The SLC22A5 genetic analysis in Chinese patients with systemic primary carnitine deficiency
10.3760/cma.j.issn.1000-6699.2017.03.007
- VernacularTitle:原发性肉碱缺乏症患者临床特点和SLC22A5基因突变分析
- Author:
Pengqiang WEN
;
Zhanling CHEN
;
Guobing WANG
;
Zhe SU
;
Lisheng WAN
;
Dong CUI
;
Gen TANG
;
Xiaohong LIU
;
Shuli CHEN
- Keywords:
Systemic primary carnitine deficiency;
SLC22A5;
Free carnitine;
Acylcarnitine;
Multiplex ligation dependent probe amplification
- From:
Chinese Journal of Endocrinology and Metabolism
2017;33(3):208-214
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the clinical and biochemical metabolic features of 12 patients with systemic primary carnitine deficiency(CDSP) and to identify the SLC22A5 gene mutation types of the disease. Method The clinical and biochemical data were collected by retrospective analysis. DNA direct sequencing and multiplex ligation dependent probe amplification(MLPA)were applied for SLC22A5 gene analysis. Result Among 12 patients with CDSP, 3 cases had evident infection factors, 6 cases with convulsions, 5 cases manifested liver hypertrophy, 8 cases with hyperammonemia, and 9 cases showed myocardial damage. All CDSP patients were detected biallelic pathogenic mutation in SLC22A5 gene by direct sequencing. The gene types include IVS2+1G>T, c.3G>T(p.Met1Ile), c.760C>T(p.Arg254X), c.1400C>G(p.Ser467Cys), c.844dupc(p.Arg282fs), c.338G>A(p.Cys113Tyr), c.51C>G(p.Phe17Leu), c.659A>T(p.Glu220Val), and c.1365dupC(p.Thr456fs). c.659A>T(p.Glu220Val) and c.1365dupC(p.Thr456fs)are novel mutations. One female patient was maternal CDSP, her child had abnormal newborn screening. The allele frequency of c.760C>T(p.Arg254X) and c.1400C>G(p.Ser467Cys) were 37.5%(9/24)and 29.2%(7/24)respectively. The MLPA test results of all patients were negative. Conclusion The clinical manifestations are complex and various in patients with CDSP. Point and small InDel(insertions/deletions)mutation constitute the major alteration in SLC22A5 gene. c.1400C>G(p.Ser467Cys) might be another prevalence mutation type in Chinese CDSP patient.
