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1.
We have characterized the mutations in 1050 carriers of the β-thalassemia gene and analyzed their regional distribution in
India. The majority of β-thalassemia carriers were migrants from Pakistan and their pattern of mutations differed from the
rest. The frequency of the 619-bp deletion was 33.3% among the migrants from Pakistan, 8–17% in the northern states, and less
than 5% in the other states. Among non-migrant subjects, the predominant mutation was IVS-I-5 (G→C), varying from 85% in the
southern states and 66–70% in the eastern states to 47–60% in the northern states. The mutation IVS-I-1 (G→T) was observed
at high frequency among the migrants from Pakistan (26.2%), but with very low/ zero frequency in the other states. Mutations
at codons 8/9 (+G) and codons 41/42 (–CTTT) were distributed in all regions of India with a frequency varying from 3% to 15%.
Only eight of 12 published rare mutations were observed in subjects from different parts of India. Mutations of codon 5 (–CT)
and codons 47/48 (+ATCT) were found exclusively in migrants from Pakistan, and mutation –88 (C→T) was detected only in subjects
from Punjab, Haryana, and Uttar Pradesh. Using the amplification refractory mutation system technique, mutations were successfully
identified in 98.2% of subjects. Overall, 91.8% of the subjects had one of the five commonest mutations [IVS-I-5 (G→C), 34.1%;
619-bp deletion, 21.0%; IVS-I-1 (G→T) 15.8%; codons 8/9 (+G), 12.1%, and codons 41/42 (–CTTT), 8.7%], 5.9% of the subjects
had a less common mutation, while 1.8% of the carriers remained uncharacterized. The application of this knowledge has helped
to successfully establish a program of genetic counselling and prenatal diagnosis of β-thalassemia in order to reduce the
burden of this disease in India.
Received: 15 October 1996 / Accepted: 18 February 1997 相似文献
2.
N. El-Hashemite Mary Petrou A. S. Khalifa N. M. Heshmat Magdy S. Rady Joy D. A. Delhanty 《Human genetics》1997,99(2):271-274
β-thalassaemia is a major health problem in Egypt. It has been estimated that of the 1.5 million live births, 1000 children
with β-thalassaemia major are born annually. Although the available treatment has increased the life expectancy of patients,
it is still unsatisfactory and represents a significant drain on the country’s resources. National screening and prenatal
diagnosis programmes can be provided in Egypt once the spectrum of β-thalassaemia mutations has been identified within the
Egyptian population. We have examined 16 DNA samples with 21 β-thalassaemia mutations that remained unidentified in a study
of 54 patients reported by Rady and colleagues in 1996. Using the polymerase chain reaction and single strand conformation
analysis we identified the following changes: frameshift (FS) codon (CD) 8/9 (+G), 4 FS CD 29 (–G) and 2 novel mutations in
exon I (15 CD 22 A-C and 1 FS CD 28 –C). In addition, a silent, probably polymorphic mutation, CD 17 G-A was present in all
chromosomes.
Received: 19 August 1996 / Revised: 21 September 1996 相似文献
3.
Alma R. Villalobos-Arámbula Rocío Bustos Maricela Casas-Castañeda Esperanza Gutiérrez Francisco J. Perea Swee L. Thein B. Ibarra 《Human genetics》1997,99(4):498-500
β-globin haplotypes of 20 β-thalassemia (β-thal) and 87 βA Mexican mestizo chromosomes were analyzed to ascertain the origin of the β-thal alleles and the frequencies and distribution
of the βA haplotypes among northwestern Mexican mestizos. Sixteen β-thal chromosomes carried six Mediterranean alleles [five codon
39 C→T; two IVS1:1 G→A; two IVS1:5 G→A; three IVS1:110 G(A; one codon 11 (–T) and three (δβ)°-thal]; the remaining four were
linked to three rare alleles (two –28 A→C and one each: –87 C→T and initiation codon ATG→GTG). Among the 87 βA chromosomes, 17 different 5′ haplotypes with frequencies for 1, 3, 2 and 5 of 39.0%, 17. 2%, 9.2% and 6.9%, respectively,
were observed. The β-haplotype analysis showed that 13 out of 16 Mediterranean chromosomes could easily be explained by gene
migration; however, one codon 39 associated with haplotype 4 (– – – – + + –), one IVS1:1 with haplotype 1(+ – – – – + +) and
one IVS1:5 G→A, may represent separate mutational events. Analysis of the rare alleles showed that the –28 A→C mutation was
associated with the commonest βA haplotype in Mexican mestizos, Mediterraneans and the total world population; therefore an independent origin cannot be ruled
out. The –87 C→T and initiation codon ATG→GTG were found with β-haplotypes different from the reported ones, suggesting an
indigenous origin.
Received: 23 April 1996 / Revised: 10 September 1996 相似文献
4.
Beta Thalassemia has been reported to be a common genetic disorder in Iran. To establish the molecular spectrum of the beta
thalassemias in the Kermanshah Province of Iran, 185 unrelated beta thalassemia patients with Kurdish ethnic background were
studied (181 β-thalassemia major and 4 β-thalassemia intermedia). Using polymerase chain reaction-amplification refractory
mutation system (PCR-ARMS), restriction fragment length polymorphism (RFLP) and direct genomic sequencing twenty different
mutations were identified accounting for 98.1% of the alleles. Approximately 80.8% of β-thalassemia chromosomes had β0 mutation. The most prevalent mutation was the IVSII-1 (G→A) (32.97%), followed by CD8/9 +G (13.51%), IVSI-110 (C→T) (8.38%),
CD 36/37 −T (7.84%), CD8 −AA (5.94%), CD15 (G→A) (4.86%) and IVSI-1 (G→A) (4.59%). All of these mutations accounted for 78.1%
of the alleles. The results described here will be of valuable help in the development of successful prevention programs for
the population of Kermanshah. 相似文献
5.
G. P. Patrinos Panagoula Kollia Aphrodite Loutradi-Anagnostou Dimitris Loukopoulos Manoussos N. Papadakis 《Human genetics》1998,102(6):629-634
We report a new type of non-deletional hereditary persistence of fetal hemoglobin that is due to a C→T transition at position
–158, relative to the Cap site of the human Aγ-globin gene. This mutation was identified in three unrelated adult cases presenting slightly elevated levels of fetal hemoglobin
(Hb F), i.e. 2.9–5.1%, and normal hematological indices. Our sequencing results, from both polymerase chain reaction-amplified
and subcloned DNA fragments, indicate that the Aγ–158C→T mutation occurred by two independent gene conversion events in the three cases studied. In addition, hematological
and molecular data, including restriction fragment length polymorphism haplotyping in the β-globin gene cluster, extended haplotype analysis inside the γ-globin gene region and routine analysis of three tandem repeat loci (D1S80, 3′-HVR/apoB and F8vWf), led us to conclude that
the Aγ–158C→T mutation in one of the three cases occurred recently in the parental germ line (P=99.47%), representing the first example of a de novo gene conversion event identified in humans.
Received: 10 November 1997 / Accepted: 10 February 1998 相似文献
6.
Kakavas VK Konstantinos KV Plageras P Panagiotis P Vlachos TA Antonios VT Papaioannou A Agelos P Noulas VA Argiris NV 《Molecular biotechnology》2008,38(2):155-163
Single strand conformation polymorphism (SSCP) is a reproducible, rapid and quite simple method for the detection of deletions/insertions/rearrangements
in polymerase chain reaction amplified DNA. All the details for the use of PCR–SSCP are presented in the direction of genetic
diseases (β-thalassaemia, cystic fibrosis), optimum gel conditions, sensitivity and the latest modifications of the method,
which are applied in most laboratories. This non-radioactive PCR–SSCP method can be reliably used to identify mutations in
patients (β-globin, CFTR), provided suitable controls are available. Moreover, it is widely used for mutation identification
in carriers (β-thalassaemia, cystic fibrosis), making it particularly useful in population screening. 相似文献
7.
Soudani A Hadjfredj S Zribi M Messaadi F Messaoud T Masmoudi A Zribi M Fendri C 《Journal of microbiology (Seoul, Korea)》2011,49(3):413-417
Forty three isoniazid (INH)-resistant Mycobacterium tuberculosis isolates were characterized on the basis of the most common INH associated mutations, katG315 and mabA −15C→T, and phenotypic properties (i.e. MIC of INH, resistance associated pattern, and catalase activity). Typing for resistance
mutations was performed by Multiplex Allele-Specific PCR and sequencing reaction. Mutations at either codon were detected
in 67.5% of isolates: katG315 in 37.2, mabA −15C→T in 27.9 and both of them in 2.4%, respectively. katG sequencing showed a G insertion at codon 325 detected in 2 strains and leading to amino acid change T326D which has not been
previously reported. Distribution of each mutation, among the investigated strains, showed that katG S315T was associated with multiple-drug profile, high-level INH resistance and loss or decreased catalase activity; whereas
the mabA −15C→T was more prevalent in mono-INH resistant isolates, but it was not only associated with a low-level INH resistance.
It seems that determination of catalase activity aids in the detection of isolates for which MICs are high and could, in conjunction
with molecular methods, provide rapid detection of most clinical INH-resistant strains. 相似文献
8.
9.
W. E. Rodriguez Romero M. Castillo M. A. Chaves G. F. Saenz L.-H. Gu J. B. Wilson E. Baysal N. S. Smetanina J. Y. Leonova T. H. J. Huisman 《Human genetics》1996,97(6):829-833
We have identified a minor hemoglobin component (∼5%) in the blood of a healthy Costa Rican female, but not in her mother
and two brothers (father not studied), that has an His→Arg replacement at position β77 (Hb Costa Rica). No other amino acid
replacements were observed and no β- or γ-chain-like peptides were present. Hb Costa Rica has a normal stability. Sequence
analyses of numerous polymerase chain reaction (PCR)-amplified segments of DNA that contain exon 2 of the β gene failed to
identify a CAC→CGC (His→Arg) mutation. The same was the case when cDNA was sequenced, indicating that a β-Costa Rica-mRNA could not be detected
with this procedure. Gene mapping of genomic DNA with BglII, BamHI, and HindIII gave normal fragments only and with the same intensity as observed for the fragments of a normal control. The quantities
of the β chain variants Hb J-Iran and Hb Fukuyama with related mutations at β77 vary between 30% and 45% in heterozygotes,
whereas that of Hb F-Kennestone with the same His→Arg mutation but in the Gγ-globin gene, is a high 40%–45% (as percentage of total Gγ) in a heterozygous newborn. These different observations exclude a heterozygosity of the A→G mutation at codon β77, as well
as a deletion comparable to that of Hbs Lepore or Kenya, or a β-globin gene duplication, and point to a nontraditional inheritance
of Hb Costa Rica. Allele-specific amplification of cDNA with appropriate primers identified the presence of a low level of
mutated mRNA in the reticulocytes of the patient, which was confirmed by dotblot analysis of the same material with 32P-labeled probes. Comparable amplification products were not observed in genomic DNA. The A→G mutation apparently occurred
in a somatic cell at a relatively early stage in the development of the hematopoietic cell system, and Hb Costa Rica accumulated
through rapid cell divisions in patchy areas in the bone marrow (somatic mosaicism). An unequal distribution of Hb Costa Rica
over the red cells supports this possibility.
Received: 25 August 1995 / Revised: 13 December 1995 相似文献
10.
YANG Jianbo WU Lijun LI Li WU JiadaoYU Zengliang XU Zhihong 《中国科学:生命科学英文版》1997,40(1):107-112
While M13mp18 double-stranded DNA was irradiated with ion beam, and transfected intoE. coli JM103, a decrease of transfecting activity was discovered. The lacZ- mutation frequency at 20% survival could reach (3.6–16.8) × 104, about 2, 3–10 times that of unirradiated M13DNA. Altogether, 27 IacZ-mutants were selected, 10 of which were used for sequencing. 7 of the sequenced mutants show base changes in 250-bp region
examined (the remaining 3 mutants probably have base changes outside the regions sequenced). 5 of the base-changed mutants
contain more than one mutational base sites (some of them even have 5–6 mutational base sites in 250-bp region examined);
this dense distribution of base changes in polysites has seldom been seen in X-rays, Y-rays or UV induced DNA mutations. Our
experiments also showed that the types of base changes include transitions(50%), transversions (45%) and deletion (5%); no
addition or duplication was observed. The transitions were mainly C→T and A→G; the transversions were mainly C→A and C→G.
The mutations involving cytosine residue (in the template strand) constitute about 60% of all the base changes observed. In
comparison with the surrounding sequences of mutational base sites, the base located between TG and CT is found to be easily
substituted. 相似文献
11.
H. C. Tsou Xiao Li Ping Xiao Xun Xie Alexandra C. Gruener Hong Zhang R. Nini Karen Swisshelm Virginia Sybert Terry M. Diamond Rebecca Sutphen M. Peacocke 《Human genetics》1998,102(4):467-473
Cowden’s syndrome (CS) is an autosomal dominant disorder associated with an increased risk of developing benign and malignant
tumors in a variety of tissues, including the skin, thyroid, breast and brain. Women with CS are felt to have an increased
risk of developing breast cancer, and virtually all women with CS develop bilateral fibrocystic disease of the breast. Recently,
a series of germline mutations have been identified from CS families in a gene known as PTEN/MMAC1/TEP1. In this study, we
used heteroduplex analysis and direct sequencing analysis and identified three novel germline mutations in the PTEN/MMAC1/TEP1
coding sequence from unrelated individuals with CS. We report a de novo transition (T→C) at nucleotide 335 in exon 5. This
missense mutation resulted in a leucine to proline (CTA to CCA) change at codon 112. We also describe a novel splice site
mutation (801+2T→G) in intron 7 that caused exon skipping in PTEN/MMAC1/TEP1 mRNA. The third mutation we report is a missense
mutation, consisting of a transition (T→C) at nucleotide 202 in exon 3, resulting in a tyrosine to histidine (TAC to CAC)
change at codon 68. Finally, we also detected a rare polymorphism in exon 7 of the PTEN/MMAC1/TEP1 coding sequence. These
data confirm the observation that mutations of the PTEN/MMAC1/ TEP1 coding sequence are responsible for at least some cases
of CS, and further define the spectrum of mutations in this autosomal dominant disorder.
Received: 21 October 1997 / Accepted: 15 December 1997 相似文献
12.
13.
Mutations in the exon 10 of prolactin receptor gene change the egg production performance in Wanjiang white goose 总被引:1,自引:0,他引:1
To select the molecular genetic markers related to egg performance of Wanjiang white goose, prolactin receptor gene (PRLR)
was adopted to be a candidate gene in our study. Five pairs of primers (P1–P5) were designed to detect the SNPs of PRLR gene
by PCR-SSCP method. The results revealed that polymorphisms were discovered in the PCR products amplified with P4 primers
in PRLR exon 10, three genotypes were found: AA, AB and AC. The sequence of AB genotype is the same as original sequence (DQ660982)
in NCBI. There are five mutations in AA genotype: C → A at 840 bp, C → T at 862 bp, T → C at 875 bp, T → A at 963 bp, A → T
at 989 bp, resulting in amino acid mutations: His → Asn, Thr → Ile, Asn → Lys, Thr → Ser, and synonymous mutation at 875 bp.
Sequencing revealed five mutations in AC genotype: G → T at 816 bp, A → T at 861 bp, C → T at 862 bp, T → C at 875 bp, A → G
at 948 bp, causing amino acid mutations of Val → Phe, Thr → Phe, synonymous mutations at 875 and 963 bp. Besides, there are
an N-glycosylation site (NQSR), three casein kinase II phosphorylation sites including SIIE, SKTE, and SLMD in AA genotype; three
casein kinase II phosphorylation sites including SIIE, SKTE, and TLMD in AB genotype; three casein kinase II phosphorylation
sites including SIFE, SKTE, and TLMD in AC genotype. The annual egg yielding of AB genotype geese are significantly more than
those of AA and AC genotype geese on the average (P < 0.05). It is suggested for the first time that PRLR is a promising candidate gene that can affect egg performance in Wanjiang
white goose. 相似文献
14.
The antisense fragments, which were available inin vitro system, were cloned into the mammalian expression vector pcDNA3, and were transfected into H654 cells, a mammalian cell line
stably expressing the thalassaemic (IVS-2-654 C→T) human β-globin gene. In these transfected cells, the level of correctly
spliced β-globin mRNA in total β-globin mRNA (β/(β + β*)) was improved from 0.07 (0 d) to 0.22 (3 d), and this effect persisted
for up to 15 d post transfection. All the results demonstrated that antisense RNAs were able to be transcribed from the antisense
fragment expression vectors stably and effectively suppressed aberrant splicing pattern of the mutated β-globin gene (IVS-2-654
C→T) and restored correct splicing pathway. This work provided a novel approach with potential clinical significance to gene
therapy of this kind of splicing mutants including β-thalassaemia (IVS-2-654 C→T) by antisense RNAs.
Project supported in part by the National Natural Science Foundation of China (Grant Nos. 39780019, 39392903) and the Shanghai
Life Sciences Research Centre. 相似文献
15.
Unlike the other haemoglobinopathies, few researches have been published concerning α-thalassaemia in Tunisia. The aim of
the present work is to acquire further data concerning α-thalassaemia prevalence and molecular defects spectrum in Tunisia,
by collecting and studying several kinds of samples carrying α-thalassaemia. The first survey conducted on 529 cord blood
samples using cellulose acetate electrophoresis, have displayed the prevalence of 7.38% Hb Bart’s carriers at birth. Molecular
analyses were conducted by PCR and DNA sequencing on 20 families’ cases from the above survey carrying the Hb Bart’s at birth
and on 10 Hb H diseased patients. The results showed six α-globin gene molecular defects and were responsible for α-thalassaemia:
-α3.7, - -MedI, αTSaudi, α2cd23GAG→Stop, Hb Greone Hart: α1119CCT→TCT corresponding to 11 genotypes out of which two are responsible for Hb H disease (- -Med/-α3.7) and (αTSaudiα/αTSaudiα) and a newly described polymorphism: α+6C→G. The geographical repartition of α-thal carriers showed that the -α3.7 deletion is distributed all over the country, respectively the αHphI and αTSaudi seem to be more frequent in the central region of the northeast region. The haematological and clinical data showed a moderate
phenotype with a late age of diagnosis for Hb H disease. This work had permitted, in addition to an overview on α-thalassaemia
in the country, the optimization of protocols for α-thalassaemia detection in our lab, allowing further investigations concerning
phenotype-genotype correlation in sickle cell disease or β-thalassaemia. 相似文献
16.
Maria Manuela M. Caniça Chang Y. Lu Rajagopal Krishnamoorthy Gérard C. Paul 《Journal of molecular evolution》1997,44(1):57-65
The molecular diversity of inhibitor-resistant TEM (IRT) enzymes was explored using a strategy which involved DNA amplification
by polymerase chain reaction (PCR), analysis of restriction fragment length polymorphism (RFLP), and direct nucleotide sequencing.
The study of plasmid-borne genes from 27 strains, resistant to amoxicillin and β-lactamase-inhibitor combinations, identified
mutations resulting in amino acid change at positions 69, 244, 275, and 276 known to be associated with the IRT phenotype
and a mutation at nucleotide position 162 in the promoter region. These mutations were found to lie on two different gene
sequences, described here as ``TEM-1B like' and ``TEM-2 like' restriction linkage groups. Further analysis, of nucleotide
sequences of promoter and coding regions of the β-lactamases, confirmed that a given mutation causing IRT phenotype could
be associated with two different gene sequence frameworks and two different causal mutations could lie on identical gene sequence
framework. These data argue in favor of convergent phenotypic evolution of IRT enzymes under the selective pressure imposed
by the intensive clinical use of β-lactam–β-lactamase inhibitor combinations.
Received: 18 March 1996 / Accepted: 15 July 1996 相似文献
17.
Maria Tzetis E. Kanavakis Thalia Antoniadi Stavros Doudounakis George Adam Christos Kattamis 《Human genetics》1996,99(1):121-125
To completely characterize the spectrum of mutations in the cystic fibrosis transmembrane conductance regulator gene in Greek
cystic fibrosis (CF) patients, we screened 500 CF chromosomes by denaturing gradient gel electrophoresis followed by direct
sequencing. We identified 48 mutations, accounting for 85.6% of CF chromosomes. They included eight novel mutations, three
of which we have described before and five (E822X, Y247X, 2752–26A→G, 3152delT, and 2751+T→A), which are described in this
report. The detection of such a high proportion of Greek CF mutations is important for improving prenatal and genetic diagnosis
of CF in Greece.
Received: 10 May 1996 相似文献
18.
Zhang H Zheng X Ji T Fu L Bai D Liao Y Zhang H Ding Y Zheng L 《Cell biochemistry and biophysics》2012,62(3):415-420
We determined frequency/types of K-ras mutations in colorectal/lung cancer. ADx-K-ras kit (real-time/double-loop probe PCR)
was used to detect somatic tumor gene mutations compared with Sanger DNA sequencing using 583 colorectal and 244 lung cancer
paraffin-embedded clinical samples. Genomic DNA was used in both methods; mutation rates at codons 12/13 and frequency of
each mutation were detected and compared. The data show that 91.4% colorectal and 59.0% lung carcinoma samples were detected
conclusively by DNA sequencing, whereas 100% colorectal and lung samples were detected by ADx-K-ras kit. K-ras gene mutations
were detected in 32.9–27.4% colorectal samples using kit and sequencing methods, respectively. Whereas 10.6–8.3% lung cancer
samples were positively detected by kit and sequencing methods, respectively. Notably, 172/677 showed mutations and 467/677
showed wild type by both methods; 38 samples showed mutations with kit but wild type with sequencing. Mutations in colorectal
samples were as follows: GGT → GAT/codon-12 (35.1%); GGC → GAC/codon-13 (26.6%); GGT → GTT/codon-12 (18.2%); and GGT → GCT/codon-12
(1.6%). Mutations in lung samples were as follows: GGT > GTT/codon-12 (40.9%) and GGT > GCT/codon-12 (4.5%). In conclusion,
K-ras mutations involved 32.2% colorectal and 10.6% lung samples among this cohort. ADx-K-ras real-time PCR showed higher
detection rates (P < 0.05). The kit method has good clinical applicability as it is simple, fast, less prone to contamination and hence can
be used effectively and reliably for clinical screening of somatic tumor gene mutations. 相似文献
19.
Autosomal recessive polycystic kidney disease (ARPKD) is a rare hereditary renal cystic disease involving multiple organs, mainly the kidney and liver. Parents who had an affected child with ARPKD are in strong demand for an early and reliable prenatal diagnosis to guide the future pregnancies. Here we provide an example of prenatal diagnosis of an ARPKD family where traditional antenatal ultrasound examinations failed to produce conclusive results till 26th week of gestation. Compound heterozygous mutations c.274C>T (p.Arg92Trp) and c.9059T>C (p.Leu3020Pro) were identified using targeted exome sequencing in the patient and confirmed by Sanger sequencing. Further, the mother and father were revealed to be carriers of heterozygous c.274C>T and c.9059T>C mutations, respectively. Molecular prenatal diagnosis was performed for the current pregnancy by direct sequencing plus linkage analysis. Two mutations identified in the patient were both found in the fetus. In conclusion, compound heterozygous PKHD1 mutations were elucidated to be the molecular basis of the patient with ARPKD. The newly identified c.9059T>C mutation in the patient expands mutation spectrum in PKHD1 gene. For those ultrasound failed to provide clear diagnosis, we propose the new prenatal diagnosis procedure: first, screening underlying mutations in PKHD1 gene in the proband by targeted exome sequencing; then detecting causative mutations by direct sequencing in the fetal DNA and confirming results by linkage analysis. 相似文献
20.
Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency 总被引:14,自引:0,他引:14
Van Kuilenburg AB Vreken P Abeling NG Bakker HD Meinsma R Van Lenthe H De Abreu RA Smeitink JA Kayserili H Apak MY Christensen E Holopainen I Pulkki K Riva D Botteon G Holme E Tulinius M Kleijer WJ Beemer FA Duran M Niezen-Koning KE Smit GP Jakobs C Smit LM Van Gennip AH 《Human genetics》1999,104(1):1-9
Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterised by thymine-uraciluria in
homozygous deficient patients and has been associated with a variable clinical phenotype. In order to understand the genetic
and phenotypic basis for DPD deficiency, we have reviewed 17 families presenting 22 patients with complete deficiency of DPD.
In this group of patients, 7 different mutations have been identified, including 2 deletions [295–298delTCAT, 1897delC], 1
splice-site mutation [IVS14+1G>A)] and 4 missense mutations (85T>C, 703C>T, 2658G>A, 2983G>T). Analysis of the prevalence
of the various mutations among DPD patients has shown that the G→A point mutation in the invariant splice donor site is by
far the most common (52%), whereas the other six mutations are less frequently observed. A large phenotypic variability has
been observed, with convulsive disorders, motor retardation and mental retardation being the most abundant manifestations.
A clear correlation between the genotype and phenotype has not been established. An altered β-alanine, uracil and thymine
homeostasis might underlie the various clinical abnormalities encountered in patients with DPD deficiency.
Received: 25 August 1998 / Accepted: 24 November 1998 相似文献