儿童Gitelman综合征的SLC12A3基因复杂杂合突变
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摘要
目的儿童Gitelman综合征(Gitelman Syndrome,GS)是一种由编码肾脏远曲小管钠-氯协同转运蛋白(Na-Cl cotransporter,NCCT)的SLC12A3基因突变引起的疾病。文中旨在探讨基因突变在鉴别诊断儿童GS中的意义。方法收集2例诊断为GS的儿童,采用一代测序法及多重连接探针扩增技术(multiplex ligation-dependent probe amplification,MPLA)对基因突变位点进行研究。结果 2例患儿基因检测发现1例男性患儿存在SLC12A3基因的复杂杂合突变即c.1964G>A,p.(Arg655His)联合8号外显子缺失突变;1例女性患儿存在SLC12A3基因的2个杂合突变即c.2543A>T,p.(Asp848Val)和c.976del G,p.(Val326fs)突变;其中8号外显子缺失突变和c.2543A>T,p.(Asp848Val)突变为发现的新突变位点。结论基因诊断是重要确诊手段,儿科医师需要提高认识,以防漏诊及误诊。
Objective Gitelman Syndrome is a disease caused by the mutation of Na-Cl cotransporter gene( SLC12A3). The article studied the significance of diagnosis and identification by genetic mutation. Methods We collected the clinical data,then we sequenced the SLC12A3 gene by the first sequencing technology and MLPA. Results SLC12A3 complicated heterozygotic mutation was observed. One of them showed c. 1964 G > A,p.( Arg655His) and exon 8 deletion mutation,the other showed c. 2543 A > T,p.( Asp848Val) and c. 976 del G,p.( Val326fs) mutation of SLC12A3 gene in children. Conclusion The final diagnosis depended on gene diagnosis. Pediatrician must recognize the manifestations to advoid misdiagnosis.
Objective Gitelman Syndrome is a disease caused by the mutation of Na-Cl cotransporter gene( SLC12A3). The article studied the significance of diagnosis and identification by genetic mutation. Methods We collected the clinical data,then we sequenced the SLC12A3 gene by the first sequencing technology and MLPA. Results SLC12A3 complicated heterozygotic mutation was observed. One of them showed c. 1964 G > A,p.( Arg655His) and exon 8 deletion mutation,the other showed c. 2543 A > T,p.( Asp848Val) and c. 976 del G,p.( Val326fs) mutation of SLC12A3 gene in children. Conclusion The final diagnosis depended on gene diagnosis. Pediatrician must recognize the manifestations to advoid misdiagnosis.
引文
[1]Gaur A,Ambey R,Gaur BK.Gitelman's syndrome:Rare presentation with growth retardation[J].Indian J Nephrol,2014,24(1):60-62.
[2]Sampathkumar K,Muralidharan U,Kannan A,et al.Childhood bartter's syndrome:an Indian case series[J].Indian J Nephrol,2010,20(4):207-210.
[3]Mhasde DR,Gautam S,Zore RR,et al.Gitelman's syndrome[J].J Assoc Physicians India,2009,57(3):211-212.
[4]Sundar U,Lakkas Y,Asole D,et al.Gitelman's syndrome presenting as recurrent paralytic ileus due to chronic renal tubular K+wasting[J].J Assoc Physicians India,2010,58(5):322-324.
[5]Gitelman HJ,Graham JB,Welt LG.A new familial disorder characterized by hypokalemia and hypomagnesemia[J].Trans Assoc Am Physicians,1966,79(1):221-235.
[6]Glaudemans B,Yntema HG,San-Cristobal P,et al.Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome[J].Eur J Hum Genet,2012,20(3):263-270.
[7]Balavoine AS,Bataille P,Vanhille P,et al.Phenotype-genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome[J].Eur J Endocrinol,2011,165(4):665-673.
[8]Vargas-Poussou R,Dahan K,Kahila D,et al.Spectrum of mutations in Gitelman syndrome[J].J Am Soc Nephrol,2011,22(4):693-703.
[9]Gamba G.Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters[J].Physiol Rev,2005,85(2):423-493.
[10]Singh PJ,Nash JL,Santella RN,et al.Gitelman's syndrome:report of a 19-year old woman with intractable hypomagnesemia and hypokalemia and a review ofthe syndrome[J].S D J Med,1999,52(10):377-380.
[11]Jiang L,Chen C,Yuan T,et al.Clinical severity of gitelman syndrome determined by serum magnesium[J].Am J Nephrol,2014,39(4):357-366.
[2]Sampathkumar K,Muralidharan U,Kannan A,et al.Childhood bartter's syndrome:an Indian case series[J].Indian J Nephrol,2010,20(4):207-210.
[3]Mhasde DR,Gautam S,Zore RR,et al.Gitelman's syndrome[J].J Assoc Physicians India,2009,57(3):211-212.
[4]Sundar U,Lakkas Y,Asole D,et al.Gitelman's syndrome presenting as recurrent paralytic ileus due to chronic renal tubular K+wasting[J].J Assoc Physicians India,2010,58(5):322-324.
[5]Gitelman HJ,Graham JB,Welt LG.A new familial disorder characterized by hypokalemia and hypomagnesemia[J].Trans Assoc Am Physicians,1966,79(1):221-235.
[6]Glaudemans B,Yntema HG,San-Cristobal P,et al.Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome[J].Eur J Hum Genet,2012,20(3):263-270.
[7]Balavoine AS,Bataille P,Vanhille P,et al.Phenotype-genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome[J].Eur J Endocrinol,2011,165(4):665-673.
[8]Vargas-Poussou R,Dahan K,Kahila D,et al.Spectrum of mutations in Gitelman syndrome[J].J Am Soc Nephrol,2011,22(4):693-703.
[9]Gamba G.Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters[J].Physiol Rev,2005,85(2):423-493.
[10]Singh PJ,Nash JL,Santella RN,et al.Gitelman's syndrome:report of a 19-year old woman with intractable hypomagnesemia and hypokalemia and a review ofthe syndrome[J].S D J Med,1999,52(10):377-380.
[11]Jiang L,Chen C,Yuan T,et al.Clinical severity of gitelman syndrome determined by serum magnesium[J].Am J Nephrol,2014,39(4):357-366.