Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy.
Dipartimento Degli Studi Umanistici, Università Degli Studi di Foggia, 71122 Foggia, Italy.
Genes (Basel). 2023 Oct 18;14(10):1958. doi: 10.3390/genes14101958.
The FOXP subfamily includes four different transcription factors: FOXP1, FOXP2, FOXP3, and FOXP4, all with important roles in regulating gene expression from early development through adulthood. Haploinsufficiency of , due to deleterious variants (point mutations, copy number variants) disrupting the gene, leads to an emerging disorder known as " syndrome", mainly characterized by intellectual disability, language impairment, dysmorphic features, and multiple congenital abnormalities with or without autistic features in some affected individuals (MIM 613670). Here we describe a 10-year-old female patient, born to unrelated parents, showing hypotonia, intellectual disability, and severe language delay. Targeted resequencing analysis allowed us to identify a heterozygous de novo variant c.1030C>T, p.(Gln344Ter) classified as likely pathogenetic according to the American College of Medical Genetics and Genomics guidelines. To the best of our knowledge, our patient is the first to date to report carrying this stop mutation, which is, for this reason, useful for broadening the molecular spectrum of clinically relevant variants. In addition, our results highlight the utility of next-generation sequencing in establishing an etiological basis for heterogeneous conditions such as neurodevelopmental disorders and providing additional insight into the phenotypic features of -related syndrome.
FOXP 亚家族包括四个不同的转录因子：FOXP1、FOXP2、FOXP3 和 FOXP4，它们在从早期发育到成年的基因表达调控中都具有重要作用。由于有害变异（点突变、拷贝数变异）破坏了基因，导致 FOXP2 单倍体不足，从而出现一种新兴的疾病，称为“FOXP2 综合征”，主要表现为智力残疾、语言障碍、发育异常特征，以及一些受影响个体的多种先天性异常，伴有或不伴有自闭症特征（MIM 613670）。在这里，我们描述了一位 10 岁女性患者，她出生于无亲缘关系的父母，表现为肌张力低下、智力残疾和严重的语言发育迟缓。靶向重测序分析使我们能够识别出杂合的新生突变 c.1030C>T，p.（Gln344Ter），根据美国医学遗传学与基因组学学院的指南，该突变被归类为可能的致病性突变。据我们所知，我们的患者是迄今为止第一个报告携带这种终止突变的患者，因此，该突变有助于拓宽 FOXP2 相关临床相关变异的分子谱。此外，我们的研究结果强调了下一代测序在为神经发育障碍等异质性疾病建立病因基础以及为 FOXP2 相关综合征的表型特征提供更多见解方面的实用性。
