p21, where a familial form of spastic paraplegia associated with dementia and epilepsy has been mapped. These data confirm genetic heterogeneity in familial spastic paraplegia with epilepsy and suggest a specific locus for the family here analyzed. 相似文献
14.
Two frequent missense mutations in Pendred syndrome 总被引:8,自引:3,他引:8
Van Hauwe P; Everett LA; Coucke P; Scott DA; Kraft ML; Ris-Stalpers C; Bolder C; Otten B; de Vijlder JJ; Dietrich NL; Ramesh A; Srisailapathy SC; Parving A; Cremers CW; Willems PJ; Smith RJ; Green ED; Van Camp G 《Human molecular genetics》1998,7(7):1099-1104
Pendred syndrome is an autosomal recessive disorder characterized by early
childhood deafness and goiter. A century after its recognition as a
syndrome by Vaughan Pendred, the disease gene ( PDS ) was mapped to
chromosome 7q22-q31.1 and, recently, found to encode a putative sulfate
transporter. We performed mutation analysis of the PDS gene in patients
from 14 Pendred families originating from seven countries and identified
all mutations. The mutations include three single base deletions, one
splice site mutation and 10 missense mutations. One missense mutation
(L236P) was found in a homozygous state in two consanguineous families and
in a heterozygous state in five additional non-consanguineous families.
Another missense mutation (T416P) was found in a homozygous state in one
family and in a heterozygous state in four families. Pendred patients in
three non-consanguineous families were shown to be compound heterozygotes
for L236P and T416P. In total, one or both of these mutations were found in
nine of the 14 families analyzed. The identification of two frequent PDS
mutations will facilitate the molecular diagnosis of Pendred syndrome.
相似文献
15.
Masmoudi S Tlili A Majava M Ghorbel AM Chardenoux S Lemainque A Zina ZB Moala J Männikkö M Weil D Lathrop M Ala-Kokko L Drira M Petit C Ayadi H 《European journal of human genetics : EJHG》2003,11(2):185-188
Approximately 80% of the hereditary hearing loss is nonsyndromic. Isolated deafness is the most genetically heterogeneous trait. We have ascertained 10 individuals from a large consanguineous Tunisian family with congenital profound autosomal recessive deafness. All affected individuals are otherwise healthy. Genotype analysis excluded linkage to known recessive deafness loci in this family. Following a genome wide screening, a linkage was detected only with locus D1S206 on chromosome 1, thereby defining a novel deafness locus, DFNB32. In order to confirm linkage and for fine mapping the genetic interval, 12 individuals belonging to this family were added and 19 microsatellite markers were tested. A maximum two-point lodscore of 4.96 was obtained at a new polymorphic marker D1S21401. Haplotype analysis defined a 16 Mb critical region between D1S2868 and afmb014zb9. The interval of DFNB32 locus overlap with DFNA37 locus and the Marshall and Stickler syndromes locus. The entire coding region of COL11A1, responsible of the later syndromes, was screened and no mutation was observed. Towards the identification of the DFNB32 gene, a search on the Human Cochlear cDNA Library and EST Database was done. The genes corresponding to the ESTs found in the DFNB32 interval are being screened for deafness-causing mutations. 相似文献
16.
Tariq A Santos RL Khan MN Lee K Hassan MJ Ahmad W Leal SM 《Journal of molecular medicine (Berlin, Germany)》2006,84(6):484-490
Autosomal recessive nonsyndromic hearing impairment (ARNSHI) is the most frequent form of prelingual hereditary hearing loss in humans. Between 75 and 80% of all nonsyndromic deafness is inherited in an autosomal recessive pattern. Using linkage analysis, we have mapped a novel gene responsible for this form of nonsyndromic hearing impairment, DFNB65, in a consanguineous family from the Azad Jammu and Kashmir regions, which border Pakistan and India. A maximum multipoint LOD score of 3.3 was obtained at marker D20S840. The three-unit support interval is contained between markers D20S902 and D20S430, while the region of homozygosity is flanked by markers D20S480 and D20S430. The novel locus maps to a 10.5-cM region on chromosome 20q13.2–q13.32 and corresponds to a physical map distance of 4.3 Mb. DFNB65 represents the first ARNSHI locus to map to chromosome 20. 相似文献
17.
Hmani M Ghorbel A Boulila-Elgaied A Ben Zina Z Kammoun W Drira M Chaabouni M Petit C Ayadi H 《European journal of human genetics : EJHG》1999,7(3):363-367
Usher type II syndrome is defined by the association of retinitis pigmentosa, appearing in the late second to early third decade of life, with congenital moderate to severe non-progressive hearing loss. This double sensory impairment is not accompanied by vestibular dysfunction. To date, only one Usher type II locus, USH2A, at chromosome band 1q41, has been defined. Here, we demonstrate by linkage analysis, that the gene responsible for Usher type II syndrome in a Tunisian consanguineous family maps to chromosome 3 at position p23-24.2, thus providing definitive evidence for the genetic heterogeneity of the syndrome. A maximum lod score of 4.3 was obtained with the polymorphic microsatellite markers corresponding to loci D3S1578, D3S3647 and D3S3658. This maps the gene underlying USH2B to a chromosomal region which overlaps the interval defined for the non-syndromic sensorineural recessive deafness DFNB6, raising the possibility that a single gene underlies both defects. However, the audiometric features in the patients affected by USH2B and DFNB6 are very different. 相似文献
18.
A novel locus for alopecia with mental retardation syndrome (APMR2) maps to chromosome 3q26.2-q26.31
Wali A John P Gul A Lee K Chishti MS Ali G Hassan MJ Leal SM Ahmad W 《Clinical genetics》2006,70(3):233-239
Congenital alopecia may occur either alone or in association with ectodermal and other abnormalities. On the bases of such associations, several different syndromes featuring congenital alopecia can be distinguished. Alopecia with mental retardation syndrome (APMR) is a rare autosomal recessive disorder, clinically characterized by total or partial hair loss and mental retardation. In the present study, a five-generation Pakistani family with multiple affected individuals with APMR was ascertained. Patients in this family exhibited typical features of APMR syndrome. The disease locus was mapped to chromosome 3q26.2-q26.31 by carrying out a genome scan followed by fine mapping. A maximum two-point logarithm of odds (LOD) score of 2.93 at theta=0.0 was obtained at markers D3S3053 and D3S2309. Multipoint linkage analysis resulted in a maximum LOD score of 4.57 with several markers, which supports the linkage. The disease locus was flanked by markers D3S1564 and D3S2427, which corresponds to 9.6-cM region according to the Rutgers combined linkage-physical map of the human genome (build 35) and contains 5.6 Mb. The linkage interval of the APMR locus identified here does not overlap with the one described previously; therefore, this locus has been designated as APMR2. 相似文献
19.
Yan D Ke X Blanton SH Ouyang XM Pandya A Du LL Nance WE Liu XZ 《Journal of medical genetics》2006,43(2):170-174
Background
Non‐syndromic hearing loss is among the most genetically heterogeneous traits known in humans. To date, at least 50 loci for autosomal dominant non‐syndromic sensorineural hearing loss (ADNSSHL) have been identified by linkage analysis.Objective
To report the mapping of a novel autosomal dominant deafness locus on the long arm of chromosome 14 at 14q11.2‐q12, DFNA53, in a large multigenerational Chinese family with post‐lingual, high frequency hearing loss that progresses to involve all frequencies.Results
A maximum multipoint LOD score of 5.4 was obtained for marker D14S1280. The analysis of recombinant haplotypes mapped DFNA53 to a 9.6 cM region interval between markers D14S581 and D14S1021. Four deafness loci (DFNA9, DFNA23, DFNB5, and DFNB35) have previously been mapped to the long arm of chromosome 14. The critical region for DFNA53 contains the gene for DFNA9 but does not overlap with the regions for DFNB5, DFNA23, or DFNB35. Screening of the COCH gene (DFNA9), BOCT, EFS, and HSPC156 within the DFNA53 interval did not identify the cause for deafness in this family.Conclusions
Identifying the DFNA53 locus is the first step in isolating the gene responsible for hearing loss in this large multigeneration Chinese family. 相似文献20.
Further evidence for linkage of low-mid frequency hearing impairment to the candidate region on chromosome 4p16.3 总被引:1,自引:0,他引:1
We have investigated a three-generation family with an autosomal dominant low-mid frequency hearing loss. Audiograms show consistently a hearing threshold of 50+/-20 db hearing loss (HL) between 250 Hz and 1-2 kHz. Normal hearing level was reached between 3 and 6 kHz in all examined children. Adult patients show an additional hearing impairment (HI) in the mid and higher frequencies that seems to differ from presbyacusis. The HI is always bilateral and symmetrical. Genes causing non-syndromic autosomal-dominant deafness with HI in the low and mid frequencies were previously mapped to chromosome 4p16.3 (DFNA6, DFNA14) and chromosome 5q31 (DFNA1). After exclusion of linkage to DFNA1 on chromosome 5, we mapped the candidate gene region to the DFNA14 and DFNA6 loci, between the genetic markers D4S432 and D4S431, located on chromosome 4. This is a further family in which evident linkage of low-mid frequency HI to the candidate region on chromosome 4p16.3 has been found. 相似文献