Soltani Banavandi M J, Kahrizi K, Behjati F, Mohseni M, Darvish H, Bahman I, Abedinni S S, Ghasemi Firouzabadi S, Jafari E, Ghadami Sh, Sabbagh F, Kavoosi Gh R, Najmabadi H
Faculty of Basic Science, Science and Research Branch, Islamic Azad University, Fars, Iran.
Iran Red Crescent Med J. 2012 Feb;14(2):79-85. Epub 2012 Feb 1.
Intellectual disability (ID) has a worldwide prevalence of 1-3% and results from extraordinary heterogeneous. To shed more light on the causes of ID in Kerman Province, in Southeast Iran, we set out in 2008 to perform systematic clinical studies and homozygosity mapping in large Iranian families with ID.
Fifty seven families with a minimum of two mentally retarded children from Kerman Province were initially tested for metabolic disorders, by Tandem mass spectrometry. Fragile X testing and standard karyotyping were performed for all probands of families. Cases with autosomal recessive (AR) pattern of inheritance and microcephaly were subjected to homozygosity mapping by using several microsatellite markers for known MCPH loci.
Three out of seven families with X-linked pattern of inheritance were positive for fragile X syndrome. Chromosome abnormality was not observed in any of dysmorphic patients and all families were negative for metabolic tests. Among the remaining 50 families of AR ID, six were found to be microcephalic, of which 2 linked to two MCPH loci (33.3%). The rest 4 families were not linked to any of the known loci.
The results of this study showed that ID with microcephaly comprised 12% of ID cases in Kerman Province. In two families with apparent linkage to the MCPH5 and MCPH6 locus, mutation screening was not successful, which might indicate that either the mutation is located in the regulatory sequences of the gene or that there might be another genes present in these regions, which is mutated in such cases.
智力障碍（ID）在全球的患病率为1%-3%，其病因极为多样。为了更深入了解伊朗东南部克尔曼省ID的病因，我们于2008年开始对伊朗大型ID家庭进行系统的临床研究和纯合性定位。
最初对来自克尔曼省的57个家庭（每个家庭至少有两个智障儿童）进行串联质谱法检测代谢紊乱情况。对所有家庭的先证者进行脆性X检测和标准核型分析。对于具有常染色体隐性（AR）遗传模式和小头畸形的病例，使用针对已知小头畸形原发性遗传性小头症（MCPH）基因座的几个微卫星标记进行纯合性定位。
在7个具有X连锁遗传模式的家庭中，有3个家庭的脆性X综合征检测呈阳性。在任何畸形患者中均未观察到染色体异常，所有家庭的代谢检测均为阴性。在其余50个AR ID家庭中，发现6个家庭有小头畸形，其中2个家庭与两个MCPH基因座相关（33.3%）。其余4个家庭与任何已知基因座均无关联。
本研究结果表明，小头畸形的ID占克尔曼省ID病例的12%。在两个与MCPH5和MCPH6基因座明显连锁的家庭中，突变筛查未成功这可能表明，要么突变位于基因的调控序列中，要么这些区域可能存在其他基因，在这种情况下这些基因发生了突变。
