Kurpinski Kyle T, Magyari Patricia A, Gorlin Robert J, Ng David, Biesecker Leslie G
Genetic Diseases Research Branch, National Human Genome Research Institute/NIH, Building 49 Room 4C72, Bethesda, MD 20892-4472, USA.
Am J Med Genet A. 2003 Jul 1;120A(1):1-4. doi: 10.1002/ajmg.a.10201.
The Robin sequence is a well-known cause of cleft palate and can be sporadic or familial, isolated or syndromic. We present a four-generation family with a lethal disorder inherited in an X-linked recessive pattern that includes Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistence of the left superior vena cava. We have designated this disorder "TARP" syndrome. All affected males die in infancy of unknown causes. An X-chromosome linkage scan was performed using 14 unaffected members of a single large family and 40 STRP markers. The gene was mapped to an 11-cM region in Xp11.23-q13.3. Markers DXS1003 and DXS8092 flank the region and three-point linkage analyses revealed a maximum LOD score of 2.75 at marker DXS1039. We have designated this locus as TARP. This locus was mapped without genotyping any affecteds and demonstrates that rare, lethal disorders can be evaluated by genetic linkage, even when no affected probands are available for study.
罗宾序列征是腭裂的一个常见病因，可为散发性或家族性，孤立性或综合征性。我们报告一个四代家族，其患有以X连锁隐性模式遗传的致死性疾病，包括马蹄内翻足、房间隔缺损、罗宾序列征和左上腔静脉永存。我们将这种疾病命名为“TARP”综合征。所有受影响的男性均在婴儿期不明原因死亡。使用一个大家庭中的14名未受影响成员和40个STRP标记进行了X染色体连锁扫描。该基因被定位到Xp11.23-q13.3的一个11厘摩区域。标记DXS1003和DXS8092位于该区域两侧，三点连锁分析显示在标记DXS1039处最大LOD值为2.75。我们将这个位点命名为TARP。该位点在未对任何患者进行基因分型的情况下被定位，表明即使没有受影响的先证者可供研究，罕见的致死性疾病也可通过遗传连锁分析进行评估。
