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目的:在2个无患儿生物学标本的火棉胶样婴儿家庭中确定致病基因突变位点,并为其提供产前诊断。方法:收集已逝火棉胶样婴儿临床病史,依据引起该病的候选致病基因进行排序,在患儿父母中逐一进行候选致病基因突变位点检测。确定突变位点后,分别在孕11周和孕18周时进行胎儿绒毛膜及羊水穿刺,对胎儿DNA进行致病突变位点检测,确定其基因型及患病情况。结果:两个家庭中分别分娩过2例和1例火棉胶样婴儿,均在出生不久后夭折,未能获取患儿任何生物学标本。笔者在家庭1的健康父母中分别发现TGM1基因c.C427T及c.1106delG杂合突变;在家庭2的健康父母中分别发现ALOX12B基因c.1463G>A和c.1642C>T杂合突变。再次怀孕后,家庭1的胎儿绒毛膜组织标本未检测到TGM1的任一致病突变位点:家庭2的胎儿羊水标本中检测到c.1463G>A突变,但未发现c.1642C>T突变,诊断该胎儿为健康携带者。两个家庭胎儿出生后均为健康婴儿。结论:虽然多数火棉胶样婴儿病情危重,可导致早夭,但可根据该病的候选致病基因排查结果在缺乏患儿DNA标本的家庭中进行基因诊断和产前诊断。
OBJECTIVE: To determine the site of disease-causing gene mutations in two confocal-like infant families without biological samples and provide prenatal diagnosis. Methods: The clinical history of coca-jelly-like infants was collected and sorted according to the candidate pathogenic genes that cause the disease. Mutations in candidate pathogenic genes were detected one by one in the parents of the children. After identifying the mutation sites, fetus chorionic and amniotic fluid punctures were performed at 11 weeks of gestation and 18 weeks of gestation respectively. The fetal DNA was tested for pathogenic mutation sites to determine its genotype and prevalence. RESULTS: Two cases of babies delivered in each of the two families and one case of pyrocarbons were both born shortly after birth and failed to obtain any biological samples from children. The author found heterozygous mutation of c.C427T and c.1106delG in TGM1 gene in healthy parents of family 1. Mutant mutations in c.1463G> A and c.1642C> T of ALOX12B gene were detected in healthy family 2, respectively. After a second pregnancy, none of the fetal chorionic tissue samples of family 1 detected any of the disease-causing mutation sites for TGM1: the c.1463G> A mutation was detected in the fetal amniotic fluid sample of family 2 but no c.1642C> T mutation was found , Diagnose the fetus as a healthy carrier. Both families are healthy babies after birth. CONCLUSIONS: Although most collombrin-like infants are critically ill and lead to premature death, genetic diagnosis and prenatal diagnosis can be performed in families lacking DNA samples from the screening of candidate pathogenic genes.