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1.
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2.
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
3.
Meyer CG Gasmelseed NM Mergani A Magzoub MM Muntau B Thye T Horstmann RD 《Human mutation》2005,25(1):100
Mutations of the transmembrane channel-like gene 1 (TMC1) have been shown to cause autosomal dominant and recessive forms of congenital nonsyndromic deafness linked to the loci DFNA36 and DFNB7/B11, respectively. In a Sudanese pedigree affected by an apparently recessive form of nonsyndromic deafness, we performed a linkage analysis using markers covering the deafness loci DFNB1 - DFNB30. A two-point LOD score of 3.08 was obtained at marker position D9S1876, located within the first intron of the TMC1 gene at DFNB7/B11. By DNA sequencing of TMC1 exons 3-22, we identified the structural variant c.1165C>T in exon 13, leading to the stop codon p.Arg389X, and the splice-site variant c.19+5G>A, independently segregating with the deafness phenotype. The c.1165C>T [p.Arg389X] mutation was also observed in four out of 243 unrelated deaf Sudanese individuals, but none of the mutations was found among 292 normal hearing controls. The finding of TMC1 mutations contributing to deafness in Sudan confirms and extends previous reports on the role of TMC1 in recessive nonsyndromic deafness and shows that deafness-causing TMC1 mutations may occur in various ethnic groups. 相似文献
4.
Mustapha M Chouery E Chardenoux S Naboulsi M Paronnaud J Lemainque A Mégarbané A Loiselet J Weil D Lathrop M Petit C 《European journal of human genetics : EJHG》2002,10(3):210-212
We report the identification of a novel locus responsible for an autosomal recessive form of hearing loss (DFNB) segregating in a Palestinian consanguineous family from Jordan. The affected individuals suffer from profound prelingual sensorineural hearing impairment. A genetic linkage with polymorphic markers surrounding D9S1776 was detected, thereby identifying a novel deafness locus, DFNB31. This locus could be assigned to a 9q32-34 region of 15 cM between markers D9S289 and D9S1881. The whirler (wi) mouse mutant, characterised by deafness and circling behaviour, maps to the corresponding region on the murine chromosome 4, thus suggesting that DFNB31 and whirler may result from orthologous gene defects. 相似文献
5.
Aslam M Wajid M Chahrour MH Ansar M Haque S Pham TL Santos RP Yan K Ahmad W Leal SM 《American journal of medical genetics. Part A》2005,(1):18-22
A consanguineous family with autosomal recessive nonsyndromic hearing impairment (NSHI) was ascertained in Pakistan and displayed significant evidence of linkage to 3q13.31-q22.3. The novel locus (DFNB42) segregating in this kindred, maps to a 21.6 cM region according to a genetic map constructed using data from both the deCode and Marshfield genetic maps. This region of homozygosity is flanked by markers D3S1278 and D3S2453. A maximum multipoint LOD score of 3.72 was obtained at marker D3S4523. DFNB42 represents the third autosomal recessive NSHI locus to map to chromosome 3. 相似文献
6.
Pulleyn LJ Jackson AP Roberts E Carridice A Muxworthy C Houseman M Al-Gazali LI Lench NJ Markham AF Mueller RF 《European journal of human genetics : EJHG》2000,8(12):991-993
Non-syndromic sensorineural deafness is an extremely genetically heterogeneous condition. We have used autozygosity mapping in a large consanguineous United Arab Emirate family to identify a novel locus for autosomal recessive non-syndromic sensorineural deafness, DFNB27, on chromosome 2q23-q31, with a maximum two-point lod score of 5.18 at theta = 0 for marker D2S2257. The DFNB27 locus extends over a 17 cM region between D2S2157 and D2S2273, and may overlap the DFNA16 locus for dominantly inherited, fluctuating, progressive non-syndromal hearing loss. However, genotype data suggests that the locus is likely to be refined to between D2S326 and D2S2273 and thus distinct from the DFNA16 locus. 相似文献
7.
AM Waryah A Rehman ZM Ahmed Z-H Bashir SY Khan AU Zafar S Riazuddin TB Friedman S Riazuddin 《Clinical genetics》2009,76(3):270-275
Autosomal recessive nonsyndromic hearing impairment (ARNSHI) segregating in three unrelated, large consanguineous Pakistani families (PKDF528, PKDF859 and PKDF326) is linked to markers on chromosome 12q14.2-q15. This novel locus is designated DFNB74 . Maximum two-point limit of detection (LOD) scores of 5.6, 5.7 and 2.6 were estimated for markers D 12 S 313, D 12 S 83 and D 12 S 75 at θ = 0 for recessive deafness segregating in these three families. Haplotype analyses identified a critical linkage interval of 5.35 cM (5.36 Mb) defined by D 12 S 329 at 74.58 cM and D 12 S 313 at 79.93 cM. DFNB74 is the second ARNSHI locus mapped to chromosome 12, but the physical intervals do not overlap with one another. A locus contributing to the early onset, rapidly progressing hearing loss of A/J mice ( ahl4 , age-related hearing loss 4) was reported to map to chromosome 10 in a region of conserved synteny to DFNB74 , suggesting that ahl4 and DFNB74 may be due to mutations of the same gene in these two species. 相似文献
8.
A new locus for non-syndromal, autosomal recessive, sensorineural hearing loss (DFNB16) maps to human chromosome 15q21-q22. 下载免费PDF全文
D A Campbell D P McHale K A Brown L M Moynihan M Houseman G Karbani G Parry A H Janjua V Newton L al-Gazali A F Markham N J Lench R F Mueller 《Journal of medical genetics》1997,34(12):1015-1017
Non-syndromal, recessive deafness (NSRD) is the most common form of inherited deafness or hearing impairment in humans. NSRD is genetically heterogeneous and it has been estimated that as many as 35 different loci may be involved. We report the mapping of a novel locus for autosomal recessive, non-syndromal deafness (DFNB16) in three consanguineous families originating from Pakistan and the Middle East. Using multipoint analysis (HOMOZ/MAPMAKER) a maximum combined lod score of 6.5 was obtained for the interval D15S1039-D15S123. Recombination events and haplotype analysis define a 12-14 cM critical region between the markers D15S1039 and D15S155 on chromosome 15q15-q21. 相似文献
9.
Wajid M Abbasi AA Ansar M Pham TL Yan K Haque S Ahmad W Leal SM 《European journal of human genetics : EJHG》2003,11(10):812-815
This article describes the identification of a novel locus (DFNB39) responsible for an autosomal recessive form of hearing loss segregating in a Pakistani consanguineous family. The hearing impaired members of this family present with profound prelingual sensorineural hearing impairment and use sign language for communications. Linkage was established to microsatellite markers located on chromosome 7q with a maximum multipoint lod score of 3.8. The region of homozygosity spans a 19 cM region that is bounded by markers D7S3046 and D7S644. 相似文献
10.
Mir A Ansar M Chahrour MH Pham TL Wajid M Haque S Yan K Ahmad W Leal SM 《American journal of medical genetics. Part A》2005,(1):23-26
Hereditary nonsyndromic deafness (NSD) is extremely heterogeneous. Autosomal recessive (AR) forms account for approximately 75% of genetic cases. To date, over 40 ARNSD loci have been mapped. A novel locus (DFNB46) for ARNSD was mapped to chromosome 18p11.32-p11.31 in a five-generation Pakistani family. A 10 cM genome-wide scan and fine mapping was carried out using microsatellite markers. A maximum multipoint LOD score of 3.8 was obtained at two markers, D18S481 and D18S1370. The three-unit support interval is flanked by markers D18S59 and D18S391, corresponds to a 17.6 cM region according to the deCode genetic map and spans 5.8 Mb on the sequence-based physical map. 相似文献
11.
Kalay E Karaguzel A Caylan R Heister A Cremers FP Cremers CW Brunner HG de Brouwer AP Kremer H 《Human mutation》2005,26(6):591
Mutations in the transmembrane channel-like gene 1 (TMC1) cause prelingual autosomal recessive (DFNB7/11) and postlingual progressive autosomal dominant (DFNA36) nonsyndromic hearing loss. To determine the genetic causes of autosomal recessive nonsyndromic hearing loss (ARNSHL) in the northeast and east of Turkey, 65 unrelated families without mutations in the protein coding region of the GJB2 (GJB2-negative) were analyzed. A genomewide scan for homozygosity and linkage analysis in one of these families revealed a 13.2 cM critical region between D9S273 and D9S153 at chromosome 9p13.2-q21.31 with a maximum two-point lod score of 4.00 at theta=0.0 for marker D9S175. TMC1 is in this critical region. Homozygosity screening with intragenic markers for TMC1 in the remaining 64 families suggested involvement of this gene in three additional families. Subsequent sequencing of TMC1 in these four families revealed four novel homozygous mutations, c.776A>G [p.Tyr259Cys], c.821C>T [p.Pro274Leu], c.1334G>A [p.Arg445His], and c.1083_1087delCAGAT [p.Arg362ProfrX6]. Our results indicate that TMC1 mutations account for at least 6% (4/65) of ARNSHL in GJB2-negative Turkish families from the northeast and east of Turkey. 相似文献
12.
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
13.
Bazazzadegan N Sheffield AM Sobhani M Kahrizi K Meyer NC Van Camp G Hilgert N Abedini SS Habibi F Daneshi A Nishimura C Avenarius MR Farhadi M Smith RJ Najmabadi H 《American journal of medical genetics. Part A》2011,155(5):1202-1211
Mutations in GJB2, encoding connexin 26 (Cx26), cause both autosomal dominant and autosomal recessive nonsyndromic hearing loss (ARNSHL) at the DFNA3 and DFNB1 loci, respectively. Most of the over 100 described GJB2 mutations cause ARNSHL. Only a minority has been associated with autosomal dominant hearing loss. In this study, we present two families with autosomal dominant nonsyndromic hearing loss caused by a novel mutation in GJB2 (p.Asp46Asn). Both families were ascertained from the same village in northern Iran consistent with a founder effect. This finding implicates the D46N missense mutation in Cx26 as a common cause of deafness in this part of Iran mandating mutation screening of GJB2 for D46N in all persons with hearing loss who originate from this geographic region. 相似文献
14.
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
15.
Xia J Deng H Feng Y Zhang H Pan Q Dai H Long Z Tang B Deng H Chen Y Zhang R Zheng D He Y Xia K 《Journal of human genetics》2002,47(12):0635-0640
Hearing impairment is an extremely heterogeneous disorder. A total of 35 loci and 17 related genes for autosomal dominant
nonsyndromic hearing loss have been identified. In a Chinese pedigree characterized by autosomal dominant inheritance with
bilateral, postlingual, progressive, and sensorineural nonsyndromic hearing impairment, the putative disease gene locus was
localized to chromosome 5q31.1-32 by a genome-wide scan. Fine mapping indicated that the disease gene was located within an
8.8-cM region between markers D5S2056 and D5S638, with a maximum two-point logarithm of differences (LOD) score of 6.89 (θ = 0) at D5S2017. By the candidate gene approach, mutation screening of the DIAPH1 and POU4F3 genes at 5q31 was performed. No mutation was found, suggesting that this is a novel deafness locus, which has been named
DFNA42.
Received: May 8, 2002 / Accepted: October 1, 2002 相似文献
16.
Bönsch D Scheer P Neumann C Lang-Roth R Seifert E Storch P Weiller C Lamprecht-Dinnesen A Deufel T 《European journal of human genetics : EJHG》2001,9(3):165-170
Investigating a large German pedigree with non-syndromic hearing impairment of early onset and autosomal dominant mode of inheritance, linkage to known DFNA loci was excluded and in a subsequent genomic scan the phenotype was mapped to a 10-cM interval on chromosome 3q22; a maximum two-point lod score of 3.77 was obtained for the marker D3S1292. The new locus, DFNA18, is excluded from neighbouring deafness loci, DFNB15 and USH3, and it overlaps with the recently described DM2/PROMM locus. As hearing loss has been described as one feature of the PROMM phenotype, the DFNA18 gene might also be responsible for hearing loss in DM2/PROMM. 相似文献
17.
A gene for non-syndromic autosomal dominant progressive postlingual sensorineural hearing loss maps to chromosome 14q12-13 总被引:12,自引:1,他引:12
Manolis EN; Yandavi N; Nadol JB Jr; Eavey RD; McKenna M; Rosenbaum S; Khetarpal U; Halpin C; Merchant SN; Duyk GM; MacRae C; Seidman CE; Seidman JG 《Human molecular genetics》1996,5(7):1047-1050
We report a novel locus responsible for postlingual progressive
sensorineural hearing loss (designated DFNA9) that maps to chromosome
14q12-13. A large kindred with autosomal dominant transmission of non-
syndromic hearing loss was clinically studied. Hearing in affected
individuals deteriorated at approximately 20 years of age and progressed to
anacusis in the fifth decade. A random genome-wide search using polymorphic
short tandem repeats demonstrated linkage with D14S121 (maximum two point
LOD score = 6.19, theta = 0). Haplotype analysis of recombination events
defined a 9 cM disease interval, between D14S252 and D14S49.
相似文献
18.
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
19.
A novel locus for autosomal dominant non-syndromic deafness (DFNA41) maps to chromosome 12q24-qter 总被引:1,自引:0,他引:1
Blanton SH Liang CY Cai MW Pandya A Du LL Landa B Mummalanni S Li KS Chen ZY Qin XN Liu YF Balkany T Nance WE Liu XZ 《Journal of medical genetics》2002,39(8):567-570
We have studied 36 subjects in a large multigenerational Chinese family that is segregating for an autosomal dominant adult onset form of progressive non-syndromic hearing loss. All affected subjects had bilateral sensorineural hearing loss involving all frequencies with some significant gender differences in initial presentation. After excluding linkage to known loci for non-syndromic deafness, we used the Center for Inherited Disease Research (CIDR) to test for 351 polymorphic markers distributed at approximately 10 cM intervals throughout the genome. Analysis of the resulting data provided evidence that the locus designated DFNA41 maps to a 15 cM region on chromosome 12q24.32-qter, proximal to the marker D12S1609. A maximum two point lod score of 6.56 at theta=0.0 was obtained for D12S343. This gene is distal to DFNA25, a previously identified locus for dominant adult onset hearing loss that maps to 12q21-24. Positional/functional candidate genes in this region include frizzled 10, epimorphin, RAN, and ZFOC1. 相似文献
20.
Hearing loss is a common sensory deficit in humans. The hearing loss may be conductive, sensorineural, or mixed, syndromic or nonsyndromic, prelingual or postlingual. Due to the complexity of the hearing mechanism, it is not surprising that several hundred genes might be involved in causing hereditary hearing loss. There are at least 82 chromosomal loci that have been identified so far which are associated with the most common type of deafness--non-syndromic deafness. However, there are still many more which remained to be discovered. Here, we report the mapping of a locus for autosomal recessive, non-syndromic deafness in a family in Malaysia. The investigated family (AC) consists of three generations--parents who are deceased, nine affected and seven unaffected children and grandchildren. The deafness was deduced to be inherited in an autosomal recessive manner with 70% penetrance. Recombination frequencies were assumed to be equal for both males and females. Using two-point lod score analysis (MLINK), a maximum lod score of 2.48 at 0% recombinant (Z = 2.48, theta = 0%) was obtained for the interval D14S63-D14S74. The haplotype analysis defined a 14.38 centiMorgan critical region around marker D14S258 on chromosome 14q23.2-q24.3. There are 16 candidate genes identified with positive expression in human cochlear and each has great potential of being the deaf gene responsible in causing non-syndromic hereditary hearing loss in this particular family. Hopefully, by understanding the role of genetics in deafness, early interventional strategies can be undertaken to improve the life of the deaf community. 相似文献