Wen Wei, Yin Dan, Huang Fangfang, Guo Meng, Tian Tian, Zhu Hui, Yang Yun
Neonatal Screening Centre, Shenzhen Maternity and Child Healthcare Hospital, No. 3012, Fuqiang Road, Futian District, Shenzhen, Guangdong Province, China.
BGI-Wuhan, Wuhan, 430075, China.
BMC Med Genet. 2016 Feb 3;17:9. doi: 10.1186/s12881-016-0273-7.
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.
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.
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.
精氨琥珀酸尿症（ASAuria；OMIM 207900）是一种罕见的常染色体隐性遗传性尿素循环障碍疾病，可导致血液和尿液中精氨琥珀酸积聚。我们旨在对该患者进行基因检测，以帮助临床医生准确诊断。
在本研究中，我们使用新一代测序（NGS）和外显子捕获技术对家庭成员进行分析。我们在中国汉族ASAuria患者中鉴定出精氨琥珀酸裂解酶（ASL）基因的复合杂合突变。外显子捕获显示，第5外显子中的c.434A>G（p.(D145G)）突变导致形成了一个缺失第5外显子的替代转录本。c.1366C>T（p.(R456W)）突变先前已在一名意大利患者中报道。
这是首次报道错义突变导致替代剪接，进而导致ASAuria患者第5外显子缺失。本研究还证明了NGS在ASAuria家系突变鉴定和分子诊断中的价值。
