Molecular genetic study of frontoethmoidal encephalocele in Indonesia

额筛样脑膨出（FEE）是一种神经管缺损（NID），其特征是前颅先天性骨缺损和颅内肿块通过缺损疝出。印度尼西亚人群的FEE发病率很高。2001-2002年，我们与婆罗威惹大学的一个研究小组在印度尼西亚东爪哇省玛琅研究了FEE患者。在本研究中，我们调查了FEE家族的背景，并在获得知情同意后进行了遗传分析。据报道，5,10 -亚甲基四氢叶酸还原酶基因（MTHFR）突变是NIDs的遗传危险因素。为了检验MTHFR与FEE发展之间的关系，我们对来自11个FEE家族的13名患者和8名母亲进行了MTHFR替代突变和多态性的基因组筛选。检测到的核苷酸替换（snp突变）为C121T、C677T、C1060T、A1298C和G1793A。在患者或母亲与对照组之间，核苷酸替换的频率没有显著差异。此外，没有受试者在核苷酸位置677处为T纯合子。综上所述，尽管本研究中分析的FEE家族数量非常有限，但MTHFR基因可能与FEE的发展无关。我们还研究了印尼爪哇人C677T突变的频率。突变等位基因和突变纯合子的频率在爪哇人群中都很低。据报道，一种假设认为，C677T突变的低频率与非洲NIDs的低发病率有关。然而，在印度尼西亚爪哇人中，尽管C677T突变的频率较低，但NID的一种形式FEE的发病率很高。最近，在小鼠中存在的Alx3和Alx4同源盒基因的复合突变体显示出严重的颅面异常。Alx3/Alx4双突变小鼠显示了一种提示性的FEE模型，尽管在我们的FEE患者中没有检测到Alx4基因突变。FEE的发展可能需要一组独立基因的突变，类似于我们在FEE患者中检测到的Alx3/Alx4基因双突变。FEE的发展可能需要类似Alx3/Alx4双突变小鼠的一组独立基因突变。如果是这样，那么确定FEE的遗传特征比确定单基因疾病要复杂得多。少

Frontoethmoidal encephalocele (FEE) is a neural tube defect (NID) characterized by a congenital bone defect in the anterior cranium and herniation of the intracranial mass through the defect. The Indonesian populations show high incidence of FEE. In 2001-2002, we studied FEE patients in Malang, East Java Province, Indonesia with a research group of Brawi jaya University. In this study, we investigated the background of the FEE families and carried out genetic analysis after obtaining informed consent.A mutation in the 5, 10-methylenetetrahydrofolate reductase gene (MTHFR) has been reported as a genetic risk factor for NIDs. To test the relationship between MTHFR and the development of FEE, we performed genomic screening of MTHFR substitutions mutations and polymorphisms in 13 patients and 8 mothers from 11 FEE families. Nucleotide substitutions (mutations of SNPs) detected were C121T, C677T, C1060T, A1298C, and G1793A. No significant differences were detected in the frequency of each n … More ucleotide substitution between patients or mothers and controls. In addition, none of the subjects tested were homozygous for T at nucleotide position 677. In conclusion, the MTHFR gene may not be associated with the development of FEE, although the number of FEE families analyzed in this study was very limited.We also studied the frequency of the C677T mutation in Indonesian Javanese. Both frequencies of the mutated allele and the mutated homozygotes were very low in the Javanese population. A hypothesis has been reported that low frequency of the C677T mutation is associated with the low incidence of NIDs in Africa. However, in Indonesian Javanese, a high incidence of a form of NID, FEE, has been seen in spite of a low frequency of the C677T mutation.Recently, the presence of compound mutants of the Alx3 and Alx4 homeobox genes in mice has shown severe craniofacial abnormalities. The Alx3/Alx4 double mutant mice shows a suggestive model of FEE, though no mutations were detected in the ALX4 gene in our FEE patients. The development of FEE may require a set of mutations in independent genes on the analogy of the Alx3/Alx4 double mutations were detected in the ALX4 gene in our FEE patients. The development of FEE may require a set of mutations in independent genes on the analogy of the Alx3/Alx4 double mutant mice. If so, it is much more complicated to determine the inheritance trait of FEE than a single gene disorder. Less