The oral-facial-digital syndrome type 1 (OFD1), a cause of polycystic kidney disease and associated malformations, maps to Xp22.2-Xp22.3
The oral-facial-digital syndrome type 1 (OFD1), a cause of polycystic kidney disease and associated malformations, maps to Xp22.2-Xp22.3
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DOI：
10.1093/hmg/6.7.1163
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发表时间：
1997-07-01
影响因子：
3.5
通讯作者：
Winter, RM
中科院分区：
文献类型：
--
作者：
Feather, SA;Woolf, AS;Winter, RM
1型口面指综合征（oral-facial-digital syndrome type 1，OFD 1）的主要特征包括面部、口腔和手指畸形，此外，临床表型通常包括精神发育迟滞和肾功能损害，约75%的OFD 1病例是散发性的，并且该病症几乎完全发生在女性中，在家族性病例中，最可能的遗传模式被认为是X-连锁显性，在受影响的男性中具有产前致死性。因此，OFD 1基因产物似乎在器官发生中具有广泛的重要性，并且对于胎儿存活是必需的，我们已经研究了两种肾病，其中临床病程主要是多囊肾病，需要透析和移植。我们使用沿X染色体间隔沿着约10 cM的多态性染色体标记，将该病定位于X染色体短臂上的一个区域（Xp22.2-Xp22.3）跨越19.8cM，并且侧翼为具有标记DXS 996和DX7 S105的交叉，在使用KAL基因内的标记的“仅受影响者”分析中，最大led得分为3.32（θ = 0.0），从而证实了OFD 1基因在X染色体上的位置，X染色体的其余部分被受影响个体中的重组体排除，我们的研究结果的重要性包括这种男性致死性疾病的X染色体的明确分配和人类多囊肾疾病的进一步基因座的定位。此外，该定位研究表明OFD 1作为X连锁显性Xpl突变体的可能小鼠模型，其中多指（趾）畸形和肾囊疾病发生，映射到小鼠X染色体的同源区域。
Key features of the oral-facial-digital syndrome type 1 (OFD1) include malformations of the face, oral cavity and digits, In addition, the clinical phenotype often includes mental retardation and renal functional impairment, Approximately 75% of cases of OFD1 are sporadic, and the condition occurs almost exclusively in females, In familial cases, the most likely mode of inheritance is considered to be X-linked dominant with prenatal lethality in affected males, Therefore, the OFD1 gene product appears to have widespread importance in organogenesis and is essential for fetal survival, We have studied two kindreds in which the clinical course was dominated by polycystic kidney disease requiring dialysis and transplantation. Using polymorphic chromosome markers spaced at similar to 10 cM intervals along the X chromosome, we mapped the disease to a region on the short arm of the X chromosome (Xp22.2-Xp22.3) spanning 19.8 cM and flanked by crossovers with the markers DXS996 and DX7S105, There was a maximum led score of 3.32 in an 'affecteds only' analysis using a marker within the KAL gene (theta = 0.0), thereby confirming the location of the gene for OFD1 on the X chromosome, The remainder of the X chromosome was excluded by recombinants in affected individuals, The importance of our findings includes the definitive assignment of this male-lethal disease to the X chromosome and the mapping of a further locus for a human polycystic kidney disease, Furthermore, this mapping study suggests a possible mouse model for OFD1 as the X-linked dominant Xpl mutant, in which polydactyly and renal cystic disease occurs, maps to the homologous region of the mouse X chromosome.