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1.
D. D. Nadyrshina R. I. Khusainova E. K. Khusnutdinova 《Russian Journal of Genetics》2012,48(3):321-328
Nucleotide sequences of exon 51, adjacent intron areas, and regulatory region of the α1 chain of type I collagen (COL1A1) gene were analyzed in 41 patients with osteogenesis imperfecta (OI) from 33 families and their 68 relatives residing at
Bashkortostan Republic (BR). Six mutations (four nonsense mutations c.967G>T (p.Gly323X), c.1081C>T (p.Arg361X), c.1243C>T
(p.Arg415X), and c.2869C>T (p.Gln957X)) in patients of the Russian origin and two frameshift mutations (c.579delT (p.Gly194ValfsX71),
and c.2444delG (p.Gly815AlafsX293)) in patients with OI of Tatar ethnicity as well as 14 single nucleotide polymorphisms in
the COL1A1 gene were revealed. Mutations c.967G>T (p.Gly323X) and three alterations in the nucleotide sequence c.544-24C>T, c.643-36delT,
and c.957 + 10insA were described for the first time. 相似文献
2.
Osteogenesis imperfecta (OI) is a generalised disorder of connective tissue characterised by an increased fragility of bones and also manifested in other tissues containing collagen type I, by blue sclera, hearing loss, dentinogenesis imperfecta, hyperextensible joints, hernias and easy bruising. OI is dominantly inherited and results in >90% OI cases, caused by mutations in one of the two genes COL1A1 or COL1A2 coding for type I procollagen. The Lithuanian OI database comprises 147 case records covering the period of 1980 - 2001. Clinical and genealogical analysis of OI cases/families from Lithuania available for examination revealed 18 familial cases of OI type I and 22 sporadic cases: OI type II (3 cases), OI type III (11 cases) and OI type I (8 cases). As a result of their molecular genetic investigation, 11 mutations were identified in the COL1A1 gene in 13 unrelated patients. Of them, nine mutations (E500X, G481A, c.2046insCTCTCTAG, c.1668delT, c.1667insC, c.4337insC, IVS19+1G > A, IVS20-2A > G, IVS22-1G > T) appeared to be novel, i.e. not yet registered in the Human Type I and Type III Collagen Mutations Database (http://www.le.ac.uk/genetics/collagen). 相似文献
3.
Zhenping Xu Yulei Li Xiangyang Zhang Fanming Zeng Mingxiong Yuan Mugen Liu Qing Kenneth Wang Jing Yu Liu 《遗传学报》2011,38(4):149-156
Osteogenesis imperfecta (OI, also known as brittle bone disease) is caused mostly by mutations in two type Ⅰ collagen genes, COL1A1 and COL1A2 encoding the pro-α1 (Ⅰ) and pro-α2 (Ⅰ) chains of type Ⅰ collagen, respectively. Two Chinese families with autosomal dominant OI were identified and characterized. Linkage analysis revealed linkage of both families to COL1A2 on chromosome 7q21.3-q22.1. Mutational analysis was carried out using direct DNA sequence analysis. Two novel missense mutations, c.3350A>G and c.3305G>C, were identified in exon 49 of COL1A2 in the two families, respectively. The c.3305G>C mutation resulted in substitution of a glycine residue (G) by an alanine residue (A) at codon 1102 (p.G1102A), which was found to be mutated into serine (S), argine (R), aspartic acid (D), or valine (V) in other families. The c.3350A>G variant may be a de novo mutation resulting in p.Y1117C. Both mutations co-segregated with OI in respective families, and were not found in 100 normal controls. The G1102 and Y1117 residues were evolutionarily highly conserved from zebrafish to humans. Mutational analysis did not identify any mutation in the COX-2 gene (a modifier gene of OI). This study identifies two novel mutations p.G1102A and p.Y1117C that cause OI, significantly expands the spectrum of COL1A2 mutations causing OI, and has a significant implication in prenatal diagnosis of OI. 相似文献
4.
Background
The genetics of osteogenesis imperfecta (OI) have not been studied in a Vietnamese population before. We performed mutational analysis of the COL1A1 and COL1A2 genes in 91 unrelated OI patients of Vietnamese origin. We then systematically characterized the mutation profiles of these two genes which are most commonly related to OI.Methods
Genomic DNA was extracted from EDTA-preserved blood according to standard high-salt extraction methods. Sequence analysis and pathogenic variant identification was performed with Mutation Surveyor DNA variant analysis software. Prediction of the pathogenicity of mutations was conducted using Alamut Visual software. The presence of variants was checked against Dalgleish’s osteogenesis imperfecta mutation database.Results
The sample consisted of 91 unrelated osteogenesis imperfecta patients. We identified 54 patients with COL1A1/2 pathogenic variants; 33 with COL1A1 and 21 with COL1A2. Two patients had multiple pathogenic variants. Seventeen novel COL1A1 and 10 novel COL1A2 variants were identified. The majority of identified COL1A1/2 pathogenic variants occurred in a glycine substitution (36/56, 64.3 %), usually serine (23/36, 63.9 %). We found two pathogenic variants of the COL1A1 gene c.2461G?>?A (p.Gly821Ser) in four unrelated patients and one, c.2005G?>?A (p.Ala669Thr), in two unrelated patients.Conclusion
Our data showed a lower number of collagen OI pathogenic variants in Vietnamese patients compared to reported rates for Asian populations. The OI mutational profile of the Vietnamese population is unique and related to the presence of a high number of recessive mutations in non-collagenous OI genes. Further analysis of OI patients negative for collagen mutations, is required.5.
I. M. Khidiyatova I. A. Skachkova E. V. Saifullina R. V. Magzhanov O. A. Schagina R. A. Zinchenko A. N. Petrin E. K. Khusnutdinova 《Russian Journal of Genetics》2013,49(7):771-777
Hereditary motor and sensory neuropathy (HMSN) type IIA is caused by mutations in the mitofusin type-2 (MFN2) gene and represents one of the most common axonal forms of HMSN. We determined the spectrum and frequency of MFN2 gene mutations in patients from the Bashkortostan Republic (BR). Four different mutations were revealed in 5 out of 170 unrelated patients, i.e., c.2113G>A (p.Val705Ile) (1.2% among all types of HMSN in the total sample of patients and 2% among patients of Tatar ethnicity). This mutation was described previously; c.775C>T (p.Arg259Cys) (0.6%, in the total sample of patients and 2% among the patients of Tatar ethnicity); c.776G>A (p.Arg259His) (0.6% in the total sample of patients and 1.5% among the patients of Russians ethnicity); and c.2171T>C (p.Leu724Pro) (1.2% in the total sample of patients and 7.4% among the patients of Bashkirs ethnicity). These are new mutations that were not observed among healthy family members and in control samples of healthy subjects. Five identified nucleotide substitutions represent single nucleotide polymorphisms of the gene, including c.892G>A (p.Gly298Arg), c.957C>T (Gly319Gly), and c1039-222t>c, which were described previously, while c.175+28c>t and c.2204+15t>c represent new nucleotide substitutions in the intron regions of the gene. 相似文献
6.
Chartier-Harlin MC Dachsel JC Vilariño-Güell C Lincoln SJ Leprêtre F Hulihan MM Kachergus J Milnerwood AJ Tapia L Song MS Le Rhun E Mutez E Larvor L Duflot A Vanbesien-Mailliot C Kreisler A Ross OA Nishioka K Soto-Ortolaza AI Cobb SA Melrose HL Behrouz B Keeling BH Bacon JA Hentati E Williams L Yanagiya A Sonenberg N Lockhart PJ Zubair AC Uitti RJ Aasly JO Krygowska-Wajs A Opala G Wszolek ZK Frigerio R Maraganore DM Gosal D Lynch T Hutchinson M Bentivoglio AR Valente EM Nichols WC Pankratz N 《American journal of human genetics》2011,(3):140-406
Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease. 相似文献
7.
Reis FC Alexandrino F Steiner CE Norato DY Cavalcanti DP Sartorato EL 《Journal of applied genetics》2005,46(1):105-108
Osteogenesis imperfecta (OI) is a genetic disorder of increased bone fragility and low bone mass. Severity varies widely, ranging from intrauterine fractures and perinatal lethality to very mild forms without fractures. Most patients with a clinical diagnosis of OI have a mutation in the COL1A1 or COL1A2 genes that encode the a chains of type I procollagen, the major protein in bones. Hence, the aim of the present study was to identify mutations in the COL1A1 gene in 13 unrelated Brazilian OI patients. This is the first molecular study of OI in Brazil. We found 6 mutations, 4 of them novel (c.1885delG, p.P239A, p.G592S, p.G649D) and 2 previously described (p.R237X and p.G382S). Thus, the findings show that there are no prevalent mutations in our sample, and that their distribution is similar to that reported by other authors, with preponderance of substitutions for glycine in the triple helix domain, causing OI types II, III and IV. 相似文献
8.
I. M. Khidiyatova E. G. Bagautdinova D. V. Galieva N. B. Krupina O. A. Shchagina T. B. Tiburkova R. V. Magzhanov A. V. Polyakov E. K. Khusnutdinova 《Russian Journal of Genetics》2008,44(10):1201-1207
Hereditary motor and sensory neuropathy type 1X (HMSN 1X) is the second most frequent form of demyelinating polyneuropathies and is caused by mutations in the gene for connexin 32 protein (Cx32, GJB1). The contribution of HMSN 1X to the structure of HMSN in the Republic of Bashkortostan was determined. The GJB1 mutations were detected in 18 out of 131 unrelated patients, which constituted 13.7%. The four missense mutations identified were represented by: p.Pro87Ala (c.259C > G) with the frequency of 10%; p.Arg22Gln (c.65G > A) (2.98%); p.Arg15Gln (c.44G > A); and p.Thr86Ile (c.257C > T) (0.8%). The latter mutation was never described before. The frequent mutation p.Pro87Ala was tested for linkage disequilibrium with the alleles of five polymorphic microsatellite DNA loci associated with the GJB1. It was demonstrated that 10 out of 13 chromosomes carrying the mutation mentioned had common DXS8111-DXS983-DXS8107-DXS8052 haplotype. This finding suggested the distribution of this mutation on the territory of the Republic of Bashkortostan as a result of the founder effect. The mutational spectrum of GJB1 and mutation frequencies observed in the HMSN 1X patients examined were characterized by ethnic heterogeneity. This finding will provide development of most optimal algorithm of the HMSN DNA diagnostics in the region. 相似文献
9.
Bliznets EA Galkina VA Matiushchenko GN Kisina AG Markova TG Poliakov AV 《Genetika》2012,48(1):112-124
Search for mutations in the connexin 26 gene (GJB2) is a routine molecular-genetic analysis ofthe hereditary deafness worldwide. However, till now there is no assessment of the diagnostic significance of this analysis for Russian patients, and there are difficulties in interpretation of the results of DNA diagnostics. In the present study, a sample of 705 patients with nonsyndromic autosomal recessive deafness from different regions of Russian Federation was investigated. A portion of deafness like DFNB1 caused by mutations in the GJB2 gene among the sample was 46%. The frequency of deafness of such genetic type was 1:1000, that is, the frequency of isolated autosomal recessive deafness was 1:500 in the population. It was found that each sixteenth individual in Russia is a heterozygous carrier of the mutation in the GJB2gene. Totally, 20 pathological GJB2 alleles were detected; among them, a c.35delG mutation with the allelic frequency 81% prevails. Six most frequent mutations (c.35delG, c.313_326de114, c.-23+1G>A (IVS1+1G>A), c.235delC, c.167delT, and p.Glul20del), which account for 95% of pathological GJB2 alleles, were detected. Mutations previously not described in the GJB2 gene (c.129delG, p.Gly200Arg, and c[Arg127His, Gly160Ser]) were found. An optimal algorithm of molecular investigation of Russian patients which detects up to 100% of mutations in the GJB2 gene was suggested. Data concerning a clinical significance of p.Met34Thr and p.Va137Ile mutations are confirmed in the study. Eight polymorphic substitutions in the GJB2gene which do not have clinical significance (p.Va127Ile, c.*3C>A, p.Va115311e, p.Gly160Ser, c.Arg127His, p.Glull4Gly (c.341A>G), c.-45C>A, and p.Ala149Thr) were also detected. 相似文献
10.
Background
Osteogenesis imperfecta (OI) is a rare bone disorder. In 90% of cases, OI is caused by mutations in the COL1A1/2 genes, which code procollagen α1 and α2 chains. The main aim of the current research was to identify the mutational spectrum of COL1A1/2 genes in Estonian patients. The small population size of Estonia provides a unique chance to explore the collagen I mutational profile of 100% of OI families in the country.Methods
We performed mutational analysis of peripheral blood gDNA of 30 unrelated Estonian OI patients using Sanger sequencing of COL1A1 and COL1A2 genes, including all intron-exon junctions and 5′UTR and 3′UTR regions, to identify causative OI mutations.Results
We identified COL1A1/2 mutations in 86.67% of patients (26/30). 76.92% of discovered mutations were located in the COL1A1 (n = 20) and 23.08% in the COL1A2 (n = 6) gene. Half of the COL1A1/2 mutations appeared to be novel. The percentage of quantitative COL1A1/2 mutations was 69.23%. Glycine substitution with serine was the most prevalent among missense mutations. All qualitative mutations were situated in the chain domain of pro-α1/2 chains.Conclusion
Our study shows that among the Estonian OI population, the range of collagen I mutations is quite high, which agrees with other described OI cohorts of Northern Europe. The Estonian OI cohort differs due to the high number of quantitative variants and simple missense variants, which are mostly Gly to Ser substitutions and do not extend the chain domain of COL1A1/2 products.11.
Conte C Gambardella S Bulli C Rinaldi F Di Marino D Falconi M Bramanti P Desideri A Novelli G 《Genetic testing》2008,12(3):437-442
Mutations within EDA1 gene, which encodes for the ectodysplasin, cause X-linked anhidrotic ectodermal dysplasia. In this study, 23 Italian patients with anhidrotic ectodermal dysplasia were analyzed for mutations in EDA1 gene. We set up a rapid protocol through denaturing high-performance liquid chromatography, followed by sequencing, that allowed the characterization of 18 mutations, 14 novel and 4 recurrent: 8 missense mutations (p.L51Q, p.H54R, p.R156H twice, p.C332F, p.D316H, p.T378M, and p.A349T), 3 in-frame deletions (p.G82_P84del, p.A179_P191del, and p.L354del), 1 gross deletion (p.G168_G265del, identified through direct sequencing and PCR), 4 altered splicing (c.949-13T > C, c.741 + 1G/T, c.793 + 4A > T, and c.924 + 1G/T), 1 nonsense (p.Y3X), and 1 synonymous mutation (c.741G > A). Moreover, structural analysis of three missense mutations shows that alteration of the electrostatic surface of the protein (p.D316N), the break of intermonomer interactions (p.A349T) and destabilization of the single monomer structure (p.T378M), may irreversibly invalidate the EDA-A1 binding properties. Our data confirm and extend the large spectrum of EDA1 mutations and provide a rapid and efficient molecular protocol for testing EDA1 mutations in EDA patients. 相似文献
12.
E. A. Bliznetz V. A. Galkina G. N. Matyushchenko A. G. Kisina T. G. Markova A. V. Polyakov 《Russian Journal of Genetics》2012,48(1):101-112
Molecular testing for mutations in the connexin 26 gene (GJB2) is a routine diagnostic analysis for subjects with hereditary hearing loss worldwide. However, till now there is no assessment
of the diagnostic significance of this analysis for Russian patients, and there are difficulties in interpretation of the
results of DNA diagnostics. In the present study, a sample of 705 patients with nonsyndromic autosomal recessive hearing loss
from different regions of Russian Federation was investigated. A portion of DFNB1 hearing loss caused by mutations in the
GJB2 gene among the sample was 46%. The frequency of DFNB1 hearing loss was 1:1000, that is, the frequency of isolated autosomal
recessive hearing loss 1:500 in the population. It was found that each sixteenth individual in Russia is a heterozygous carrier
of the mutation in the GJB2 gene. Totally, 20 pathological GJB2 alleles were detected; among them, a c.35delG mutation with the allelic frequency 81% prevails. Six most frequent mutations
(c.35delG, c.313_326del14, c.23+1G>A (IVS1+1G>A), c.235delC, c.167delT, and p.Glu120del), which account for 95% of pathological
GJB2 alleles, were detected. Mutations previously not described in the GJB2 gene (c.129delG, p.Gly200Arg, and c[Arg127His, Gly160Ser]) were found. An optimal algorithm of molecular testing of Russian
patients which detects up to 100% of mutations in the GJB2 gene was suggested. Data concerning a clinical significance of p.Met34Thr and p.Val37Ile mutations are confirmed in the study.
Eight polymorphic substitutions in the GJB2 gene which do not have clinical significance (p.Val27Ile, c.*3C>A, p.Val153Ile, p.Gly160Ser, c.Arg127His, p.Glu114Gly (c.341A>G),
c.-45C>A, and p.Ala149Thr) were also detected. 相似文献
13.
Xiran Wang Yu Pei Jingtao Dou Juming Lu Jian Li Zhaohui Lv 《Genetics and molecular biology》2015,38(1):1-7
Osteogenesis imperfecta (OI) is a family of genetic disorders associated with bone
loss and fragility. Mutations associated with OI have been found in genes encoding
the type I collagen chains. People with OI type I often produce insufficient α1-chain
type I collagen because of frameshift, nonsense, or splice site mutations in
COL1A1 or COL1A2. This report is of a Chinese
daughter and mother who had both experienced two bone fractures. Because skeletal
fragility is predominantly inherited, we focused on identifying mutations in
COL1A1 and COL1A2 genes. A novel mutation in
COL1A1, c.700delG, was detected by genomic DNA sequencing in the
mother and daughter, but not in their relatives. The identification of this mutation
led to the conclusion that they were affected by mild OI type I. Open reading frame
analysis indicated that this frameshift mutation would truncate α1-chain type I
collagen at residue p263 (p.E234KfsX264), while the wild-type protein would contain
1,464 residues. The clinical data were consistent with the patients’ diagnosis of
mild OI type I caused by haploinsufficiency of α1-chain type I collagen. Combined
with previous reports, identification of the novel mutation
COL1A1-c.700delG in these patients suggests that
additional genetic and environmental factors may influence the severity of OI. 相似文献
14.
Peiran Zhou Yi Liu Fang Lv Min Nie Yan Jiang Ou Wang Weibo Xia Xiaoping Xing Mei Li 《PloS one》2014,9(9)
Bruck syndrome (BS) is an extremely rare form of osteogenesis imperfecta characterized by congenital joint contracture, multiple fractures and short stature. We described the phenotypes of BS in two Chinese patients for the first time. The novel compound heterozygous mutations c.764_772dupACGTCCTCC (p.255_257dupHisValLeu) in exon 5 and c.1405G>T (p.Gly469X) in exon 9 of FKBP10 were identified in one proband. The novel compound heterozygous mutations c.1624delT (p.Tyr542Thrfs*18) in exon 14 and c.1880T>C (p.Val627Ala) in exon 17 of PLOD2 were identified in another probrand. Intravenous zoledronate was a potent agent for these patients, confirmed the efficacy of bisphosphonates on this disease. In conclusion, the novel causative mutations identified in the patients expand the genotypic spectrum of BS. 相似文献
15.
16.
Sang-Joo Kim Hong-Joon Park Borum Sagong Seung-Hyun Bae Se-Kyung Oh Jeong-In Baek Jae Young Choi Kyu-Yup Lee Un-Kyung Kim 《Genes & genomics.》2016,38(10):961-966
The collagen type XI alpha 2 gene (COL11A2) is associated with autosomal dominant non-syndromic hearing loss (ADNSHL), and all mutations of this gene in ADNSHL are missense mutations. To evaluate its potential as a major causative gene of ADNSHL in the Korean population, we performed genetic analysis of COL11A2 in 75 unrelated Korean patients with ADNSHL. Consequently, 5 non-synonymous variants, 7 synonymous variants, and 6 intronic variants were identified in COL11A2. Among them, a novel variant, p.G829R (c.2485G>C) was found in a patient as a heterozygote. However, pedigree analysis showed this variation was not co-segregated with hearing loss. Previously reported variants p.G230W (c.688G>T) and p.P1422L (c.4265C>T) were discovered in Korean patients. However, these variants were also detected in normal individuals. These results suggest that COL11A2 is not a major causative gene of ADNSHL in the Korean population. 相似文献
17.
Chen J Ma Z Jiao X Fariss R Kantorow WL Kantorow M Pras E Frydman M Pras E Riazuddin S Riazuddin SA Hejtmancik JF 《American journal of human genetics》2011,88(6):2255-838
Congenital cataracts (CCs), responsible for about one-third of blindness in infants, are a major cause of vision loss in children worldwide. Autosomal-recessive congenital cataracts (arCC) form a clinically diverse and genetically heterogeneous group of disorders of the crystalline lens. To identify the genetic cause of arCC in consanguineous Pakistani families, we performed genome-wide linkage analysis and fine mapping and identified linkage to 3p21-p22 with a summed LOD score of 33.42. Mutations in the gene encoding FYVE and coiled-coil domain containing 1 (FYCO1), a PI(3)P-binding protein family member that is associated with the exterior of autophagosomes and mediates microtubule plus-end-directed vesicle transport, were identified in 12 Pakistani families and one Arab Israeli family in which arCC had previously been mapped to the overlapping CATC2 region. Nine different mutations were identified, including c.3755 delC (p.Ala1252AspfsX71), c.3858_3862dupGGAAT (p.Leu1288TrpfsX37), c.1045 C>T (p.Gln349X), c.2206C>T (p.Gln736X), c.2761C>T (p.Arg921X), c.2830C>T (p.Arg944X), c.3150+1 G>T, c.4127T>C (p.Leu1376Pro), and c.1546C>T (p.Gln516X). Fyco1 is expressed in the mouse embryonic and adult lens and peaks at P12d. Expressed mutant proteins p.Leu1288TrpfsX37 and p.Gln736X are truncated on immunoblots. Wild-type and p.L1376P FYCO1, the only missense mutant identified, migrate at the expected molecular mass. Both wild-type and p. Leu1376Pro FYCO1 proteins expressed in human lens epithelial cells partially colocalize to microtubules and are found adjacent to Golgi, but they primarily colocalize to autophagosomes. Thus, FYCO1 is involved in lens development and transparency in humans, and mutations in this gene are one of the most common causes of arCC in the Pakistani population. 相似文献
18.
Witecka J Auguściak-Duma AM Kruczek A Szydło A Lesiak M Krzak M Pietrzyk JJ Männikkö M Sieroń AL 《Journal of applied genetics》2008,49(3):283-295
Osteogenesis imperfecta (OI) is a bone dysplasia caused by mutations in theCOL1A1 andCOL1A2 genes. Although the condition has been intensely studied for over 25 years and recently over 800 novel mutations have been
published, the relation between the location of mutations and clinical manifestation is poorly understood. Here we report
missense mutations inCOL1A1 of several OI patients. Two novel mutations were found in the D1 period. One caused a substitution of glycine 200 by valine
at the N-terminus of D1 in OI type I/IV, lowering collagen stability by 50% at 34°C. The other one was a substitution of valine
349 by phenylalanine at the C-terminus of D1 in OI type I, lowering collagen stability at 37.5°C. Two other mutations, reported
before, changed amino residues in D4. One was a lethal substitution changing glycine 866 to serine in genetically identical
twins with OI type II. That mutated amino acid was near the border of D3 and D4. The second mutation changed glycine 1040
to serine located at the border of D4 and D0.4, in a proband manifesting OI type III, and lowered collagen stability at 39°C
(2°C lower than normal). Our results confirm the hypothesis on a critical role of the D1 and D4 regions in stabilization of
the collagen triple-helix. The defect in D1 seemed to produce a milder clinical type of OI, whereas the defect in the C-terminal
end of collagen type caused the more severe or lethal types of OI. 相似文献
19.
Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis 总被引:1,自引:0,他引:1
Jordan CT Cao L Roberson ED Duan S Helms CA Nair RP Duffin KC Stuart PE Goldgar D Hayashi G Olfson EH Feng BJ Pullinger CR Kane JP Wise CA Goldbach-Mansky R Lowes MA Peddle L Chandran V Liao W Rahman P Krueger GG Gladman D Elder JT Menter A Bowcock AM 《American journal of human genetics》2012,90(5):796-808
20.
Campbell BG Wootton JA MacLeod JN Minor RR 《Archives of biochemistry and biophysics》2000,384(1):37-46
The sequence of canine COL1A1 cDNA was determined from four overlapping COL1A1 RT-PCR products generated from canine fibroblast RNA. In the translated region, nucleotide identity between canine and human COL1A1 cDNA was 93.2%, although the canine sequence lacked nucleotides 204 to 215 in the region coding for the N-propeptide. Amino acid identity was 97.7%. Total RNA and type I collagen were collected from cultured skin fibroblasts of a 12-week-old male golden retriever with pathologic fractures suggestive of osteogenesis imperfecta (OI) and dentinogenesis imperfecta. Sequential, overlapping approximately 1,000-bp fragments of COL1A1 and COL1A2 cDNA were each amplified by RT-PCR using primers containing 5' T7 polymerase sites. These PCR products were transcribed with T7 RNA polymerase, hybridized into RNA duplexes, and cleaved at mismatch sites with RNase. The proband had an unique cleavage pattern for the fragment of COL1A1 mRNA spanning nucleotides 709 to 1,531. Sequence analysis identified a G to C point mutation for nucleotide 1,276, predicting a codon change from glycine (GGA) to alanine (GCA) for amino acid 208. This change disrupts the normal Gly-X-Y pattern of the collagen triple helix. Restriction enzyme digestion of the RT-PCR product was consistent with a heterozygous COL1A1 mutation. Type I collagen was labeled with 3H-proline, salt precipitated, and analyzed by SDS-PAGE. Pepsin digested alpha chains were over-hydroxylated, and procollagen processing was delayed. Thus, canine and human OI appear homologous in terms of clinical presentation, etiology, and pathogenesis. 相似文献