Winarni Tri Indah, Aishworiya Ramkumar, Culpepper Hannah, Zafarullah Marwa, Mendoza Guadalupe, Wilaisakditipakorn Tanaporn Jasmine, Likhitweerawong Narueporn, Law Julie, Hagerman Randi, Tassone Flora
Center for Biomedical Research (CEBIOR), Faculty of Medicine, Universitas Diponegoro, Semarang 50275, Central Java, Indonesia.
Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore 119074, Singapore.
Int J Mol Sci. 2025 Mar 21;26(7):2840. doi: 10.3390/ijms26072840.
We investigated the molecular and clinical profile of five boys carrying the fragile X messenger ribonucleoprotein 1 () mutation and who suffered from the effects of prenatal alcohol exposure. Fragile X syndrome (FXS) testing was performed using PCR and Southern Blot analysis, and fragile X messenger ribonucleoprotein protein (FMRP) expression levels were measured by Western blot analysis. Clinical evaluation included cognitive functions, adaptive skills, autism phenotype, and severity of behavior measures. Fetal Alcohol Spectrum Disorder (FASD) was also assessed. Five adopted male siblings were investigated, four of which (cases 1, 2, 3, and 4) were diagnosed with FXS, FASD, and ASD, and one, the fraternal triplet (case 5), was diagnosed with FASD and ASD and no FXS. The molecular profile of case 1 and 2 showed the presence of a hypermethylated full mutation (FM) and the resulting absence of FMRP. Cases 3 and 4 (identical twins) were FM-size mosaics (for the presence of an FM and a deleted allele), resulting in 16% and 50% FMRP expression levels, respectively. FMRP expression level was normal in case 5 (fraternal twin). Severe behavioral problems were observed in all cases, including aggression, tantrum, self-harming, anxiety, and defiant behavior, due to different mutations of the gene, in addition to biological exposure, home environmental factors, and potentially to additional background gene effects.
我们研究了五名携带脆性X信使核糖核蛋白1（FMR1）突变且受产前酒精暴露影响的男孩的分子和临床特征。使用聚合酶链反应（PCR）和Southern印迹分析进行脆性X综合征（FXS）检测，并通过蛋白质免疫印迹分析测量脆性X信使核糖核蛋白（FMRP）的表达水平。临床评估包括认知功能、适应技能、自闭症表型和行为测量的严重程度。还对胎儿酒精谱系障碍（FASD）进行了评估。对五名收养的男性兄弟姐妹进行了研究，其中四名（病例1、2、3和4）被诊断患有FXS、FASD和自闭症谱系障碍（ASD），另一名异卵三胞胎（病例5）被诊断患有FASD和ASD，但无FXS。病例1和2的分子特征显示存在高甲基化的全突变（FM），导致FMRP缺失。病例3和4（同卵双胞胎）是FM大小的嵌合体（存在FM和缺失等位基因），分别导致FMRP表达水平为16%和50%。病例5（异卵双胞胎）的FMRP表达水平正常。由于FMR1基因的不同突变，除了生物学暴露、家庭环境因素以及可能的其他背景基因效应外，所有病例均观察到严重的行为问题，包括攻击行为、发脾气、自我伤害、焦虑和违抗行为。
