Celia’s encephalopathy (progressive encephalopathy with/without lipodystrophy (PELD)) is a childhood neurodegenerative disorder with a fatal prognosis before the age of 10, due to the variant c.985C>T in the BSCL2 gene that causes a cryptic splicing site leading to skipping of exon 7. For years, different authors have reported cases of congenital generalized lipodystrophy due to the variant c.974dupG in BSCL2 associated with neurological manifestations of variable severity, although some of them clearly superimposable to PELD. To identify the molecular mechanisms responsible for these neurological alterations in two patients with c.974dupG. Clinical characterization, biochemistry, and neuroimaging studies of two girls carrying this variant. In silico analysis, PCR amplification, and BSCL2 cDNA sequencing. BSCL2-201 transcript expression, which lacks exon 7, by qPCR in fibroblasts from the index case, from a healthy child as a control and from two patients with PELD, and in leukocytes from the index case and her parents. One with a severe encephalopathy including a picture of intellectual deficiency, severe language impairment, myoclonic epilepsy, and lipodystrophy as described in PELD, dying at 9 years and 9 months of age. The other 2-year-old patient showed incipient signs of neurological involvement. In silico and cDNA sequencing studies showed that variant c.974dupG gives rise to skipping of exon 7. The expression of BSCL2-201 in fibroblasts was significantly higher in the index case than in the healthy child, although less than in the case with homozygous PELD due to c.985C>T variant. The expression of this transcript was approximately half in the healthy carrier parents of this patient. The c.974dupG variant leads to the skipping of exon 7 of the BSCL2 gene and is responsible for a variant of Celia’s encephalopathy, with variable phenotypic expression.

中文翻译：

---

Celia的脑病和BSCL2基因中的c.974dupG：已知变体中的隐藏变化。

Celia脑病（伴或不伴脂肪营养不良（PELD）的进行性脑病）是一种儿童神经退行性疾病，由于BSCL2基因中的c.985C > T变异，会导致一个隐秘的剪接位点，从而导致跳过多年来，不同的作者报道了由于BSCL2中c.974dupG变异与严重程度不一的神经系统疾病相关的先天性全身脂肪营养不良的病例，尽管其中有些显然可以与PELD重叠。为了确定造成这些神经系统改变的两名c.974dupG患者的分子机制。两个携带这种变异病毒的女孩的临床表征，生物化学和神经影像学研究。计算机分析，PCR扩增和BSCL2 cDNA测序。通过qPCR，在来自标准病例的成纤维细胞，作为对照的健康儿童和两名PELD患者的成纤维细胞中，以及在标准病例及其父母的白细胞中，通过qPCR获得的BSCL2-201转录本表达，缺少外显子7。患有重度脑病的患者，如PELD中所述，包括智力缺陷，严重的语言障碍，肌阵挛性癫痫和脂肪营养不良，死于9岁和9个月大。另一位2岁的患者显示出神经系统受累的初期迹象。计算机和cDNA测序研究表明，c.974dupG变体引起外显子7的跳跃。BSCL2的表达尽管由于c.985C> T变体，纯合子PELD的情况比成年儿的成纤维细胞中的-201显着高于健康儿童。在该患者的健康携带者父母中，该转录物的表达约为一半。c.974dupG变体导致BSCL2基因的第7外显子跳过，并导致Celia脑病的一个变体，具有可变的表型表达。