Inherited deletion of 9p22.3-p24.3 and duplication of 18p11.31-p11.32 associated with neurodevelopmental delay: Phenotypic matching of involved genes.
Inherited deletion of 9p22.3-p24.3 and duplication of 18p11.31-p11.32 associated with neurodevelopmental delay: Phenotypic matching of involved genes.
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DOI：
10.1111/jcmm.17662
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发表时间：
2023-02
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
我们报道了一名3.5岁的伊朗女童及其10个月大同样患病的弟弟，他们携带一条母系遗传的9号衍生染色体[der(9)]。通过阵列比较基因组杂交（aCGH）分析对出生后检测到的染色体重排进行了精细表征，结果显示9p22.3 - p24.3p22.3区域有15.056 Mb的缺失，涵盖14个《人类孟德尔遗传在线》（OMIM）致病基因，如DOCK8、KANK1、DMRT1和SMARCA2，同时18p11.31 - p11.32区域有3.309 Mb的增加，涵盖USP14、THOC1、COLEC12、SMCHD1和LPIN2。我们使用PhenogramViz将检测到的拷贝数变异（CNV）所影响的基因与临床和功能表型特征进行比对。在这方面，将患者的表型和CNV数据输入到PhenogramViz中。对于9p缺失CNV，鉴定出53个受影响基因，其中17个与描述患者表型的24个人类表型本体（HPO）术语相匹配。此外，对于18p重复CNV，鉴定出22个受影响基因，其中6个与13种表型相匹配。此外，我们使用DECIPHER对检测到的CNV中涉及的基因进行深入表征，并将患者表型与9p和18p基因组失衡情况进行比较。根据我们的筛选策略，在9p22.3 - p24.3区域，DECIPHER中有约80个致病性/可能致病性/不确定的重叠CNV。这些CNV的大小范围从12.01 kb到18.45 Mb，其中52个CNV大小小于1 Mb，影响10个OMIM致病基因。18p11.31 - p11.32区域与DECIPHER数据库中的19个CNV重叠，大小范围从23.42 kb到1.82 Mb。这些CNV影响8个单倍体不足基因。
We describe a 3.5‐year‐old Iranian female child and her affected 10‐month‐old brother with a maternally inherited derivative chromosome 9 [der(9)]. The postnatally detected rearrangement was finely characterized by aCGH analysis, which revealed a 15.056 Mb deletion of 9p22.3‐p24.3p22.3 encompassing 14 OMIM morbid genes such as DOCK8, KANK1, DMRT1 and SMARCA2, and a gain of 3.309 Mb on 18p11.31‐p11.32 encompassing USP14, THOC1, COLEC12, SMCHD1 and LPIN2. We aligned the genes affected by detected CNVs to clinical and functional phenotypic features using PhenogramViz. In this regard, the patient's phenotype and CNVs data were entered into PhenogramViz. For the 9p deletion CNV, 53 affected genes were identified and 17 of them were matched to 24 HPO terms describing the patient's phenotypes. Also, for CNV of 18p duplication, 22 affected genes were identified and six of them were matched to 13 phenotypes. Moreover, we used DECIPHER for in‐depth characterization of involved genes in detected CNVs and also comparison of patient phenotypes with 9p and 18p genomic imbalances. Based on our filtration strategy, in the 9p22.3‐p24.3 region, approximately 80 pathogenic/likely pathogenic/uncertain overlapping CNVs were in DECIPHER. The size of these CNVs ranged from 12.01 kb to 18.45 Mb and 52 CNVs were smaller than 1 Mb in size affecting 10 OMIM morbid genes. The 18p11.31‐p11.32 region overlapped 19 CNVs in the DECIPHER database with the size ranging from 23.42 kb to 1.82 Mb. These CNVs affect eight haploinsufficient genes.
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