PURPOSE Brain malformations caused by 17p13.3 deletions include lissencephaly with deletions of the larger Miller-Dieker syndrome region or smaller deletions of only PAFAH1B1, white matter changes, and a distinct syndrome due to deletions including YWHAE and CRK but sparing PAFAH1B1. We sought to understand the significance of 17p13.3 deletions between the YWHAE/CRK and PAFAH1B1 loci. METHODS We analyzed the clinical features of six individuals from five families with 17p13.3 deletions between and not including YWHAE/CRK and PAFAH1B1 identified among individuals undergoing clinical chromosomal microarray testing or research genome sequencing. RESULTS Five individuals from four families had multifocal white matter lesions while a sixth had a normal magnetic resonance image. A combination of our individuals and a review of those in the literature with white matter changes and deletions in this chromosomal region narrows the overlapping region for this brain phenotype to ~345 kb, including 11 RefSeq genes, with RTN4RL1 haploinsufficiency as the best candidate for causing this phenotype. CONCLUSION While previous literature has hypothesized dysmorphic features and white matter changes related to YWHAE, our cohort contributes evidence to the presence of additional genetic changes within 17p13.3 required for proper brain development.

中文翻译：

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不包括 YWHAE 和 PAFAH1B1 的微缺失会导致独特的白质脑病：进一步描述 17p13.3 微缺失谱。

目的 由 17p13.3 缺失引起的脑畸形包括具有较大 Miller-Dieker 综合征区域缺失或仅 PAFAH1B1 较小缺失的无脑畸形、白质变化以及由于包括 YWHAE 和 CRK 但保留 PAFAH1B1 缺失的独特综合征。我们试图了解 YWHAE/CRK 和 PAFAH1B1 基因座之间 17p13.3 缺失的重要性。方法 我们分析了来自五个家族的六个个体的临床特征，这些个体在接受临床染色体微阵列测试或研究基因组测序的个体中发现了 YWHAE/CRK 和 PAFAH1B1 之间的 17p13.3 缺失（不包括）。结果来自四个家庭的五个人患有多灶性白质病变，而第六人的磁共振图像正常。结合我们的个体和对该染色体区域白质变化和缺失的文献的回顾，将该大脑表型的重叠区域缩小至约 345 kb，包括 11 个 RefSeq 基因，其中 RTN4RL1 单倍体不足是导致这种表型。结论 虽然以前的文献假设了与 YWHAE 相关的畸形特征和白质变化，但我们的队列为正常大脑发育所需的 17p13.3 内存在额外的遗传变化提供了证据。