Identification of citrullinaemia carrier and detection of a new silent mutation at 240bp position in ASS1 gene of normal Holstein cattle (original) (raw)
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Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia
PubMed, 1994
Citrullinemia is an autosomal recessive disease caused by a genetic deficiency of argininosuccinate synthetase. In order to characterize mutations in Japanese patients with classical citrullinemia, RNA isolated from 10 unrelated patients was reverse-transcribed, and cDNA amplified by PCR was cloned and sequenced. The 10 mutations identified included 6 missense mutations (A118T, A192V, R272C, G280R, R304W, and R363L), 2 mutations associated with an absence of an exon 7 or exon 13, 1 mutation with a deletion of the first 7 bp in exon 16 (which might be caused by abnormal splicing), and 1 mutation with an insertion of 37 bp within exons 15 and 16 in cDNA. The insertion mutation and the five missense mutations (R304W being excluded) are new mutations described in the present paper. These are in addition to 14 mutations (9 missense mutations, 4 mutations associated with an absence of an exon in mRNA, and 1 splicing mutation) that we identified previously in mainly American patients with neonatal citrullinemia. Two of these 20 mutations, a deletion of exon 13 sequence and a 7-bp deletion in exon 16, were common to Japanese and American populations from different ethnic backgrounds; however, other mutations were unique to each population. Furthermore, the presence of a frequent mutation--the exon 7 deletion mutation in mRNA, which accounts for 10 of 23 affected alleles--was demonstrated in Japanese citrullinemia. This differs from the situation in the United States, where there was far greater heterogeneity of mutations.
International Journal of Molecular Biology, 2018
Background: Citrullinemia type 1 is an inherited autosomal recessive disease and a member of Urea Cycle Disorders (UCD), 1 characterized by accumulation of ammonia in the blood as a result of defect in enzyme called "argininosuccinate synthetase" (ASAS), which is responsible for converting citrulline to arginine. Signs and symptoms appear after birth, if untreated CTLN1 may progress to coma or death. Purpose: To Screen ASS1 gene in two Saudi families with citrullinemia disorder (one affected family and the other is a carrier) from AL-Madinah AL-Monawarah. Define mutations may help in treatment and cure progress for patients. Methods: Genetic analysis using sequencing technology was carried out to detect mutations in ASS1 gene. Results: Two Mutations were detected. First family affected and unaffected members (III:3, II:2) have a homozygous missense variant in exon 7 (c.501 C>T, p.166 His>His). While in second family affected member (III:1) has a homozygous splice site mutation in exon 5 (c.364-2 A>G) and unaffected member (II:2) has a heterozygous mutation in exon 5 (c.371 A>T) of ASS1 gene. Conclusion: Missense and splice site mutations were found in both affected and carrier members, homozygous and heterozygous respectively. The splice site region is important because mutations in these areas may lead to entire exon being spliced out of the mRNA. A heterozygous mutation makes individual a carrier of the disease. Research Objectives A. Main objective: To Screen ASS1 Gene in Two Saudi Families with Citrullinemia Disorder in AL-Madinah AL-Monawarah B. Specific objectives: To screen ASS1 gene in Saudi families by ABI 3500 genetic analyzer. To compare ASS1 sequence in affected individuals and his/her unaffected family members.
Argininosuccinate synthetase deficiency: mutation analysis in 3 Thai patients.
2005
Remarkable improvements in public health, nutrition, hygiene, and availability of medical services in the last 20 years have significantly reduced infant and childhood mortality in Thailand. Therefore, many rare and previously unidentified genetic disorders, which, in the past, usually led to the death of affected infants before a definitive diagnosis, have now been increasingly recognized. Recently, we identified three unrelated patients from Thailand who suffered from citrullinemia, one of five inherited types of urea cycle disorders.
Mutations and Polymorphisms in the HumanArgininosuccinate Lyase(ASL) Gene
Human Mutation, 2013
Citrullinemia type I is an autosomal recessive disorder that is caused by a deficiency of the urea cycle enzyme argininosuccinate synthetase (ASS1). Deficiency of ASS1 shows various clinical manifestations encompassing severely affected patients with fatal neonatal hyperammonemia as well as asymptomatic individuals with only a biochemical phenotype. This is a comprehensive report of all 87 mutations found to date in the ASS1 gene on chromosome 9q34.1. A large proportion of the mutations (n 5 27) are described here for the first time. Mutations are distributed throughout exons 3 to 15, most of them being identified in exons 5, 12, 13, and 14. The mutation G390R in exon 15 is the single most common mutation in patients with the classical phenotype. Certain mutations clearly link to specific clinical courses but the clinical phenotype cannot be anticipated in all patients. This update presents a survey of the correlation between mutations in the ASS1 gene and the respective clinical courses as described so far. It also sheds light on the geographic incidence of the mutations. Enzymatic studies have been done in bacterial and human cell systems. However, the prognostic value of genetic aberrations with respect to their effect on protein function and clinical manifestation remains uncertain.
A search for the primary abnormality in adult-onset type II citrullinemia
American journal of human genetics, 1993
Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, we show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia. We also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients h...
Acta Veterinaria Scandinavica, 2010
Background: Bovine leukocyte adhesion deficiency (BLAD), deficiency of uridine monophosphate synthase (DUMPS), complex vertebral malformation (CVM), bovine citrullinaemia (BC) and factor XI deficiency (FXID) are autosomal recessive hereditary disorders, which have had significant economic impact on dairy cattle breeding worldwide. In this study, 350 Holstein cows reared in Turkey were screened for BLAD, DUMPS, CVM, BC and FXID genotypes to obtain an indication on the importance of these defects in Turkish Holsteins. Methods: Genomic DNA was obtained from blood and the amplicons of BLAD, DUMPS, CVM, BC and FXID were obtained by using PCR. PCR products were digested with TaqI, AvaI and AvaII restriction enzymes for BLAD, DUMPS, and BC, respectively. These digested products and PCR product of FXID were analyzed by agarose gel electrophoresis stained with ethidium bromide. CVM genotypes were detected by DNA sequencing. Additionally, all genotypes were confirmed by DNA sequencing to determine whether there was a mutant allele or not. Results: Fourteen BLAD, twelve CVM and four FXID carriers were found among the 350 Holstein cows examined, while carriers of DUMPS and BC were not detected. The mutant allele frequencies were calculated as 0.02, 0.017, and 0.006 for BLAD, CVM and FXID, respectively with corresponding carrier prevalence of 4.0% (BLAD), 3.4% (CVM) and 1.2% (FXID). Conclusion: This study demonstrates that carriers of BLAD, CVM and FXID are present in the Turkish Holstein population, although at a low frequency. The actual number of clinical cases is unknown, but sporadic cases may appear. As artificial insemination is widely used in dairy cattle breeding, carriers of BLAD, CVM and FXID are likely present within the population of breeding sires. It is recommended to screen breeding sires for these defective genes in order to avoid an unwanted spread within the population.