摘要目的:筛查并分析南京地区黏多糖贮积症（mucopolysaccharidosis，MPS）相关基因的致病性和可疑致病性位点在新生儿群体中的携带情况。方法:回顾性选择2022年3月至2024年10月于南京医科大学附属妇产医院出生并采用芯片捕获二代测序技术检测MPS相关基因的新生儿为研究对象，总结新生儿MPS相关基因的致病性和可疑致病性变异的携带情况。结果:共纳入30 043名新生儿，检出1例男性新生儿MPSⅡ编码的杜糖醛酸-2-硫酸酯酶（iduronate 2-sulfatase，IDS）基因存在p.Arg273Trp可疑致病性变异，其干血斑IDS活性0.1 nmol/（h·μl），低于截断值，诊断为MPSⅡ潜在患儿，MPSⅡ患病率为1/30 043（0.003%）。此外还检出319例MPS其他分型相关基因变异的携带者，包括MPSⅠ携带者70例（0.233%）、MPSⅢA携带者44例（0.146%）、MPSⅢB携带者52例（0.173%）、MPSⅢC携带者41例（0.136%）、MPSⅣA携带者23例（0.077%）、MPSⅣB携带者56例（0.186%）、MPSⅥ携带者22例（0.073%）、MPSⅦ携带者11例（0.037%）。其中MPSⅠ变异频率较高的位点依次为p.Leu346Arg（0.025%）、p.Ser633Leu（0.013%）；MPSⅢA变异频率较高的位点依次为p.Asp235Asn（0.023%）、p.Arg377Cys（0.008%）；MPSⅢB变异频率较高的位点依次为p.Trp361Arg（0.007%）、p.Tyr335Cys（0.007%）、p.Tyr309Cys（0.007%）；MPSⅢC变异频率较高的位点依次为c.493+1G>A（0.023%）、p.Arg344Cys（0.012%）、c.1250+1G>A（0.007%）；MPSⅣB变异频率较高的位点依次为p.Asp448Val（0.020%）、p.Arg49Cys（0.008%）；MPSⅥ变异频率较高的位点依次为p.Gly303Glu（0.007%）。结论:本文共检测出1例MPSⅡ潜在患儿，MPSⅡ患病率为1/30 043；319例MPS其他分型的携带者，携带率最高分型依次为MPSⅠ、MPS ⅣB和MPSⅢB。

abstractsObjective:To screen and analyze the pathogenicity and suspected pathogenic loci in mucopolysaccharidosis (MPS)-associated genes among neonates in Nanjing.Methods:From March 2022 to October 2024, neonates born in our hospital and received chip capture next-generation sequencing for MPS-associated genes were retrospectively studied. The pathogenicity and suspected pathogenic loci were summarized.Results:A total of 30 043 neonates were included. One male neonate was identified with a likely pathogenic variant p.Arg273Trp in iduronate 2-sulfatase (IDS) gene for MPSⅡ and dried blood spot showed below-cutoff IDS activity 0.1 nmol/(h·μl). This neonate was a suspected MPSⅡ patient, yielding an MPSⅡ prevalence of 1/30 043 (0.003%). Additionally, 319 carriers of genetic variants associated with other MPS subtypes were identified, including 70 MPSⅠ carriers (0.233%), 44 MPSⅢA carriers (0.146%), 52 MPSⅢB carriers (0.173%), 41 MPSⅢC carriers (0.136%), 23 MPSⅣA carriers (0.077%), 56 MPSⅣB carriers (0.186%), 22 MPSⅥ carriers (0.073%) and 11 MPSⅦ carriers (0.037%). The loci with higher mutation frequencies for MPSⅠ were p.Leu346Arg (0.025%) and p.Ser633Leu (0.013%). For MPSⅢA, p.Asp235Asn (0.023%) and p.Arg377Cys (0.008%). For MPSⅢB, p.Trp361Arg (0.007%), p.Tyr335Cys (0.007%) and p.Tyr309Cys (0.007%). For MPSⅢC, c.493+1G>A (0.023%), p.Arg344Cys (0.012%) and c.1250+1G>A (0.007%). For MPSⅣB, p.Asp448Val (0.020%) and p.Arg49Cys (0.008%). For MPSⅥ, p.Gly303Glu(0.007%).Conclusions:This study identifies 1 suspected MPSⅡ case, yielding an MPSⅡ prevalence of 1/30 043. Among 319 carriers of other MPS subtypes, MPSⅠ, MPSⅣB and MPSⅢB show higher carrier rates.