title: NGS in argininosuccinic aciduria detects a mutation (D145G) which drives alternative splicing of ASL: a case report study.
abstract: BACKGROUND
  Argininosuccinic aciduria (ASAuria; OMIM 207900) is a rare autosomal recessive heterogeneous urea cycle disorder, which leads to the accumulation of argininosuccinic acid in the blood and urine. We aimed to perform genetic test to the patient and help clinician to diagnose precisely.
  
  
  METHODS
  In this study, we use next generation sequencing (NGS) and exon trapping to analysis the family members. We identified compound heterozygous mutations of the argininosuccinate lyase (ASL) gene in a Chinese Han ASAuria patient. The c.434A>G (p.(D145G)) mutation in exon 5 was shown by exon trapping to select for the formation of an alternative transcript deleted for exon 5. The c.1366C>T (p.(R456W)) mutation had been previously reported in an Italian patient.
  
  
  CONCLUSIONS
  This is the first report of a missense mutation driving alternative splicing which results in the loss of exon 5 in ASAuria. This study also demonstrates the value of NGS in the identification of mutations and molecular diagnosis for ASAuria families.
authors: Neonatal Screening Centre, Shenzhen Maternity and Child Healthcare Hospital, No. 3012, Fuqiang Road, Futian District, Shenzhen, Guangdong Province, China. wenwei1087@sina.com.
authors: Wei
authors: W
authors: Wen
authors: BGI-Wuhan, Wuhan, 430075, China. yindan@genomics.cn.|BGI-Shenzhen, Shenzhen, 518083, China. yindan@genomics.cn.
authors: Dan
authors: D
authors: Yin
authors: Neonatal Screening Centre, Shenzhen Maternity and Child Healthcare Hospital, No. 3012, Fuqiang Road, Futian District, Shenzhen, Guangdong Province, China. 1966079076@qq.com.
authors: Fangfang
authors: F
authors: Huang
authors: Neonatal Screening Centre, Shenzhen Maternity and Child Healthcare Hospital, No. 3012, Fuqiang Road, Futian District, Shenzhen, Guangdong Province, China. szfyxszx@163.com.
authors: Meng
authors: M
authors: Guo
authors: BGI-Wuhan, Wuhan, 430075, China. tiantian1@genomics.cn.|BGI-Shenzhen, Shenzhen, 518083, China. tiantian1@genomics.cn.
authors: Tian
authors: T
authors: Tian
authors: BGI-Wuhan, Wuhan, 430075, China. 1442353589@qq.com.|BGI-Shenzhen, Shenzhen, 518083, China. 1442353589@qq.com.
authors: Hui
authors: H
authors: Zhu
authors: BGI-Wuhan, Wuhan, 430075, China. yangyun@genomics.cn.|BGI-Shenzhen, Shenzhen, 518083, China. yangyun@genomics.cn.|Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. yangyun@genomics.cn.
authors: Yun
authors: Y
authors: Yang
mesh_terms: D017398:Alternative Splicing; D000641:Ammonia / Q000097:blood; D001123:Argininosuccinate Lyase / Q000235:genetics*; D056807:Argininosuccinic Aciduria / Q000175:diagnosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002681:China; D004252:DNA Mutational Analysis; D005091:Exons; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D000641:Ammonia; D001123:Argininosuccinate Lyase