Institute of Biomedical Chemistry, Pogodinskaya street 10/8, 119121, Moscow, Russia.
Pirogov Russian National Research Medical University, Ostrovitianova street 1, 117997, Moscow, Russia.
BMC Med Genet. 2020 Oct 21;21(1):209. doi: 10.1186/s12881-020-01119-6.
Epilepsy with intellectual disability limited to females (Epileptic encephalopathy, early infantile, 9; EIEE9) is a rare early infantile epileptic encephalopathy characterized by an unusual X-linked inheritance: females with heterozygous mutations are affected, while hemizygous males are not.
We describe the clinical and molecular characteristics of 2 Russian patients with EIEE9 (females, ages 3 years and 7 years). In these patients seizures developed at the age of 3 years. Additionally, for our patients and for cases described in the literature we searched for a possible relationship between the type and localization of the mutation and the EIEE9 clinical phenotype.
We identified two novel PCDH19 mutations in EIEE9 patients: a missense mutation in exon 1 (c.1236C > A, p.Asp412Glu) and a frameshift in exon 3 (c.2386_2387insGTCT, p.Thr796fs). We conclude that the age of seizure onset and the presence of intellectual disability may depend not on the type and localization of PCDH19 mutations, but on the X-inactivation status. The study also highlights the need to screen for EIEE9 among young female epilepsy patients.
仅限于女性的伴智力障碍的癫痫（癫痫性脑病，早发性婴儿型，9 型；EIEE9）是一种罕见的早发性婴儿癫痫性脑病，其特征为一种不寻常的 X 连锁遗传方式：杂合突变的女性受影响，而半合子男性不受影响。
我们描述了 2 名俄罗斯 EIEE9 患者（女性，年龄分别为 3 岁和 7 岁）的临床和分子特征。在这些患者中，癫痫发作发生在 3 岁时。此外，我们还为这些患者以及文献中描述的病例，搜索了突变的类型和定位与 EIEE9 临床表型之间可能存在的关系。
我们在 EIEE9 患者中发现了两个新的 PCDH19 突变：一个位于外显子 1 的错义突变（c.1236C > A，p.Asp412Glu）和一个位于外显子 3 的移码突变（c.2386_2387insGTCT，p.Thr796fs）。我们得出结论，癫痫发作的年龄和智力障碍的存在可能不取决于 PCDH19 突变的类型和定位，而取决于 X 染色体失活状态。该研究还强调了在年轻女性癫痫患者中筛查 EIEE9 的必要性。
