Mulley J C, Turner A M, Gedeon A K, Berdoukas V A, Huang T H, Ledbetter D H, Grierson H, Purtilo D T
Department of Cytogenetics and Molecular Genetics, Adelaide Children's Hospital, South Australia.
Clin Genet. 1992 Aug;42(2):76-9. doi: 10.1111/j.1399-0004.1992.tb03143.x.
Chorionic Villous Biopsy (CVS) for diagnosis of XLP was undertaken at 10 weeks gestation in an obligate carrier. The fetus was found to be male by cytogenetic analysis. XLP (Xq25-q26) is closely linked to the RFLP markers DXS10, DXS37 and DXS42, but only DXS10 (distal to XLP) was informative for prenatal diagnosis in this family. RFLP analysis using this marker gave a 7% risk that the fetus was affected, based on the known recombination frequency between DXS10 and XLP. Further investigation was then undertaken to obtain a rapid and more accurate diagnosis using the three highly polymorphic PCR based markers. These were the AC repeat markers DXS424 (XL5A) and DXS425 (XL90A3) and the tetramer repeat marker within HPRT. DX425 is approximately 10 cM proximal to DXS10 and HPRT but is not known with certainty to map proximal or distal to XLP. DXS424 is proximal to DXS10 and HPRT and was inferred to be proximal to XLP on the basis of map distance from HPRT estimated by linkage analysis of data from CEPH pedigrees. This was confirmed by a recombinant in the XLP family between DXS424 and DXS425, placing DXS424 proximal to XLP. Diagnosis by linkage using DXS424 and DXS425, at least one of which is proximal to XLP, and distal markers DXS10 and HPRT, increased the accuracy of diagnosis using flanking marker analysis to greater than 99% that the fetus was unaffected. HLA DR typing of the CVS showed that the fetus was DR identical to a male sibling with XLP. HLA compatibility was confirmed at delivery by full HLA typing and MLC.(ABSTRACT TRUNCATED AT 250 WORDS)
对一名肯定携带者在妊娠10周时进行绒毛取样（CVS）以诊断X连锁淋巴增生性疾病（XLP）。通过细胞遗传学分析发现胎儿为男性。XLP（Xq25 - q26）与限制性片段长度多态性（RFLP）标记DXS10、DXS37和DXS42紧密连锁，但在这个家族中，只有DXS10（位于XLP远端）可用于产前诊断。基于DXS10与XLP之间已知的重组频率，使用该标记进行RFLP分析得出胎儿受影响的风险为7%。随后进行了进一步研究，以使用三个基于聚合酶链反应（PCR）的高度多态性标记获得快速且更准确的诊断。这些标记是AC重复标记DXS424（XL5A）和DXS425（XL90A3）以及次黄嘌呤磷酸核糖转移酶（HPRT）内的四聚体重复标记。DXS425位于DXS10和HPRT近端约10厘摩处，但不确定其相对于XLP的定位是近端还是远端。DXS424位于DXS10和HPRT近端，根据来自CEPH家系数据的连锁分析估计的与HPRT的图距，推断其位于XLP近端。XLP家族中DXS424与DXS425之间的一个重组体证实了这一点，表明DXS424位于XLP近端。使用DXS424和DXS425（其中至少一个位于XLP近端）以及远端标记DXS10和HPRT进行连锁诊断，将侧翼标记分析的诊断准确性提高到胎儿未受影响的概率大于99%。绒毛取样的人类白细胞抗原（HLA）DR分型显示胎儿的DR与患XLP的男性同胞相同。分娩时通过完整的HLA分型和混合淋巴细胞培养（MLC）证实了HLA相容性。（摘要截断于250字）
