Whole-Exome Sequencing Identified a Novel Compound Heterozygous Genotype in ASL in a Chinese Han Patient with Argininosuccinate Lyase Deficiency

الملخص EN

Pathogenic variants in the argininosuccinate lyase (ASL) gene have been shown to cause argininosuccinate lyase deficiency (ASLD); therefore, sequencing analysis offers advantages for prenatal testing and counseling in families afflicted with this condition.

Here, we performed a genetic analysis of an ASLD patient and his family with an aim to offer available information for clinical diagnosis.

The research subjects were a 23-month-old patient with a high plasma level of citrulline and his unaffected parents.

Whole-exome sequencing identified potential related ASL gene mutations in this trio.

Enzymatic activity was detected spectrophotometrically by a coupled assay using arginase and measuring urea production.

We identified a novel nonsynonymous mutation (c.206A>G, p.Lys69Arg) and a stop mutation (c.637C>T, p.Arg213∗) in ASL in a Chinese Han patient with ASLD.

The enzymatic activity of a p.Lys69Arg ASL construct in human embryonic kidney 293T cells was significantly reduced compared to that of the wild-type construct, and no significant activity was observed for the p.Arg213∗ construct.

Compound heterozygous p.Lys69Arg and p.Arg213∗ mutations that resulted in reduced ASL enzyme activity were found in a patient with ASLD.

This finding expands the clinical spectrum of ASL pathogenic variants.