Orenstein Susan R, Shalaby Theresa M, Finch Robert, Pfuetzer Roland H, DeVandry Suzanne, Chensny Lara J, Bannada M Michael, Whitcomb David C
Children's Hospital of Pittsburgh, Pennsylvania 15213-2583, USA.
Am J Gastroenterol. 2002 Nov;97(11):2725-32. doi: 10.1111/j.1572-0241.2002.07060.x.
A genetic locus for pediatric reflux was proposed on chromosome 13q14, but is unconfirmed in independent kindreds. We sought to test this locus in families with multiple affected infants from our database of well characterized infants with reflux.
We screened the database for families with multiple affected infants. Affected proband phenotype required histological esophagitis; affected sibling/cousin phenotype required a threshold score on a diagnostic questionnaire. Screened families were reduced to five based on pedigree, consent, and phenotypic clarity. Linkage of the phenotype with the four previously reported markers (D13S218, D13S1288, D13S1253, and D13S263) was tested, using an autosomal dominant, 70% penetrance model. Linkage required logarithm-of-odds score > or = 3.
Of 54 individuals in the five probands' generation, 21 (39%) were affected based on questionnaire, of whom nearly one half also had histological confirmation of esophagitis. Linkage to the defined region was excluded for the five families by two-point LOD scores (-1.47 at D13S218, -1.32 at D13S1288, -3.43 at D13S1253, and -3.92 at D13S263) and by multipoint (multipoint LOD scores less than -2 between D13S218 and D13S263) linkage analysis. No family demonstrated even suggestive positive linkage (i.e., LOD score >1).
In five rigorously phenotyped families with autosomal dominant pattern infantile reflux, we excluded genetic linkage to the region of 13ql4 previously identified responsible for an autosomal dominant form of pediatric reflux. These results suggest genetic heterogeneity, possibly related to phenotypic heterogeneity, in familial pediatric gastroesophageal reflux disease.
有人提出13号染色体长臂14区存在小儿胃食管反流的一个基因位点，但在独立家系中尚未得到证实。我们试图在我们特征明确的反流婴儿数据库中，对有多个患病婴儿的家庭进行该位点检测。
我们在数据库中筛选有多个患病婴儿的家庭。患病先证者的表型要求有组织学证实的食管炎；患病同胞/表亲的表型要求在诊断问卷上达到阈值分数。基于家系、知情同意和表型清晰度，筛选出的家庭减少到5个。使用常染色体显性、70%外显率模型，检测该表型与4个先前报道的标记物（D13S218、D13S1288、D13S1253和D13S263）的连锁关系。连锁要求优势对数分数≥3。
在5个先证者一代的54名个体中，根据问卷有21名（39%）患病，其中近一半也有食管炎的组织学证实。通过两点LOD分数（D13S218处为-1.47，D13S1288处为-1.32，D13S1253处为-3.43，D13S263处为-3.92）以及多点（D13S218和D13S263之间的多点LOD分数小于-2）连锁分析，排除了这5个家庭与定义区域的连锁关系。没有一个家庭表现出哪怕是提示性的阳性连锁（即LOD分数>1）。
在5个具有常染色体显性模式婴儿反流的严格表型家系中，我们排除了与先前确定的导致小儿胃食管反流常染色体显性形式的13q14区域的基因连锁关系。这些结果提示在家族性小儿胃食管反流病中存在基因异质性，可能与表型异质性有关。
