NGS in argininosuccinic aciduria detects a mutation (D145G) which drives alternative splicing of ASL: a case report study

BMC Med Genet. 2016 Feb 3:17:9. doi: 10.1186/s12881-016-0273-7.

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.

Case presentation: 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Ammonia / blood
  • Argininosuccinate Lyase / genetics*
  • Argininosuccinic Aciduria / diagnosis
  • Argininosuccinic Aciduria / genetics*
  • Asian People / genetics
  • China
  • DNA Mutational Analysis
  • Exons
  • Genetic Testing
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant, Newborn
  • Male
  • Mutation, Missense
  • Pedigree

Substances

  • Ammonia
  • Argininosuccinate Lyase