CAJ | 학술논문

目的描述Ⅲ型原发性高草酸尿症(PHⅢ)1例患儿的临床特征并对该家系进行致病基因突变分析研究.方法通过直接测序法对该家系可疑突变基因AGXT、GRHPR和HOGA1进行直接测序分析.以100例健康人作为对照.结果患儿发病早(0.8岁),临床表现以肾结石和梗阻性肾病为主,但肾钙质沉着症表现轻微.实验室检查发现患儿有显著的高草酸尿、高钙尿和低枸橼酸尿.HOGA1基因分析发现2个新的杂合突变(复合杂合),一是位于6号外显子最后l位和6号内含子第1位连续2个bp的突变(c.834_834+1GG＞ TT);另一个是位于6号外显子最后l位碱基鸟嘌呤突变为腺嘌呤(c.834G＞A).这2个突变很可能导致剪切突变.100例非相关的健康人未发现存在相同突变.另外,该患儿还携带1个单核苷酸多态性(SNP) (c.715G＞A,p.V239I).其他2个候选基因AGXT和GRHPR未发现可疑突变.结论新发现2个剪切突变位点与PHⅢ有关.这是亚洲首次报道PHⅢ患者及其突变基因分析.
목적 묘술Ⅲ형원발성고초산뇨증(PHⅢ)1례환인적림상특정병대해가계진행치병기인돌변분석연구.방법 통과직접측서법대해가계가의돌변기인AGXT、GRHPR화HOGA1진행직접측서분석.이100례건강인작위대조.결과 환인발병조(0.8세),림상표현이신결석화경조성신병위주,단신개질침착증표현경미.실험실검사발현환인유현저적고초산뇨、고개뇨화저구연산뇨.HOGA1기인분석발현2개신적잡합돌변(복합잡합),일시위우6호외현자최후l위화6호내함자제1위련속2개bp적돌변(c.834_834+1GG＞ TT);령일개시위우6호외현자최후l위감기조표령돌변위선표령(c.834G＞A).저2개돌변흔가능도치전절돌변.100례비상관적건강인미발현존재상동돌변.령외,해환인환휴대1개단핵감산다태성(SNP) (c.715G＞A,p.V239I).기타2개후선기인AGXT화GRHPR미발현가의돌변.결론 신발현2개전절돌변위점여PHⅢ유관.저시아주수차보도PHⅢ환자급기돌변기인분석.
Objective To describe the clinical characteristics of one child with primary hyperoxaluria types Ⅲ, and to analyze the potential mutant genes in his family.Methods AGXT, GRHPR and HOGA1 genes were analyzed by direct sequencing analysis in this family.One hundred unrelated healthy subjects were also analyzed as controls.Results The child had early onset of symptoms (0.8 year).His principal clinical manifestation included nephrolithiasis and obstructive nephropathy, however his nephrocalcinosis was mild.And he presented high urine oxalate, high urine calcium, and lower citrate levels.Two novel heterozygous mutations in HOGA1 were identified (compound heterozygous), one mutation was a 2-bp substitution at the last position in exon 6 and the first position of intron 6 respectively (c.834_834 + 1GG ＞ TT);another was a guanine to adenine substitution of the last nucleotide of exon 6 (c.834G ＞ A).Both of these variants found in this study probably acted as splicing mutations.Direct sequencing analysis failed to find these mutations in 100 unrelated healthy subjects.In addition, a SNP (c.715G ＞ A, p.V239I) was found in this family.There were no mutations detected in AGXT and GRHPR.Conclusions Two novel mutations are identified probably in association with PH Ⅲ.This is the first description and investigation on mutant gene analysis of PHⅢ in Asia.