CAJ | 학술논문

目的：本文报道家族性青少年高尿酸血症肾病（FJHN）一家系的尿调节素（UMOD）编码基因新的位点突变并结合文献复习，以期引起肾脏病学者对该病的足够重视。方法收集、核实和整理分析1例 FJHN 先证者的临床特征、实验室检查及该家系其他成员相关的临床资料；检测先证者及其长子和外甥的 UMOD 编码基因外显子2～5变异情况。结果先证者呈现典型的 FJHN 临床表现，包括青年发病，显著性高尿酸血症、痛风性关节炎和痛风石，早期即有夜尿增多等尿浓缩功能减退的表现，肾功能损害持续缓慢进展，至40岁左右时发展为终末期肾病。家系调查及基因突变检测显示，家系三代中至少有高尿酸血症12人，其中3人已死于尿毒症，先证者也已进入尿毒症期，并正在接受血液透析治疗。先证者及其长子经基因检测均有相同的基因突变：UMOD 编码基因位第4外显子上第854碱基出现 C ／A 嵌合子（正常参考基因碱基为 C）变异，使氨基酸序列第285位丙氨酸（A， GCG）变异为谷氨酸（E，GAG）。无高尿酸血症的先证者外甥经基因检测未发现基因外显子2～5变异。结论家族性青少年高尿酸血症肾病可能与 UMOD 编码基因位第4外显子上第854碱基变异（此为一新发现的基因突变）有关，对有显著高尿酸血症、痛风，尤其是有慢性肾脏病家族史的青（少）壮年患者，应考虑有无 FJHN 的可能性，通过医学影像学、肾活检和（或）UMOD 基因的检测，尽早明确诊断、避免误诊、漏诊。
목적：본문보도가족성청소년고뇨산혈증신병（FJHN）일가계적뇨조절소（UMOD）편마기인신적위점돌변병결합문헌복습，이기인기신장병학자대해병적족구중시。방법수집、핵실화정리분석1례 FJHN 선증자적림상특정、실험실검사급해가계기타성원상관적림상자료；검측선증자급기장자화외생적 UMOD 편마기인외현자2～5변이정황。결과선증자정현전형적 FJHN 림상표현，포괄청년발병，현저성고뇨산혈증、통풍성관절염화통풍석，조기즉유야뇨증다등뇨농축공능감퇴적표현，신공능손해지속완만진전，지40세좌우시발전위종말기신병。가계조사급기인돌변검측현시，가계삼대중지소유고뇨산혈증12인，기중3인이사우뇨독증，선증자야이진입뇨독증기，병정재접수혈액투석치료。선증자급기장자경기인검측균유상동적기인돌변：UMOD 편마기인위제4외현자상제854감기출현 C ／A 감합자（정상삼고기인감기위 C）변이，사안기산서렬제285위병안산（A， GCG）변이위곡안산（E，GAG）。무고뇨산혈증적선증자외생경기인검측미발현기인외현자2～5변이。결론가족성청소년고뇨산혈증신병가능여 UMOD 편마기인위제4외현자상제854감기변이（차위일신발현적기인돌변）유관，대유현저고뇨산혈증、통풍，우기시유만성신장병가족사적청（소）장년환자，응고필유무 FJHN 적가능성，통과의학영상학、신활검화（혹）UMOD 기인적검측，진조명학진단、피면오진、루진。
[Abstract ] Objective To draw enough attention from nephrologists to familial juvenile hyperuricemic nephropathy (FJHN),this paper reported a case with FJHN presented by a novel mutation of uromodulin (UMOD)gene from the proband,his oldest son,and his nephew,together with literature review.Methods Clinical manifestations and laboratory data of the proband were collected and analyzed. Mutations of exon 2-5 of UMOD-encoding gene of proband,his eldest son,and nephew were measured. Meanwhile,clinical relevant data of other members of the family were collected,validated,and analyzed. Results The proband presented with typical clinical features of FJHN,including juvenile onset,obvious hyperuricemia,gout arthritis,gout stone,early increased nocturia and other manifestations indicating decrease of urinary concentration function,continuous and slow progression of renal function damage,and occurrence of end-stage renal disease at the age of about 40 years.Pedigree investigation showed that at least 12 members within three generations of the family suffered from hyperuricemia,3 of whom died of uremia, and the proband was also suffering from uremia and receiving hemodialysis.Gene measuring showed that the proband and his eldest son had the same genetic mutation:a novel sense heterozygous chimerical mutation at the 4th exon of UMOD-coding gene was identified in the proband and his eldest son,so that,in the amino acid sequence,the 285th alanine (A,GCG)changed to glutamic acid (E,GAG),which was a newly discovered gene mutation.His nephew without hyperuricemia had no mutation on exon 2-5.Conclusion FJHN is an autosomal dominant disorder.If an adolescent has symptoms of remarkable hyperuricemia,gout, and a family history of chronic kidney disease,FJHN should be considered,and need to be recognized through medical imaging,renal biopsy,and UMOD gene mutation test,so that early correct diagnosis of FJHN should be made and misdiagnosis be avoided.