Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, IBUB, IRSJD, CIBERER, Barcelona, Spain.
Geriatric Unit, Fondazione Ca'Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
Sci Rep. 2018 Jan 12;8(1):694. doi: 10.1038/s41598-017-19109-9.
De novo FOXP1 mutations have been associated with intellectual disability (ID), motor delay, autistic features and a wide spectrum of speech difficulties. C syndrome (Opitz C trigonocephaly syndrome) is a rare and genetically heterogeneous condition, characterized by trigonocephaly, craniofacial anomalies and ID. Several different chromosome deletions and and point mutations in distinct genes have been associated with the disease in patients originally diagnosed as Opitz C. By whole exome sequencing we identified a de novo splicing mutation in FOXP1 in a patient, initially diagnosed as C syndrome, who suffers from syndromic intellectual disability with trigonocephaly. The mutation (c.1428 + 1 G > A) promotes the skipping of exon 16, a frameshift and a premature STOP codon (p.Ala450GLyfs*13), as assessed by a minigene strategy. The patient reported here shares speech difficulties, intellectual disability and autistic features with other FOXP1 syndrome patients, and thus the diagnosis for this patient should be changed. Finally, since trigonocephaly has not been previously reported in FOXP1 syndrome, it remains to be proved whether it may be associated with the FOXP1 mutation.
新发现的 FOXP1 突变与智力障碍（ID）、运动发育迟缓、自闭症特征以及广泛的言语障碍有关。C 综合征（Opitz C 三角头综合征）是一种罕见的遗传异质性疾病，其特征为三角头、颅面异常和 ID。在最初被诊断为 Opitz C 的患者中，已经发现几种不同的染色体缺失和不同基因中的点突变与该疾病有关。通过全外显子组测序，我们在一名最初被诊断为 C 综合征的患者中发现了 FOXP1 的剪接突变，该患者患有伴有三角头的综合征性智力障碍。该突变（c.1428 + 1 G ＞ A）通过迷你基因策略促进了外显子 16 的跳跃、移码和提前终止密码子（p.Ala450GLyfs*13）。据报道，该患者与其他 FOXP1 综合征患者存在言语困难、智力障碍和自闭症特征，因此应改变对该患者的诊断。最后，由于三角头在 FOXP1 综合征中尚未被报道，因此仍需证明它是否可能与 FOXP1 突变有关。
