Abstract：
Intellectual developmental disorder, X-linked 104 (XLID104), caused by the FRMPD4 gene variant, is a rare X-linked genetic disease that primarily manifests as intellectual disability (ID) and language delay, and may be accompanied by behavioural abnormalities. Currently, only 11 patients from four families have been reported to carry FRMPD4 gene variants. Here, we report a rare case of a Chinese patient with XLID104 who was presented with severe ID and language impairment. Genetic testing results showed that the patient had a novel hemizygous variant on FRMPD4 inherited from the heterozygous variant NM_001368397: c.1772A>C (p.Glu591Ala) carried by his mother. To our knowledge, this variant has not been reported previously. Western blot results for the recombinant plasmid constructed in vitro indicated that the expression of the mutant protein may be reduced. Using molecular dynamics simulations, we predicted that the mutant protein may affect the interaction of the FRMPD4 protein with DLG4. In this study, we expand the spectrum of FRMPD4 variants and suggest that the clinical awareness of the genetic diagnosis of nonsyndromic ID should be strengthened.
摘要：
智力发育障碍,X-linked104(XLID104),由FRMPD4基因变异引起，是一种罕见的X连锁遗传病，主要表现为智力障碍（ID）和语言延迟，并可能伴有行为异常。目前,据报道,来自4个家庭的仅11例患者携带FRMPD4基因变异.这里,我们报道了一例罕见的中国XLID104患者,其表现为严重的ID和语言障碍.遗传测试结果表明，该患者在FRMPD4上有一个新的半合子变体，该变体遗传自杂合变体NM_001368397：c.1772A>C（p。Glu591Ala）由他的母亲携带。据我们所知,这种变异以前没有报道过.体外构建的重组质粒的Westernblot结果表明，突变蛋白的表达可能降低。利用分子动力学模拟,我们预测突变蛋白可能会影响FRMPD4蛋白与DLG4的相互作用。在这项研究中,我们扩大了FRMPD4变异的范围,并建议应加强对非综合征型ID基因诊断的临床认识.
