Timms K M, Edwards F J, Belmont J W, Yates J R, Gibbs R A
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
J Med Genet. 1998 Aug;35(8):646-9. doi: 10.1136/jmg.35.8.646.
Deficiency of iduronate-2-sulphatase (IDS) results in the X linked recessive lysosomal storage disorder Hunter syndrome. Determination of carrier status in families affected by this disorder has been performed using a variety of enzymatic tests. None of these tests has proved to be 100% effective at identifying carriers. The aim of this study was to perform carrier testing in a family affected by the disorder, where testing was complicated by the fact that no surviving affected subjects were available for study. Direct dye primer sequencing of PCR products was used to identify mixed bases in an obligate carrier. Two mixed bases were observed within exon VIII. The first base change (T-->A) at nucleotide position 1150 results in a missense mutation (H342Q), while the second base change (G-->T) at nucleotide position 1151 results in a nonsense mutation (G343X). Four additional female family members were screened for the same mutation. Using this approach it is possible to provide unambiguous information about a subject's carrier status and, unlike biochemical testing, this approach will be equally effective when applied to families with the mild form of this disorder.
艾杜糖醛酸-2-硫酸酯酶（IDS）缺乏会导致X连锁隐性溶酶体贮积症——亨特综合征。受该疾病影响的家庭中，已使用多种酶学检测方法来确定携带者状态。然而，这些检测方法均未被证明在识别携带者方面能达到100%的有效性。本研究的目的是在一个受该疾病影响的家庭中进行携带者检测，由于没有存活的患病个体可供研究，使得检测变得复杂。采用PCR产物的直接染料引物测序法来鉴定一名确定的携带者中的混合碱基。在外显子VIII内观察到两个混合碱基。核苷酸位置1150处的第一个碱基变化（T→A）导致错义突变（H342Q），而核苷酸位置1151处的第二个碱基变化（G→T）导致无义突变（G343X）。对另外四名女性家庭成员进行了相同突变的筛查。使用这种方法可以提供关于个体携带者状态的明确信息，并且与生化检测不同，当应用于患有该疾病轻度形式的家庭时，这种方法同样有效。
