尿黑酸尿症一家系基因诊断及分析  

Gene diagnosis and analysis of alkaptonuria in a Chinese pedigree

作　　者：杨利[1] 黄慧[2] 杨玉[1] 周斌[1] 段君凯[2] 张晓珍[2] 李红[2] 郭智彬[2] 李垠娇[2] 

机构地区：[1]江西省儿童医院内分泌遗传代谢科,南昌330006 [2]江西省儿童医院中心实验室,南昌330006

出　　处：《中华实用儿科临床杂志》2015年第8期608-610,共3页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的 探讨尿黑酸尿症的临床特征和基因突变特点.方法 收集先证者及其家系成员临床资料,尿气相色谱分析尿液,采用PCR方法对尿黑酸1,2-二氧化酶（HGD）基因所有外显子检测,确定基因突变位点,Polyphen软件预测其蛋白质功能,分析基因型与表型的关系.结果 患者临床表现仅尿液为红褐色,而无皮肤、关节及脏器改变,尿气相色谱提示尿黑酸尿症（AKU）,HGD基因检测提示该家系先证者的HGD基因第2外显子c.34A＞ C（p.N12H）及第4外显子c.240A＞ T（p.Q80H）及第12外显子c.910A ＞G（p.K304E）错义突变,先证者表型正常的母亲及姐姐发现携带第2外显子c.34A＞ C（p.N12H）错义突变,先证者表型正常的父亲发现携带第12外显子c.910A＞G（p.K304E）错义突变.蛋白质功能预测后提示2号外显子c.34A＞C（p.N12H）致病性突变位点.结论 此家系中先证者为HGD基因复合杂合子突变致病,其第2外显子c.34A＞C（p.N12H）来自于母亲,第12外显子c.910A＞ G（p.K304E）错义突变来自于父亲,其父母及姐姐均为表型正常的杂合子携带者.发现2个国际上尚未报道的新HGD基因突变（p.N12H与p.K304E）,且发病年龄最早,仅有黑尿表现.Objective To study the clinical feature and genetic mutations of alkaptonuria（AKU）.Methods One patient was diagnosed with AKU disease via gas chromatography mass spectrometry （GC/MS） in the investigated family.All exon of homogentisate 1,2 dioxygenase（HGD） gene were amplified in the family by means of polymerase chain reaction（PCR） and followed by using direct DNA sequencing and Polyphen software was used to predict protein function.Results The infant only had red-brown urine,with no skin,joints,or viscera lesion,and GC/MS suggested AKU.Two heterozygous mutations of AKU were identified c.34A 〉 C（p.N12H） in exon 2 c.240A 〉 T（p.Q80H） in exon 4 and c.910A 〉 G（p.K304E） in exon 12 from the proband.The heterozygous change c.34A 〉 C（p.N12H） in exon 2 was found in the proband＇s mother and sister with normal phenotype.The proband＇s father had the heterozygous change c.910A 〉 G（p.K304E） in exon 12.Conclusions The proband is hetero-zygous compound AKU disease patient carrying on one allele with the c.34A 〉 C（p.N12H） mutation inherited from his mother and the other allele with the c.910A 〉 G（p.K304E） from his father.The parents and his sister are heterozygous carrier with normal phenotype.The p.N12H and p.K304E mutations are novel mutations not reported around world yet,which has the earliest onset age of AKU with the only symptom of dark urine.

关 键 词：尿黑酸尿症 尿黑酸1 2-二氧化酶 基因突变 基因诊断 

分 类 号：R725.8[医药卫生—儿科]