Molinari F, Kaminska A, Fiermonte G, Boddaert N, Raas-Rothschild A, Plouin P, Palmieri L, Brunelle F, Palmieri F, Dulac O, Munnich A, Colleaux L
Laboratoire de génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (INSERM U781), Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France.
Clin Genet. 2009 Aug;76(2):188-94. doi: 10.1111/j.1399-0004.2009.01236.x.
Neonatal epileptic encephalopathies with suppression bursts (SBs) are very severe and relatively rare diseases characterized by neonatal onset of seizures, interictal electroencephalogram (EEG) with SB pattern and very poor neurological outcome or death. Their etiology remains elusive but they are occasionally caused by metabolic diseases or malformations. Studying an Arab Muslim Israeli consanguineous family, with four affected children presenting a severe neonatal epileptic encephalopathy, we have previously identified a mutation in the SLC25A22 gene encoding a mitochondrial glutamate transporter. In this report, we describe a novel SLC25A22 mutation in an unrelated patient born from first cousin Algerian parents and presenting severe epileptic encephalopathy characterized by an EEG with SB, hypotonia, microcephaly and abnormal electroretinogram. We showed that this patient carried a homozygous p.G236W SLC25A22 mutation which alters a highly conserved amino acid and completely abolishes the glutamate carrier's activity in vitro. Comparison of the clinical features of patients from both families suggests that SLC25A22 mutations are responsible for a novel clinically recognizable epileptic encephalopathy with SB.
伴有抑制爆发（SBs）的新生儿癫痫性脑病是非常严重且相对罕见的疾病，其特征为新生儿期起病的癫痫发作、发作间期脑电图（EEG）呈现SB模式以及神经学预后极差或死亡。其病因仍不明确，但偶尔由代谢性疾病或畸形引起。在研究一个阿拉伯穆斯林以色列近亲家庭时，该家庭有四个患病孩子表现为严重的新生儿癫痫性脑病，我们之前在编码线粒体谷氨酸转运体的SLC25A22基因中鉴定出一个突变。在本报告中，我们描述了一名无关患者中的一种新的SLC25A22突变，该患者由阿尔及利亚近亲父母所生，表现为严重的癫痫性脑病，其特征为EEG呈现SB、肌张力减退、小头畸形和视网膜电图异常。我们发现该患者携带纯合的p.G236W SLC25A22突变，该突变改变了一个高度保守的氨基酸，并在体外完全消除了谷氨酸载体的活性。对两个家庭患者临床特征的比较表明，SLC25A22突变导致了一种新的临床上可识别的伴有SB的癫痫性脑病。
