Identification and characterization of genes in patients with severe mental retardation caused by autosomal dominant trait.

智力低下(MR)是导致儿童和年轻人严重残疾的最常见原因。MR的定义特征包括智商(智商)低于70，以及相关的适应行为功能缺陷，这些缺陷在18岁之前就会显现出来。MR背后的分子机制是非常不同的，大多数与MR有关的基因仍未确定。我们采用了确定两名严重精神发育迟滞患者的染色体易位断裂点的策略。位于易位断裂点的基因应该是MR的候选基因，这些情况可能是由常染色体显性性状引起的。1例患者(例1)的染色体易位介于2q22和13q22之间，另一例(例2)的染色体易位为6q16和12p12。例1患有严重智力低下、面部畸形、小头畸形、运动发育迟缓、先天性心脏病和先天性巨结肠，被诊断为先天性巨结肠-智力低下综合征。另一名患者有严重的智力低下和运动发育迟缓。我们已经确定ZFHX1B基因是导致HSCR-MR综合征的原因，位于2q22断裂点。我们还从病例2中确定了6q16上的易位断裂点。然而，我们的结果表明病例2的MR可能是由于位于12p12的基因缺陷所致。

Mental retardation (MR) is the most common cause of serious handicap in children and young adults. Defining features of MR include an IQ (intelligence quotient) of less than 70, together with associated functional deficits in adaptive behavior, which manifest themselves before 18 years of age. The molecular mechanisms underlying MR are quite heterogeneous and most of the genes responsible for MR are still unidentified. We have adopted the strategy of determining the chromosomal translocation breakpoints in two patients with profound mental retardation. Genes located at the translocation breakpoints should be candidates for MR and these conditions are likely caused by autosomal dominant traits. One patient (case 1 ) has a chromosomal translocation between 2q22 and 13q22 and the other (case 2) has 6q16 and 12p12. Case 1 has profound mental retardation, facial dysmorphism, microcephaly, delayed motor development, congenital heart disease and Hirschsprung disease, and was diagnosed as suffering from the Hirschsprung disease-Mental retardation (HSCR-MR) syndrome. The other patient has profound mental retardation and delayed motor development. We have identified ZFHX1B gene as a cause of the HSCR-MR syndrome, located at the 2q22 breakpoint. We also determined a translocation breakpoint on 6q16 from case 2. However our results suggest that the MR of case 2 is likely due to a defect in a gene located at 12p12.