PDF(Pubmed)
Abstract：
The OTUD6B and ZMIZ1 genes were recently identified as causes of syndromic intellectual disability (ID) with shared phenotypes of facial dysmorphism, distal limb anomalies, and seizure disorders. OTUD6B- and ZMIZ1-related ID are inherited in autosomal recessive and autosomal dominant patterns, respectively. We report a 5-year-old girl with developmental delay, facial phenotypes resembling Williams syndrome, and cardiac defects. The patient also had terminal broadening of the fingers and polydactyly. Cytogenomic microarray (CMA), whole exome sequencing (WES), and mRNA analysis were performed. The CMA showed a paternally inherited 0.118 Mb deletion of 8q21.3, chr8:92084087-92202189, with OTUD6B involved. The WES identified a hemizygous OTUD6B variant, c.873delA (p.Lys291AsnfsTer3). The mother was heterozygous for this allele. The WES also demonstrated a heterozygous ZMIZ1 variant, c.1491 + 2T > C, in the patient and her father. This ZMIZ1 variant yielded exon 14 skipping, as evidenced by mRNA study. We suggest that Williams syndrome-like phenotypes, namely, periorbital edema, hanging cheek, and long and smooth philtrum represent expanded phenotypes of OTUD6B-related ID. Our data expand the genotypic spectrum of OTUD6B- and ZMIZ1-related disorders. This is the first reported case of a compound heterozygote featuring point mutation, chromosomal microdeletion of OTUD6B, and the unique event of OTUD6B, coupled with ZMIZ1 variants.
摘要：
OTUD6B和ZMIZ1基因最近被确定为具有面部畸形的共同表型的综合征性智力障碍（ID）的原因，远端肢体异常,和癫痫症。OTUD6B和ZMIZ1相关的ID以常染色体隐性和常染色体显性模式遗传，分别。我们报告了一个发育迟缓的5岁女孩，类似威廉姆斯综合征的面部表型，和心脏缺陷。患者还出现了手指末端变宽和多指畸形。细胞基因组微阵列（CMA），全外显子组测序（WES），并进行mRNA分析。CMA显示8q21.3，chr8：92084087-92202189的父系遗传0.118Mb缺失，涉及OTUD6B。WES鉴定出半合子OTUD6B变体，c.873delA（p。Lys291AsnfsTer3）。母亲对该等位基因是杂合的。WES还证明了一个杂合的ZMIZ1变体，c.1491+2T>C，病人和她的父亲。这个ZMIZ1变体产生了外显子14跳跃，mRNA研究证明。我们建议威廉姆斯综合征样表型，即,眶周水肿,挂着脸颊，长而光滑的hiltrum代表OTUD6B相关ID的扩展表型。我们的数据扩展了OTUD6B和ZMIZ1相关疾病的基因型谱。这是首例以点突变为特征的复合杂合子，OTUD6B的染色体微缺失，以及OTUD6B的独特事件，加上ZMIZ1变体。
