Clinical, laboratory data and outcomes of 17 Iranian citrullinemia type 1 patients: Identification of five novel <scp><i>ASS1</i></scp> gene mutations

Moarefian, Shirin; Zamani, Mahdi; Rahmanifar, Ali; Behnam, Babak; Zaman, Talieh

doi:10.1002/jmd2.12277

Cited by 3 publications

(3 citation statements)

References 22 publications

(149 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, the Gly324Ser mutation was associated with the acute neonatal and neonatal forms. In Iran ( 7 ), many patients with classic CTLN1 possessed mutations in ASS1 (c.1168G > A; p.Gly390Arg), which led to poor prognosis including coma or death. In China, c.1168G > A mutations have been detected in patients with mild disease.…”

Section: Discussionmentioning

confidence: 99%

“…In China, CTLN1 is considered as a rare disease, whereas in other countries such as Iran ( 7 ) where consanguineous marriages occur, the incidence of CTLN1 has greatly increased. Therefore, advocating for healthy birth and postnatal care is important for preventing hereditary diseases.…”

Section: Discussionmentioning

confidence: 99%

“…In Korea ( 6 ), the most widely distributed variation is the p.Gly324Ser mutation, which has been reported in many countries such as America and Germany but has not been reported in Japan. The c.421-2A > G mutation ( 7 ) is very common in Japan. In German patients, the p.Arg363Trp mutation is the most common mutation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Citrullinemia type I in Chinese children: Identification of two novel argininosuccinate synthetase gene mutations

Xiong

Chen²

2022

Front. Pediatr.

View full text Add to dashboard Cite

BackgroundIn this study, we evaluated the clinical characteristics, prognosis, and gene mutations of five children with citrullinemia type I (CTLN1) diagnosed in our department and identified two novel ASS1 gene mutations.MethodsWe examined the clinical characteristics, prognosis, and gene mutations of the five children through data collection, tandem mass spectrometry, and whole-exon sequencing. MutationTaster, regSNP-intron, and SWISS-MODEL were used for bioinformatic analysis to evaluate the two novel gene mutations. We analyzed differences in blood ammonia and citrulline levels based on clinical phenotypes. Finally, we reviewed the medical literature describing Chinese children with CTLN1.ResultsASS1 C773 + 6T > G and c.848 delA as well as c.952_953 del insTT and c.133G > A have not been previously reported in the Human Gene Mutation Database. Using MutationTaster and regSNP-intron, we predicted that these mutations affected protein function. The 3D structure obtained using SWISS-MODEL supported this prediction. Through comparative analysis showed that the ammonia level of the neonatal type was markedly higher than that of other types, whereas citrulline levels did not differ between groups.ConclusionWe identified two novel mutations that cause disease. The blood ammonia level of neonatal form citrullinemia was markedly higher than that of other types. The genotype-phenotype association in Chinese patients remains unclear and should be further evaluated in genetic studies of larger sample sizes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Citrullinemia type I in Chinese children: Identification of two novel argininosuccinate synthetase gene mutations

Xiong

Chen²

2022

Front. Pediatr.

View full text Add to dashboard Cite

show abstract

Prenatal diagnosis of citrullinemia type 1; seven families with c.1168G>A mutation of Argininosuccinate synthetase 1 gene in Southwest Iran: A case series

Hassanlou¹,

Abiri²,

Zeinali³

2023

IJRM

View full text Add to dashboard Cite

Background: Citrullinemia type 1 is an autosomal recessive disease resulting in ammonia accumulation in the blood, and if uncontrolled may progress to coma or death in the early months after birth. Cases presentation: 7 families from Southwest Iran having one or more children in their families or relatives, who died in the early months after birth due to citrullinemia type 1 visited for genetic counseling and prenatal diagnosis. Whole-exome sequencing was performed on peripheral blood specimens and chorionic villus samples. Sanger sequencing confirmed the genetic results. Both parents were identified as carriers for the exon 15 c.1168G>A mutation in each family. The fetus in 6 out of 7 families was homozygote for A substitution on the argininosuccinate synthetase 1 gene. Conclusion: The presence of a common mutation in the argininosuccinate synthetase 1 gene in all affected families of Southwest Iran shows a possible population cluster in this area. Key words: Argininosuccinate synthetase, Chorionic villus sampling, Point mutation.

show abstract

Visualization of argininosuccinate synthetase by in silico analysis: novel insights into citrullinemia type I disorders

Gu,

Mo,

Zhuang

et al. 2024

Front. Mol. Biosci.

View full text Add to dashboard Cite

BackgroundCitrullinemia type I disorders (CTLN1) is a genetic metabolic disease caused by argininosuccinate synthetase (ASS1) gene mutation. To date, the human genome mutation database has documented over 100 variants of the ASS1 gene. This study reported a novel deletion-insertion variant of ASS1 gene and employed various prediction tools to determine its pathogenicity.MethodsWe reported a case of early-onset CTLN1. Whole exome sequencing was conducted to identify genetic mutations. We employed various structure prediction tools to generate accurate 3D models and utilized computational biology tools to elucidate the disparities between the wild-type and mutant proteins.ResultsThe patient was characterized by severe clinical manifestations, including poor responsiveness, lethargy, convulsions, and cardiac arrest. Notably, the patient exhibited significantly elevated blood ammonia levels (655 μmol/L; normal reference: 10–30 μmol/L) and increased citrulline concentrations (936 μmol/L; normal reference: 5–25 μmol/L). Whole exome sequencing revealed a in-frame deletion-insertion mutation c.1128_1134delinsG in the ASS1 gene of unknown significance, which has not been previously reported. Our finding indicated that the C- terminal helix domain of the mutant protein structure, which was an important structure for ASS1 protein to form protein tetramers, was indeed more unstable than that of the wild-type protein structure.ConclusionThrough conducting an in silico analysis on this unique in-frame deletion-insertion variant of ASS1, our aim was to enhance understanding regarding its structure-function relationship as well as unraveling the molecular mechanism underlying CTLN1.

show abstract

Clinical, laboratory data and outcomes of 17 Iranian citrullinemia type 1 patients: Identification of five novel ASS1 gene mutations

Cited by 3 publications

References 22 publications

Citrullinemia type I in Chinese children: Identification of two novel argininosuccinate synthetase gene mutations

Citrullinemia type I in Chinese children: Identification of two novel argininosuccinate synthetase gene mutations

Prenatal diagnosis of citrullinemia type 1; seven families with c.1168G>A mutation of Argininosuccinate synthetase 1 gene in Southwest Iran: A case series

Visualization of argininosuccinate synthetase by in silico analysis: novel insights into citrullinemia type I disorders

Contact Info

Product

Resources

About