Dai H, Zhang V W, El-Hattab A W, Ficicioglu C, Shinawi M, Lines M, Schulze A, McNutt M, Gotway G, Tian X, Chen S, Wang J, Craigen W J, Wong L-J
Baylor Genetics, Houston, TX, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Clin Genet. 2017 Apr;91(4):634-639. doi: 10.1111/cge.12894. Epub 2017 Jan 5.
Mutations in FBXL4 have recently been recognized to cause a mitochondrial disorder, with clinical features including early onset lactic acidosis, hypotonia, and developmental delay. FBXL4 sequence analysis was performed in 808 subjects suspected to have a mitochondrial disorder. In addition, 28 samples from patients with early onset of lactic acidosis, but without identifiable mutations in 192 genes known to cause mitochondrial diseases, were examined for FBXL4 mutations. Definitive diagnosis was made in 10 new subjects with a total of 7 novel deleterious variants; 5 null and 2 missense substitutions. All patients exhibited congenital lactic acidemia, most of them with severe encephalopathic presentation, and global developmental delay. Overall, FBXL4 defects account for at least 0.7% (6 out of 808) of subjects suspected to have a mitochondrial disorder, and as high as 14.3% (4 out of 28) in young children with congenital lactic acidosis and clinical features of mitochondrial disease. Including FBLX4 in the mitochondrial diseases panel should be particularly important for patients with congenital lactic acidosis.
最近发现，FBXL4基因突变会导致线粒体疾病，其临床特征包括早发性乳酸酸中毒、肌张力减退和发育迟缓。对808名疑似患有线粒体疾病的受试者进行了FBXL4序列分析。此外，对28例早发性乳酸酸中毒患者的样本进行了FBXL4基因突变检测，这些患者在已知可导致线粒体疾病的192个基因中未发现可识别的突变。最终确诊了10名新患者，共发现7种新的有害变异；5种无义突变和2种错义替代。所有患者均表现为先天性乳酸血症，大多数伴有严重的脑病表现和全面发育迟缓。总体而言，FBXL4缺陷在疑似患有线粒体疾病的受试者中占至少0.7%（808例中有6例），在患有先天性乳酸酸中毒且具有线粒体疾病临床特征的幼儿中高达14.3%（28例中有4例）。对于先天性乳酸酸中毒患者，将FBLX4纳入线粒体疾病检测尤为重要。
