共查询到20条相似文献,搜索用时 15 毫秒
1.
Hyun-Ju Cho Hong-Joon Park Maria Trexler Hanka Venselaar Kyu-Yup Lee Nahid G. Robertson Jeong-In Baek Beom Sik Kang Cynthia C. Morton Gert Vriend László Patthy Un-Kyung Kim 《Journal of molecular medicine (Berlin, Germany)》2012,90(11):1321-1331
Mutations in COCH have been associated with autosomal dominant nonsyndromic hearing loss (DFNA9) and are frequently accompanied by vestibular hypofunction. Here, we report identification of a novel missense mutation, p.F527C, located in the vWFA2 domain in members of a Korean family with late-onset and progressive hearing loss. To assess the molecular characteristics of this cochlin mutant, we constructed both wild-type and mutant cochlin constructs and transfected these into mammalian cell lines. Results of immunocytochemistry analysis demonstrated localization of the cochlin mutant in the endoplasmic reticulum/Golgi complex, whereas western blot analyses of cell lysates revealed that the mutant cochlin tends to form covalent complexes that are retained in the cell. Biochemical analyses of recombinant vWFA2 domain of cochlin carrying the p.F527C mutation revealed that the mutation increases propensity of the protein to form covalent disulfide-bonded dimers and affects the structural stability but not the collagen-affinity of the vWFA2 domain. We suggest that the instability of mutant cochlin is the major driving force for cochlin aggregation in the inner ear in DFNA9 patients carrying the COCH p.F527C mutation. 相似文献
2.
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
3.
Gingival fibromatosis is a heterogeneous entity that can occur both as a part of syndromes and as an isolated trait. We describe the second family with a rare, dominantly inherited syndrome of gingival fibromatosis and progressive sensorineural hearing loss. 相似文献
4.
5.
Donaudy F Zheng L Ficarella R Ballana E Carella M Melchionda S Estivill X Bartles JR Gasparini P 《Journal of medical genetics》2006,43(2):157-161
Background
Espins are actin bundling proteins present in hair cell stereocilia. A recessive mutation in the espin gene (Espn) has been detected in the jerker mouse and causes deafness, vestibular dysfunction, and hair cell degeneration. More recently mutations in the human espin gene (ESPN) have been described in two families affected by autosomal recessive hearing loss and vestibular areflexia.Objective
To report the identification of four additional ESPN mutations (S719R, D744N, R774Q, and delK848) in patients affected by autosomal dominant hearing loss without vestibular involvement.Results
To determine whether the mutated ESPN alleles affected the biological activity of the corresponding espin proteins in vivo, their ability to target and elongate the parallel actin bundles of brush border microvilli was investigated in transfected LLC‐PK1‐CL4 epithelial cells. For three mutated alleles clear abnormalities in microvillar length or distribution were obtained.Conclusions
The results further strengthen the causative role of the espin gene in non‐syndromic hearing loss and add new insights into espin structure and function. 相似文献6.
Se-Kyung Oh Jeong-In Baek Karl M Weigand Hanka Venselaar Herman G P Swarts Seong-Hyun Park Muhammad Hashim Raza Da Jung Jung Soo-Young Choi Sang-Heun Lee Thomas Friedrich Gert Vriend Jan B Koenderink Un-Kyung Kim Kyu-Yup Lee 《European journal of human genetics : EJHG》2015,23(5):639-645
Hereditary sensorineural hearing loss is an extremely clinical and genetic heterogeneous disorder in humans. Especially, syndromic hearing loss is subdivided by combinations of various phenotypes, and each subtype is related to different genes. We present a new form of progressive hearing loss with migraine found to be associated with a variant in the ATP1A2 gene. The ATP1A2 gene has been reported as the major genetic cause of familial migraine by several previous studies. A Korean family presenting progressive hearing loss with migraine was ascertained. The affected members did not show any aura or other neurologic symptoms during migraine attacks, indicating on a novel phenotype of syndromic hearing loss. To identify the causative gene, linkage analysis and whole-exome sequencing were performed. A novel missense variant, c.571G>A (p.(Val191Met)), was identified in the ATP1A2 gene that showed co-segregation with the phenotype in the family. In silico studies suggest that this variant causes a change in hydrophobic interactions and thereby slightly destabilize the A-domain of Na+/K+-ATPase. However, functional studies failed to show any effect of the p.(Val191Met) substitution on the catalytic rate of this enzyme. We describe a new phenotype of progressive hearing loss with migraine associated with a variant in the ATP1A2 gene. This study suggests that a variant in Na+/K+-ATPase can be involved in both migraine and hearing loss. 相似文献
7.
A novel C202F mutation in the connexin26 gene (GJB2) associated with autosomal dominant isolated hearing loss 下载免费PDF全文
Morlé L Bozon M Alloisio N Latour P Vandenberghe A Plauchu H Collet L Edery P Godet J Lina-Granade G 《Journal of medical genetics》2000,37(5):368-370
Mutations in the GJB2 gene encoding connexin26 (CX26) account for up to 50% of cases of autosomal recessive hearing loss. In contrast, only one GJB2 mutation has been reported to date in an autosomal dominant form of isolated prelingual hearing loss. We report here a novel heterozygous 605G→T mutation in GJB2 in all affected members of a large family with late childhood onset of autosomal dominant isolated hearing loss. The resulting C202F substitution, which lies in the fourth (M4) transmembrane domain of CX26, may impair connexin oligomerisation. Finally, our study suggests that GJB2 should be screened for heterozygous mutations in patients with autosomal dominant isolated hearing impairment, whatever the severity of the disease.
Keywords: C202F mutation; connexin26 gene (GJB2); autosomal dominant hearing loss 相似文献
Keywords: C202F mutation; connexin26 gene (GJB2); autosomal dominant hearing loss 相似文献
8.
Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss 总被引:4,自引:0,他引:4
Analysis of genotyping of a five-generation American family with nonsyndromic dominant progressive hearing loss indicated linkage to the DFNA2 locus on chromosome 1p34. This kindred consists of 170 individuals, of which 51 are affected. Pure tone audiograms, medical records, and blood samples were obtained from 36 family members. Linkage analysis with five microsatellite markers spanning the region around DFNA2 produced a lod score of 6.6 for the marker MYCL1 at straight theta = 0.0. Hearing loss in this family showed a very similar pattern as the first reported American family with the same linkage. High frequency hearing loss was detectable as early as 3 years of age, and progressed to severe to profound loss by the fourth decade. Using intronic primers, we screened the coding region of the KCNQ4 gene. Heteroduplex analysis followed by direct sequencing identified a T-->C transition at position 842, which would produce an L281S amino acid substitution. The observed mutation was shown to segregate completely with affected status in this family. The L281 residue is significantly conserved among the other members of the voltage-gated K(+) channel genes superfamily. Hydrophobicity analysis indicated that L281S substitution would lower formation of the beta structure at the P region of this ion channel. Mutation analysis of KCNQ4 was also performed on 80 unrelated probands from families with recessive or dominant nonsyndromic hearing loss. None of these cases showed a truncated mutation in KCNQ4. 相似文献
9.
Sixteen Japanese nonsyndromic autosomal dominant sensorineural hearing loss (ADSNHL) families were investigated clinically
as well as genetically. Most families showed postlingual hearing loss. Although the severity of their hearing loss varied,
most patients showed mild-moderate sensorineural hearing loss of a progressive nature. Mutation analysis was performed for
the MYO7A, KCNQ4, and GJB3 genes, which are known to be responsible for autosomal dominant sensorineural hearing loss. The present study reports that
a mutation in KCNQ4, a member of a large family of potassium channel genes, was responsible for ADSNHL in one Japanese family.
Received: January 16, 2001 / Accepted: March 15, 2001 相似文献
10.
A gene for autosomal dominant late-onset progressive non-syndromic hearing loss, DFNA10, maps to chromosome 6 总被引:5,自引:1,他引:4
O'Neill ME; Marietta J; Nishimura D; Wayne S; Van Camp G; Van Laer L; Negrini C; Wilcox ER; Chen A; Fukushima K; Ni L; Sheffield VC; Smith RJ 《Human molecular genetics》1996,5(6):853-856
Late-onset non-syndromic hearing impairment is the most common type of
neurological dysfunction in the elderly. It can be either acquired or
inherited, although the relative impact of heredity on this type of loss is
not known. To date, nine different genes have been localized, but none has
been cloned. Using an extended American family in which a gene for
autosomal dominant late-onset non-syndromic hearing impairment is
segregating, we have identified a new locus, DFNA10, on chromosome 6.
相似文献
11.
Alloisio N Morlé L Bozon M Godet J Verhoeven K Van Camp G Plauchu H Muller P Collet L Lina-Granade G 《European journal of human genetics : EJHG》1999,7(2):255-258
A gene responsible for autosomal dominant non-syndromic hearing impairment in two families (DFNA8 and DFNA12) has recently been identified as TECTA encoding alpha-tectorin, a major component of the tectorial membrane. In these families, missense mutations within the zona pellucida domain of alpha-tectorin were associated with stable severe mid-frequency hearing loss. The present study reports linkage to DFNA12 in a new family with autosomal dominant high frequency hearing loss progressing from mild to moderate severity. The candidate region refined to 3.8 cM still contained the TECTA gene. A missense mutation (C1619S) was identified in the zonadhesin-like domain. This mutation abolishes the first of the vicinal cysteines (1619Cys-Gly-Leu- 1622Cys) present in the D4 von Willebrand factor (vWf) type D repeat. These results further support the involvement of TECTA mutations in autosomal dominant hearing impairment, and suggest that vicinal cysteines are involved in tectorial membrane matrix assembly. 相似文献
12.
Identification of a novel missense mutation in the WFS1 gene as a cause of autosomal dominant nonsyndromic sensorineural hearing loss in all‐frequencies 下载免费PDF全文
Xiaohui Bai Huaiqing Lv Fengguo Zhang Jinzhi Liu Zhaomin Fan Lei Xu Yuhang Han Renjie Chai Jianfeng Li Haibo Wang 《American journal of medical genetics. Part A》2014,164(12):3052-3060
13.
14.
Najmabadi H Cucci RA Sahebjam S Kouchakian N Farhadi M Kahrizi K Arzhangi S Daneshmandan N Javan K Smith RJ 《Human mutation》2002,19(5):572
Hereditary hearing loss (HHL) is an extremely common disorder. About 70% of HHL is non-syndromic, with autosomal recessive forms accounting for approximately 85% of the genetic load. Although very heterogeneous, the most common cause of HHL in many different world populations is mutations of GJB2, a gene that encodes the gap junction protein connexin 26 (Cx26). This study investigates the contribution of GJB2 to the autosomal recessive non-syndromic deafness (ARNSD) load in the Iranian population. One hundred sixty eight persons from 83 families were studied. GJB2-related deafness was diagnosed in 9 families (4, 35delG homozygotes; 3, 35delG compound heterozygotes; 1, W24X homozygote; 1, non-35delG compound heterozygote). The carrier frequency of the 35delG allele in this population was approximately 1% (1/83). Because the relative frequency of Cx26 mutations is much less than in the other populations, it is possible that mutations in other genes play a major role in ARNSD in Iran. 相似文献
15.
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
16.
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
17.
A Moroccan family with autosomal recessive sensorineural hearing loss caused by a mutation in the gap junction protein gene connexin 26 (GJB2). 总被引:2,自引:2,他引:2 下载免费PDF全文
N J Lench A F Markham R F Mueller D P Kelsell R J Smith P J Willems I Schatteman H Capon P J Van De Heyning G Van Camp 《Journal of medical genetics》1998,35(2):151-152
We report a mutation in the connexin 26 gene (Cx26) in a consanguineous Moroccan family linked to the DFNA3/DFNB1 locus on human chromosome 13q11-q12. Affected subjects display congenital, bilateral, sensorineural hearing loss. We have previously identified Cx26 mutations in consanguineous Pakistani families. This current finding indicates that Cx26 mutations are not restricted to ethnically and geographically distinct populations. This is an important observation since it will help to determine the overall contribution of connexin 26 mutations to autosomal deafness in different populations. 相似文献
18.
Yibo Yu Yinhui Yu Peiqing Chen Jinyu Li Yanan Zhu Yi Zhai Ke Yao 《BMC medical genetics》2014,15(1):1-7
Background
The major intrinsic protein gene (MIP), also known as MIP26 or AQP0, is a member of the water-transporting aquaporin family, which plays a critical role in the maintenance of lifelong lens transparency. To date, several mutations in MIP (OMIM 154050) have been linked to hereditary cataracts in humans. However, more pathogenic mutations remain to be identified. In this study, we describe a four-generation Chinese family with a nonsense mutation in MIP associated with an autosomal dominant congenital cataract (ADCC), thus expanding the mutational spectrum of this gene.Methods
A large four-generation Chinese family affected with typical Y-suture cataracts combined with punctuate cortical opacities and 100 ethnically matched controls were recruited. Genomic DNA was extracted from peripheral blood leukocytes to analyze congenital cataract-related candidate genes. Effects of the sequence change on the structure and function of proteins were predicted by bioinformatics analysis.Results
Direct sequencing of MIP in all affected members revealed a heterozygous nucleotide exchange c.337C>T predicting an arginine to a stop codon exchange (p.R113X). The substitution co-segregated well in all the affected individuals in the family and was not found in unaffected members or in the 100 unrelated healthy controls. Bioinformatics analysis predicted that the mutation affects the secondary structure and function of the MIP protein.Conclusions
We identified a novel mutation of MIP (p.R113X) in a Chinese cataract family. This is the first nonsense mutation of MIP identified thus far. This novel mutation is also the first disease-causing mutation located in the loop C domain of MIP. The results add to the list of mutations of the MIP linked to cataracts. 相似文献19.
Hereditary deafness is a genetically heterogeneous phenotype for which more than 100 genomic loci have been identified thus far. By analysis of a consanguineous Palestinian family, GPSM2 was recently discovered to be the cause of autosomal recessive non-syndromic hearing loss DFNB82. Here, we report a second truncating mutation, GPSM2 p.Q562X, identified via autozygosity mapping in a consanguineous Turkish family. This report provides evidence for allelic heterogeneity of GPSM2 and confirms its causative role for non-syndromic deafness. 相似文献
20.
Sanggaard KM Kjaer KW Eiberg H Nürnberg G Nürnberg P Hoffman K Jensen H Sørum C Rendtorff ND Tranebjaerg L 《American journal of medical genetics. Part A》2008,(8):1017-1025
Autosomal dominant inheritance is described in about 20% of all nonsyndromic hearing loss with currently 54 distinct loci (DFNA1-54), and >20 different genes identified. Seven different unconventional myosin genes are involved in ten different types of syndromic and nonsyndromic hearing loss with different patterns of inheritance: MYO7A in DFNA11/DFNB2/USH1B, MYH9 in DFNA17, MYH14 in DFNA4, MYO6 in DFNA22/DFNB37, MYO3A in DFNB30, MYO1A in DFNA48, and MYO15A in DFNB3. Two missense mutations in MYO6 (p.C442Y and p.H246R) have been characterized in families of Italian and American Caucasian extraction with autosomal dominant hearing loss, respectively, and the latter was associated with cardiomyopathy in some patients. Three Pakistani families had homozygosity for three MYO6 mutations (c.36insT, p.R1166X, and p.E216V, respectively), and was in one instance associated with retinal degeneration. In the present study, we linked autosomal dominant hearing loss in a large Danish family to a 38.9 Mb interval overlapping with the DFNA22/DFNB37 locus on chromosome 6q13. A novel nonsense mutation in MYO6 exon 25 (c.2545C > T; p.R849X) was identified in the family. The mutation co-segregated with the disease and the mutant allele is predicted to encode a truncated protein lacking the coiled-coil and globular tail domains. These domains are hypothesized to be essential for targeting myosin VI to its cellular compartments. No other system was involved indicating nonsyndromic loss. In conclusion, a novel nonsense MYO6 mutation causes post-lingual, slowly progressive autosomal dominant nonsyndromic moderate to severe hearing loss in a Danish family. 相似文献