PDF(Pubmed)
Abstract：
BACKGROUND: Multisystemic findings of inherited bone marrow failure syndromes may cause difficulty in diagnosis. Exome sequencing (ES) helps to define the etiology of rare diseases and reanalysis offers a valuable new diagnostic approach. Herein, we present the clinical and molecular characteristics of a girl who was referred for cytopenia and frequent infections.
METHODS: A 5-year-old girl with cytopenia, dysmorphism, short stature, developmental delay, and myopia was referred for genetic counseling. Reanalysis of the ES data revealed a homozygous splice-site variant in the DNAJC21 (NM_001012339.3:c.983+1G>A), causing Shwachman-Diamond Syndrome (SDS). It was shown by the RNA sequencing that exon 7 was skipped, causing an 88-nucleotide deletion.
CONCLUSIONS: Precise genetic diagnosis enables genetic counseling and improves patient management by avoiding inappropriate treatment and unnecessary testing. This report would contribute to the clinical and molecular understanding of this rare type of SDS caused by DNAJC21 variants and expand the phenotypic features of this condition.
METHODS: A 5-year-old girl with cytopenia, dysmorphism, short stature, developmental delay, and myopia was referred for genetic counseling. Reanalysis of the ES data revealed a homozygous splice-site variant in the DNAJC21 (NM_001012339.3:c.983+1G>A), causing Shwachman-Diamond Syndrome (SDS). It was shown by the RNA sequencing that exon 7 was skipped, causing an 88-nucleotide deletion.
CONCLUSIONS: Precise genetic diagnosis enables genetic counseling and improves patient management by avoiding inappropriate treatment and unnecessary testing. This report would contribute to the clinical and molecular understanding of this rare type of SDS caused by DNAJC21 variants and expand the phenotypic features of this condition.
摘要：
背景：遗传性骨髓衰竭综合征的多系统发现可能导致诊断困难。外显子组测序（ES）有助于确定罕见疾病的病因，重新分析提供了一种有价值的新诊断方法。在这里，我们介绍了一名因血细胞减少和频繁感染而转诊的女孩的临床和分子特征。
方法：一名5岁女孩患有血细胞减少症，畸形,身材矮小,发育迟缓,近视被转诊为遗传咨询。ES数据的重新分析揭示了DNAJC21中的纯合剪接位点变体(NM_001012339.3:c.983+1G>A),导致Shwachman-Diamond综合征(SDS)RNA测序显示外显子7被跳过，导致88个核苷酸的缺失.
结论：精确的基因诊断可以提供遗传咨询，并通过避免不适当的治疗和不必要的检测来改善患者管理。该报告将有助于对由DNAJC21变体引起的这种罕见类型的SDS的临床和分子理解，并扩大这种情况的表型特征。
方法：一名5岁女孩患有血细胞减少症，畸形,身材矮小,发育迟缓,近视被转诊为遗传咨询。ES数据的重新分析揭示了DNAJC21中的纯合剪接位点变体(NM_001012339.3:c.983+1G>A),导致Shwachman-Diamond综合征(SDS)RNA测序显示外显子7被跳过，导致88个核苷酸的缺失.
结论：精确的基因诊断可以提供遗传咨询，并通过避免不适当的治疗和不必要的检测来改善患者管理。该报告将有助于对由DNAJC21变体引起的这种罕见类型的SDS的临床和分子理解，并扩大这种情况的表型特征。
