坎帕尼亚地区(意大利)新生儿脊髓性肌萎缩症筛查项目:目前的局限性和潜在的前景。

IF 4 Q1 GENETICS & HEREDITY
Adelaide Ambrosio, Tiziana Fioretti, Barbara D'Andrea, Lucia Pezone, Ilaria Bitetti, Carmela Di Domenico, Sabrina Vallone, Valeria Maiolo, Angela Cioce, Mariano Giustino, Antonio Varone, Gabriella Esposito
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引用次数: 0

摘要

目前有三种针对脊髓性肌萎缩症(SMA)的靶向治疗方法,它们极大地改变了这种严重且可能致命的疾病的自然历史。超过95%的SMA病例有SMN1基因外显子7的纯合缺失。疾病表达主要取决于SMN1的一种亚型拷贝SMN2的拷贝数。世界上许多国家已经实施了新生儿筛查(NBS)计划,以早期识别和治疗患有SMA的儿童。我们在此介绍SMA NBS计划在坎帕尼亚的头两年结果,坎帕尼亚是意大利出生率最高的地区之一。从干血斑和外周血中提取基因组DNA。对于DBS,采用针对SMN1外显子7和内参基因(RPP30)的定量聚合酶链反应(qPCR)评估SMN1基因拷贝数。在阳性新生儿及其父母中,通过多重结扎探针扩增(MLPA)评估SMN1/SMN2拷贝数。我们分析了77,945名新生儿,并确定了11名阳性儿童。6名患者有2份SMN2,但只有1名患者在出生时表现出严重的sma相关体征。符合条件的新生儿在出生后20天内接受基因治疗。值得注意的是,qPCR未能在10/77,945 DBS中扩增到参考RPP30基因。尽管存在这种限制,我们观察到大约1/40 DBS的ΔCt值与一个SMN1拷贝的存在一致。在检测SMN1外显子7纯合缺失方面,SMA NBS的半自动化程序表现出优异的性能,除了少数没有扩增内参基因的情况。通过解决这一限制,筛选程序有可能检测SMN1缺失的杂合携带者,从而确定具有SMA生殖风险的家庭。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Newborn Screening Program for Spinal Muscular Atrophy in the Campania Region (Italy): Current Limitations and Potential Perspectives.

Newborn Screening Program for Spinal Muscular Atrophy in the Campania Region (Italy): Current Limitations and Potential Perspectives.

Newborn Screening Program for Spinal Muscular Atrophy in the Campania Region (Italy): Current Limitations and Potential Perspectives.

Newborn Screening Program for Spinal Muscular Atrophy in the Campania Region (Italy): Current Limitations and Potential Perspectives.

Three targeted therapies are currently available for spinal muscular atrophy (SMA), which have dramatically changed the natural history of this severe and potentially fatal disease. More than 95% of SMA cases have a homozygous deletion of exon 7 of the SMN1 gene. Disease expression mainly depends on the copy number of SMN2, a hypomorphic copy of SMN1. Many countries in the world have implemented newborn screening (NBS) programs for early identification and treatment of children with SMA. We herein present the first two-year results of the SMA NBS program in Campania, a region with one of the highest birth rates in Italy. Genomic DNA was extracted from dried blood spots (DBS) and peripheral blood. For DBS, the SMN1 gene copy number was evaluated by quantitative polymerase chain reaction (qPCR) targeting SMN1 exon 7 and a reference gene (RPP30). In positive newborns and their parents, SMN1/SMN2 copies were evaluated by multiplex ligation probe amplification (MLPA). We analyzed 77,945 newborns and identified 11 positive children. Six patients had 2 copies of SMN2, but only one showed severe SMA-related signs at birth. Eligible newborns were treated with gene therapy within 20 days of birth. Notably, qPCR failed to amplify the reference RPP30 gene in 10/77,945 DBS. Despite this limitation, we observed that about 1/40 DBS had ΔCt values consistent with the presence of one SMN1 copy. The semi-automated procedure used for SMA NBS showed excellent performance in detecting the presence of homozygous deletion of SMN1 exon 7, with the exception of a few cases with the absence of amplification of the reference gene. By solving this limitation, the screening procedure has the potential to detect heterozygous carriers of the SMN1 deletion and, consequently, identify families at procreative risk of SMA.

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来源期刊
International Journal of Neonatal Screening
International Journal of Neonatal Screening Medicine-Pediatrics, Perinatology and Child Health
CiteScore
6.70
自引率
20.00%
发文量
56
审稿时长
11 weeks
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