Albanyan Saleh, Al Teneiji Amal, Monfared Nasim, Mercimek-Mahmutoglu Saadet
Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
Genetics and Genome Biology Research Program, Research Institute, The Hospital for Sick Children, Toronto, Canada.
Am J Med Genet A. 2017 Jun;173(6):1640-1643. doi: 10.1002/ajmg.a.38127. Epub 2017 Mar 23.
BCAP31, encoded by BCAP31, is involved in the export of transmembrane proteins from the endoplasmic reticulum. Pathogenic variants in BCAP31 results in global developmental delay, dystonia, deafness and dysmorphic features in males, called deafness, dystonia, and cerebral hypomyelination (DDCH) syndrome. We report a new patient with BCAP3-associated encephalopathy, DDCH syndrome, sensorineural hearing loss, generalized dystonia, and choreoathetosis. This 3.5-year-old boy had microcephaly and failure to thrive within the first 3 months of life. His brain MRI showed bilateral increased signal intensity in globus pallidus at age 3 months raising the suspicion of mitochondrial encephalopathy. His muscle biopsy revealed pleomorphic subsarcolemmal mitochondria collection in electron microscopy. Respiratory chain enzyme activities were normal in muscle. He was enrolled to a whole exome sequencing research study, which identified a hemizygous likely pathogenic truncating variant (c.533_536dup; p.Ser180AlafsX6) in BCAP31, inherited from his mother, who had sensorineural hearing loss and normal cognitive functions. We report a new patient with BCAP31-associated encephalopathy, DDCH syndrome, mimicking mitochondrial encephalopathy. We also report a heterozygous mother who has bilateral sensorineural hearing loss. This patient's clinical features, muscle histopathology, brain MRI features, and family history were suggestive of mitochondrial encephalopathy. Whole exome sequencing research study confirmed the diagnosis of BCAP31-associated encephalopathy, DDCH syndrome.
由BCAP31基因编码的BCAP31参与跨膜蛋白从内质网的输出过程。BCAP31的致病变异会导致男性出现全面发育迟缓、肌张力障碍、耳聋和畸形特征，称为耳聋、肌张力障碍和脑白质发育不全（DDCH）综合征。我们报告了一名患有BCAP3相关脑病、DDCH综合征、感音神经性听力损失、全身性肌张力障碍和舞蹈手足徐动症的新患者。这名3.5岁男孩在出生后的头3个月内出现小头畸形和发育不良。他3个月大时的脑部磁共振成像显示双侧苍白球信号强度增加，这引发了线粒体脑病的怀疑。他的肌肉活检在电子显微镜下显示肌膜下线粒体呈多形性聚集。肌肉中的呼吸链酶活性正常。他参加了一项全外显子组测序研究，该研究在BCAP31基因中鉴定出一个半合子可能致病的截短变异（c.533_536dup；p.Ser180AlafsX6），该变异遗传自他的母亲，他的母亲有感音神经性听力损失但认知功能正常。我们报告了一名患有BCAP31相关脑病、DDCH综合征且酷似线粒体脑病的新患者。我们还报告了一位患有双侧感音神经性听力损失的杂合子母亲。该患者的临床特征、肌肉组织病理学、脑部磁共振成像特征和家族史提示为线粒体脑病。全外显子组测序研究证实了BCAP31相关脑病、DDCH综合征的诊断。
