Rinaldi Berardo, Van Hoof Evelien, Corveleyn Anniek, Van Cauter Annick, de Ravel Thomy
University of Milan, Milan, Italy.
Center for Human Genetics, University Hospitals Leuven, Catholic University Leuven, Leuven, Belgium.
Eur J Med Genet. 2020 Feb;63(2):103732. doi: 10.1016/j.ejmg.2019.103732. Epub 2019 Jul 19.
Pathogenic variants in the BCAP31 gene have recently been associated with a severe congenital neurological phenotype, named DDCH after its key features: deafness, dystonia and central hypomyelination. BCAP31 is located at the Xq28 chromosomal region and only male individuals are currently known to be affected, the pathogenic variant being usually transmitted by healthy mothers. Here, we describe a three-year-old male child referred for severe developmental delay, failure to thrive, hearing loss and dyskinetic movements. After a conventional diagnostic workflow, including a normal array-CGH, a tentative diagnosis of dyskinetic cerebral palsy was retained. Clinical exome sequencing in the trio identified a small intragenic deletion in exon 8 of BCAP31, c.709_721del (p.Val237Trpfs*69), originated de novo and not previously reported. Based on the ACMG variant classification, this variant is predicted to be 'likely pathogenic'. Given the consistent phenotypical overlap with the subjects already ascertained with DDCH, we considered this variant to be clinically relevant for this child and causative of his condition.
BCAP31基因的致病性变异最近与一种严重的先天性神经表型相关，该表型因其关键特征（耳聋、肌张力障碍和中枢性髓鞘形成不足）而被命名为DDCH。BCAP31位于Xq28染色体区域，目前已知只有男性个体受影响，致病性变异通常由健康母亲遗传。在此，我们描述了一名3岁男童，因严重发育迟缓、生长发育不良、听力丧失和运动障碍前来就诊。经过包括正常阵列比较基因组杂交在内的常规诊断流程后，初步诊断为运动障碍型脑瘫。对该三口之家进行临床外显子组测序，在BCAP31基因第8外显子中发现一个小的基因内缺失，即c.709_721del（p.Val237Trpfs*69），该缺失为新发且此前未报道过。根据美国医学遗传学与基因组学学会（ACMG）的变异分类，该变异被预测为“可能致病”。鉴于该患儿与已确诊的DDCH患者在表型上存在一致的重叠，我们认为该变异与该患儿的临床情况相关且是其病因。
