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Maternity Care Providers' Experiences with Providing Information on Newborn Bloodspot Screening During Pregnancy: A Dutch Survey Study.
IF 4 Q1 GENETICS & HEREDITY Pub Date : 2025-01-08 DOI: 10.3390/ijns11010005
Jasmijn E Klapwijk, Janneke Gitsels-van der Wal, Linda Martin, Rendelien K Verschoof-Puite, Ellen Elsinghorst, Lidewij Henneman

Newborn bloodspot screening (NBS) aims to detect treatable disorders in newborns to offer early interventions. According to the official Dutch national NBS guidance, parents in the Netherlands should be informed about NBS during pregnancy by maternity care providers (MCPs), providing two leaflets and oral information. This study investigated what, how, and when information about NBS is given during pregnancy according to Dutch MCPs. An online questionnaire was completed by 279 MCPs; 237 (84.9%) provided information to parents themselves, although 4.6% of them only did so postnatally, and 240 (86.0%) considered this the task of the MCP. Among the 237 MCPs, information was provided by personal conversation (59.9%) and by giving at least one leaflet (83.1%), while 25.7% only gave leaflets. Being a first pregnancy (45.1%) and parents' literacy (38.8%) influenced how MCPs provided information. Information was mostly provided at 34-37 weeks gestation (68.8%). Conversations mostly included giving information on when NBS will be performed (97.2%), the purpose of NBS (93.7%), how the test will be performed (92.3%), and participation being voluntary (80.3%). The results suggest that while most Dutch MCPs consider it their task to provide NBS information, its timing, method, and completeness do not always follow the established guidelines.

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引用次数: 0
Parent Reports of Developmental Service Utilization After Newborn Screening.
IF 4 Q1 GENETICS & HEREDITY Pub Date : 2024-12-31 DOI: 10.3390/ijns11010003
Elizabeth Reynolds, Sarah Nelson Potter, Samantha Scott, Donald B Bailey

Newborn screening (NBS) presents an opportunity to identify a subset of babies at birth who are at risk for developmental delays and could benefit from a range of developmental services. Potential developmental services in the United States include Part C Early Intervention (EI), private therapies, and school-based services. Using parent-reported outcomes, this study examined the rates at which a sample of children diagnosed with NBS conditions used each developmental service. An online survey of 153 parents representing children with 27 different NBS conditions found that nearly 75% of children (n = 112) used at least one developmental service, with private therapies being the most frequent. Children were referred to EI relatively early and were often eligible because their medical diagnosis automatically qualified them. When examining condition-specific results for children with severe combined immunodeficiencies, congenital hypothyroidism, and Pompe disease, we found variability in rates of use, with high rates overall. Our findings suggest that many children diagnosed with an NBS condition continue to have developmental delays even after they receive appropriate medical care. Future research with more systematic follow-up is needed to understand whether the NBS program facilitates entry into these services and whether more streamlined processes could benefit children and families.

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引用次数: 0
Consolidated Newborn Bloodspot Screening Efforts in Developing Countries in the Asia Pacific-2024.
IF 4 Q1 GENETICS & HEREDITY Pub Date : 2024-12-30 DOI: 10.3390/ijns11010002
Bradford L Therrell, Carmencita D Padilla, Michelle E Abadingo, Shree Prasad Adhikari, Thuza Aung, Thet Thet Aye, Sanjoy Kumer Dey, Muhammad Faizi, Erdenetuya Ganbaatar, Tran Thi Huong Giang, Hoang Thu Hang, Rathmony Heng, Seema Kapoor, Khurelbaatar Nyamdavaa, Prajwal Paudel, Kimyi Phou, Aman B Pulungan, Chittaphone Sayyavong, Salimah R Walani, Tariq Zafar

Approximately half of all births globally occur in the Asia Pacific Region. Concerted efforts to support local activities aimed at developing national newborn screening (NBS) have been ongoing for almost 30 years, first by the International Atomic Energy Agency (IAEA) and then through volunteer efforts. Sustainable newborn bloodspot screening (NBS) continues to be initiated and develop in many of the countries with developing economies in the region. Since the discontinuation of IAEA funding in 2007, a working group of the Asia Pacific Society of Human Genetics (APSHG) consisting of interested representatives from countries in the region with less than 50% NBS coverage has participated in periodic workshops to exchange information, set goals, and provide peer support. Facilitated by international NBS experts, interested corporate sponsors, and the APSHG, the 7th workshop of representatives from 10 East Asian countries with developing NBS systems was recently held in Kathmandu, Nepal. This report summarizes the NBS activities in these countries and describes the continuing efforts to move NBS ahead in the region.

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引用次数: 0
Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability.
IF 4 Q1 GENETICS & HEREDITY Pub Date : 2024-12-28 DOI: 10.3390/ijns11010001
Abigail Veldman, Birgit Sikkema-Raddatz, Terry G J Derks, Clara D M van Karnebeek, M B Gea Kiewiet, Margaretha F Mulder, Marcel R Nelen, M Estela Rubio-Gozalbo, Richard J Sinke, Monique G de Sain-van der Velden, Gepke Visser, Maaike C de Vries, Dineke Westra, Monique Williams, Ron A Wevers, M Rebecca Heiner-Fokkema, Francjan J van Spronsen

The biomarker-based Dutch Newborn Screening (NBS) panel (as of 2024) comprises 19 inherited metabolic disorders (IMDs). With the use of next-generation sequencing (NGS) as a first-tier screen, NBS could expand to include IMDs that lack a reliable biochemical footprint in dried blood spots, while also reducing secondary findings. To be eligible for inclusion in NBS, an IMD needs to fulfill the Wilson and Jungner criteria, with treatability being one of the most important criteria. In this study, we aimed to identify IMDs eligible for DNA-first NBS when considering only treatability in the context of NBS as a prerequisite. First, three independent reviewers performed a systematic literature review of the 1459 genotypic IMDs and their causative gene(s), as described in the International Classification of Inherited Metabolic Disorders (dated 1 February 2021), applying 16 criteria to exclude non-treatable disorders. Eligible disorders were then discussed in three online meetings with a project group of clinical laboratory geneticists, medical laboratory specialists specialized in IMD, and pediatricians with expertise in IMDs. Based on treatability, we identified 100 genes, causing 95 IMDs, as eligible for NBS, including 42 causal genes for the IMDs in the current biomarker-based NBS. The other 58 genes are primarily associated with treatable defects in amino acid metabolism and fatty acid oxidation. Other IMDs were excluded, most often because of insufficient literature. As the evaluation of treatability was not straightforward, we recommend the development of standardized treatability scores for the inclusion of IMDs in NBS.

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引用次数: 0
Digital-Tier Strategy Improves Newborn Screening for Glutaric Aciduria Type 1. 数字层策略改善新生儿戊二酸尿1型筛查。
IF 4 Q1 GENETICS & HEREDITY Pub Date : 2024-12-21 DOI: 10.3390/ijns10040083
Elaine Zaunseder, Julian Teinert, Nikolas Boy, Sven F Garbade, Saskia Haupt, Patrik Feyh, Georg F Hoffmann, Stefan Kölker, Ulrike Mütze, Vincent Heuveline

Glutaric aciduria type 1 (GA1) is a rare inherited metabolic disease increasingly included in newborn screening (NBS) programs worldwide. Because of the broad biochemical spectrum of individuals with GA1 and the lack of reliable second-tier strategies, NBS for GA1 is still confronted with a high rate of false positives. In this study, we aim to increase the specificity of NBS for GA1 and, hence, to reduce the rate of false positives through machine learning methods. Therefore, we studied NBS profiles from 1,025,953 newborns screened between 2014 and 2023 at the Heidelberg NBS Laboratory, Germany. We identified a significant sex difference, resulting in twice as many false-positives male than female newborns. Moreover, the proposed digital-tier strategy based on logistic regression analysis, ridge regression, and support vector machine reduced the false-positive rate by over 90% compared to regular NBS while identifying all confirmed individuals with GA1 correctly. An in-depth analysis of the profiles revealed that in particular false-positive results with high associated follow-up costs could be reduced significantly. In conclusion, understanding the origin of false-positive NBS and implementing a digital-tier strategy to enhance the specificity of GA1 testing may significantly reduce the burden on newborns and their families from false-positive NBS results.

戊二酸尿1型(GA1)是一种罕见的遗传性代谢性疾病,越来越多地被纳入新生儿筛查(NBS)项目。由于GA1患者具有广泛的生化谱,并且缺乏可靠的二级策略,因此GA1的NBS仍然面临着很高的假阳性率。在本研究中,我们的目标是提高NBS对GA1的特异性,从而通过机器学习方法降低误报率。因此,我们研究了2014年至2023年在德国海德堡NBS实验室筛查的1,025,953名新生儿的NBS资料。我们发现了显著的性别差异,导致男婴的假阳性是女婴的两倍。此外,所提出的基于逻辑回归分析、岭回归和支持向量机的数字层策略与常规NBS相比,将假阳性率降低了90%以上,同时正确识别了所有确诊的GA1个体。对资料的深入分析表明,特别是伴随高后续费用的假阳性结果可以显著减少。总之,了解NBS假阳性的起源,并实施数字层策略来提高GA1检测的特异性,可能会显著减轻新生儿及其家庭因NBS假阳性结果所带来的负担。
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引用次数: 0
Evaluation of Neonatal Screening Programs for Tyrosinemia Type 1 Worldwide. 评价新生儿筛查方案酪氨酸血症1型世界各地。
IF 4 Q1 GENETICS & HEREDITY Pub Date : 2024-12-16 DOI: 10.3390/ijns10040082
Allysa M Kuypers, Marelle J Bouva, J Gerard Loeber, Anita Boelen, Eugenie Dekkers, Konstantinos Petritis, C Austin Pickens, The Isns Representatives, Francjan J van Spronsen, M Rebecca Heiner-Fokkema

In The Netherlands, newborn screening (NBS) for tyrosinemia type 1 (TT1) uses dried blood spot (DBS) succinylacetone (SUAC) as a biomarker. However, high false-positive (FP) rates and a false-negative (FN) case show that the Dutch TT1 NBS protocol is suboptimal. In search of optimization options, we evaluated the protocols used by other NBS programs and their performance. We distributed an online survey to NBS program representatives worldwide (N = 41). Questions focused on the organization and performance of the programs and on changes since implementation. Thirty-three representatives completed the survey. TT1 incidence ranged from 1/13,636 to 1/750,000. Most NBS samples are taken between 36 and 72 h after birth. Most used biomarkers were DBS SUAC (78.9%), DBS Tyrosine (Tyr; 5.3%), or DBS Tyr with second tier SUAC (15.8%). The pooled median cut-off for SUAC was 1.50 µmol/L (range 0.3-7.0 µmol/L). The median cut-off from programs using laboratory-developed tests was significantly higher (2.63 µmol/L) than the medians from programs using commercial kits (range 1.0-1.7 µmol/L). The pooled median cut-off for Tyr was 216 µmol/L (range 120-600 µmol/L). Overall positive predictive values were 27.3% for SUAC, 1.2% for Tyr solely, and 90.1% for Tyr + SUAC. One FN result was reported for TT1 NBS using SUAC, while three FN results were reported for TT1 NBS using Tyr. The NBS programs for TT1 vary worldwide in terms of analytical methods, biochemical markers, and cut-off values. There is room for improvement through method standardization, cut-off adaptation, and integration of new biomarkers. Further enhancement is likely to be achieved by the application of post-analytical tools.

在荷兰,酪氨酸血症1型(TT1)的新生儿筛查(NBS)使用干血斑(DBS)琥珀酰丙酮(SUAC)作为生物标志物。然而,高假阳性(FP)率和假阴性(FN)病例表明荷兰TT1 NBS方案不是最佳方案。为了寻找优化方案,我们评估了其他NBS程序使用的协议及其性能。我们向世界各地的NBS项目代表(N = 41)分发了一份在线调查。问题集中在项目的组织和绩效以及实施后的变化。33名代表完成了调查。TT1发病率为1/13,636 ~ 1/750,000。大多数NBS样本是在出生后36至72小时之间采集的。使用最多的生物标志物是DBS SUAC(78.9%)、DBS酪氨酸(Tyr;5.3%),或DBS Tyr与二级SUAC(15.8%)。SUAC的中位截止值为1.50µmol/L(范围0.3-7.0µmol/L)。使用实验室开发的测试程序的中位数截止值(2.63µmol/L)明显高于使用商业试剂盒程序的中位数截止值(范围1.0-1.7µmol/L)。Tyr的中位截止值为216µmol/L(范围120-600µmol/L)。SUAC的总体阳性预测值为27.3%,Tyr单独为1.2%,Tyr + SUAC为90.1%。使用SUAC的TT1 NBS报告了一个FN结果,而使用Tyr的TT1 NBS报告了三个FN结果。国家统计局的TT1项目在世界范围内的分析方法、生化标记物和临界值各不相同。通过方法标准化、截断适应和新生物标志物的整合,还有改进的空间。应用后分析工具可能会进一步加强。
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引用次数: 0
N-Acetyltyrosine as a Biomarker of Parenteral Nutrition Administration in First-Tier Newborn Screening Assays. n -乙酰酪氨酸作为一级新生儿筛查中肠外营养管理的生物标志物。
IF 4 Q1 GENETICS & HEREDITY Pub Date : 2024-12-10 DOI: 10.3390/ijns10040081
C Austin Pickens, Samyukta Sah, Rahul Chandrappa, Samantha L Isenberg, Elya R Courtney, Timothy Lim, Donald H Chace, Rachel Lee, Carla Cuthbert, Konstantinos Petritis

Parenteral nutrition (PN) is a nutrient solution administered intravenously (IV) to premature babies. PN causes elevations of some amino acids in blood samples that are also biomarkers used in newborn screening (NBS). Therefore, PN status must be annotated by clinicians on dried blood spot (DBS) cards to reduce NBS laboratory burdens associated with potential false results; however, NBS laboratories continue to receive DBSs with misannotated PN status. N-acetyltyrosine (NAT), a water-soluble tyrosine analog used to increase tyrosine bioavailability in PN solutions, can be used as a blood-based biomarker of PN administration in NBS assays. Residual DBS specimens and manufactured DBSs were used in analyses. The assay was developed and validated using flow injection analysis tandem mass spectrometry (FIA-MS/MS) for the detection of NAT. NAT was only present in neonate DBSs with annotated PN administration and was multiplexed into first-tier newborn screening assays. NAT was highly correlated with amino acids present in PN solutions, such as arginine, leucine, methionine, phenylalanine, and valine. In our sample cohort, we determined an NAT cutoff could aid the identification of misannotated neonates administered PN. We also report the Amadori rearrangement product valine-hexose (Val-Hex) was quantifiable in neonates administered PN, which we suspect forms in the PN solution and/or IV lines. Here, we present the first known use of NAT as a biomarker of PN administration, which is currently being piloted by two U.S. NBS laboratories. NAT and Val-Hex can aid the identification of misannotated DBSs from neonates administered PN, thus decreasing false positive rates.

肠外营养(PN)是一种通过静脉(IV)给予早产儿的营养液。PN导致血液样本中一些氨基酸升高,这些氨基酸也是新生儿筛查(NBS)中使用的生物标志物。因此,临床医生必须在干血斑(DBS)卡上标注PN状态,以减少与潜在错误结果相关的NBS实验室负担;然而,NBS实验室继续收到带有错误PN状态注释的DBSs。n -乙酰基酪氨酸(NAT)是一种水溶性酪氨酸类似物,用于提高酪氨酸在PN溶液中的生物利用度,可作为NBS检测中PN给药的血液生物标志物。使用残余DBS标本和制造的DBS进行分析。采用流动注射分析串联质谱法(FIA-MS/MS)开发并验证了该检测方法,用于检测NAT。NAT仅存在于带有PN注释的新生儿DBSs中,并被复用到一级新生儿筛查分析中。NAT与PN溶液中存在的氨基酸高度相关,如精氨酸、亮氨酸、蛋氨酸、苯丙氨酸和缬氨酸。在我们的样本队列中,我们确定NAT切断可以帮助识别错误注释的给予PN的新生儿。我们还报道了Amadori重排产物缬氨酸-己糖(Val-Hex)在给予PN的新生儿中是可量化的,我们怀疑其形式存在于PN溶液和/或IV线中。在这里,我们提出了已知的第一个使用NAT作为PN给药的生物标志物,目前正在由两个美国NBS实验室进行试点。NAT和Val-Hex可以帮助识别给药的新生儿中错误注释的DBSs,从而降低假阳性率。
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引用次数: 0
Newborn Screening for Six Primary Conditions in a Clinical Setting in Morocco. 新生儿筛查的六个主要条件在摩洛哥临床设置。
IF 4 Q1 GENETICS & HEREDITY Pub Date : 2024-12-04 DOI: 10.3390/ijns10040080
Sara El Janahi, Mounir Filali, Zakia Boudar, Amina Akhattab, Rachid El Jaoudi, Najib Al Idrissi, Nouzha Dini, Chakib Nejjari, Raquel Yahyaoui, Michele A Lloyd-Puryear, Hassan Ghazal

Newborn screening (NBS) represents an important public health measure for the early detection of specified disorders; such screening can prevent disability and death, not only from metabolic disorders but also from endocrine, hematologic, immune, and cardiac disorders. Screening for critical congenital conditions affecting newborns' health is a great challenge, especially in developing countries such as Morocco, where NBS program infrastructure is lacking. In addition, the consanguinity rate is high in Morocco. This study aimed to demonstrate the feasibility of integrating NBS into a diagnostic laboratory for routine analysis. Six primary severe conditions were included: congenital hypothyroidism (CH), cystic fibrosis (CF), phenylketonuria (PKU), glucose-6-phosphate dehydrogenase deficiency (G6PD), congenital adrenal hyperplasia (CAH), and hemoglobinopathies.

Methods: A retrospective investigation was carried out to examine the outcomes of NBS in Casablanca, Morocco. A total of 5511 newborn blood samples were collected via heel-prick sampling and tested for the above disorders. Most of the samples were collected within the third and sixth days of birth. The dried blood spots were analyzed via a quantitative immunofluorescence technique and isoelectric focusing.

Results: A total of 72 newborns had one of the six pathological conditions. The most prevalent disorders were hemoglobinopathies, which were identified in 47 newborns (0.9%), with 29 having HbC carrier status (0.5%), 15 having Hb S carrier status (0.3%), and 3 having an Hb Bart's carrier profile (0.05%). This was followed by G6PD deficiency, which was found to affect 16 newborns (0.32% of cases). CF was found in one case (0.02%), whereas five newborns (0.09%) tested positive for CAH. Additionally, two newborns (0.04%) tested positive for CH, and one newborn tested positive for PKU (0.02%).

Conclusion: Our findings underscore the importance and success of NBS programs in preventing morbidity and mortality and improving the quality of life of affected neonates. The significant gap in data and research on these disorders within the Moroccan population highlights the urgent need to integrate NBS into routine practice in diagnostic laboratories across Morocco. This integration is crucial for enhancing the health and well-being of Moroccan newborns.

新生儿筛查(NBS)是早期发现特定疾病的一项重要公共卫生措施;这种筛查不仅可以预防代谢紊乱,还可以预防内分泌、血液、免疫和心脏紊乱造成的残疾和死亡。筛查影响新生儿健康的严重先天性疾病是一项巨大挑战,特别是在摩洛哥等发展中国家,那里缺乏国家统计局规划的基础设施。此外,摩洛哥的血亲率也很高。本研究旨在证明将NBS整合到诊断实验室进行常规分析的可行性。六种原发性严重疾病包括:先天性甲状腺功能减退症(CH)、囊性纤维化(CF)、苯丙酮尿症(PKU)、葡萄糖-6-磷酸脱氢酶缺乏症(G6PD)、先天性肾上腺增生症(CAH)和血红蛋白病。方法:对摩洛哥卡萨布兰卡市NBS患者进行回顾性调查。采用足跟穿刺法采集新生儿血样5511份,并对上述疾病进行检测。大多数样本是在出生后的第三天和第六天收集的。通过定量免疫荧光技术和等电聚焦技术分析干血斑。结果:共有72例新生儿出现6种病理条件中的一种。最普遍的疾病是血红蛋白病,在47名新生儿(0.9%)中发现,其中29名患有HbC携带者(0.5%),15名患有Hb S携带者(0.3%),3名患有Hb Bart携带者(0.05%)。其次是G6PD缺乏症,发现影响了16名新生儿(0.32%的病例)。CF 1例(0.02%),CAH 5例(0.09%)。此外,两名新生儿(0.04%)检测出CH阳性,一名新生儿检测出PKU阳性(0.02%)。结论:我们的研究结果强调了NBS计划在预防发病率和死亡率以及改善患病新生儿生活质量方面的重要性和成功。摩洛哥人口中关于这些疾病的数据和研究存在重大差距,这突出表明迫切需要将国家统计局纳入摩洛哥各地诊断实验室的常规实践。这种整合对于加强摩洛哥新生儿的健康和福祉至关重要。
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引用次数: 0
Newborn Screening for Acid Sphingomyelinase Deficiency: Prevalence and Genotypic Findings in Italy. 新生儿筛选酸性鞘磷脂酶缺乏症:患病率和基因型发现在意大利。
IF 4 Q1 GENETICS & HEREDITY Pub Date : 2024-12-04 DOI: 10.3390/ijns10040079
Vincenza Gragnaniello, Chiara Cazzorla, Daniela Gueraldi, Christian Loro, Elena Porcù, Leonardo Salviati, Alessandro P Burlina, Alberto B Burlina

Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder with a broad clinical spectrum. Early diagnosis and initiation of treatment are crucial for improving outcomes, yet the disease often goes undiagnosed due to its rarity and phenotypic heterogeneity. This study aims to evaluate the feasibility and disease incidence of newborn screening (NBS) for ASMD in Italy. Dried blood spot samples from 275,011 newborns were collected between 2015 and 2024 at the Regional Center for Expanded NBS in Padua. Acid sphingomyelinase activity was assayed using tandem mass spectrometry. Deidentified samples with reduced enzyme activity underwent second-tier testing with LysoSM quantification and SMPD1 gene analysis. Two samples were identified with reduced sphingomyelinase activity and elevated LysoSM levels. Both carried two SMPD1 variants, suggesting a diagnosis of ASMD. Molecular findings included novel and previously reported variants, some of uncertain significance. The overall incidence was 1 in 137,506 newborns and the PPV was 100%. This study demonstrates the feasibility of NBS for ASMD in Italy and provides evidence of a higher disease incidence than clinically reported, suggesting ASMD is an underdiagnosed condition. Optimized screening algorithms and second-tier biomarker testing can enhance the accuracy of NBS for ASMD. The long-term follow-up of identified cases is necessary for genotype-phenotype correlation and improving patient management.

酸性鞘磷脂酶缺乏症(ASMD)是一种罕见的溶酶体储存疾病,具有广泛的临床谱。早期诊断和开始治疗对于改善预后至关重要,但由于其罕见性和表型异质性,该病经常未被诊断。本研究旨在评估意大利新生儿ASMD筛查(NBS)的可行性和发病率。2015年至2024年间,在帕多瓦扩大国家统计局区域中心收集了275011名新生儿的干血斑样本。串联质谱法测定酸性鞘磷脂酶活性。对酶活性降低的去鉴定样品进行二级检测,包括LysoSM定量和SMPD1基因分析。两个样品被鉴定为鞘磷脂酶活性降低和溶酶sm水平升高。两人都携带两种SMPD1变异,提示ASMD的诊断。分子发现包括新的和以前报道的变异,一些不确定的意义。总发病率为1 / 137,506,PPV为100%。本研究证明了意大利NBS治疗ASMD的可行性,并提供了比临床报道更高的疾病发病率的证据,表明ASMD是一种未被诊断的疾病。优化筛选算法和二级生物标志物检测可提高NBS诊断ASMD的准确性。确定病例的长期随访对于基因型-表型相关性和改善患者管理是必要的。
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引用次数: 0
Newborn Genetic Screening Improves the Screening Efficiency for Congenital Hypothyroidism: A Prospective Multicenter Study in China. 新生儿遗传筛查提高先天性甲状腺功能减退症筛查效率:中国一项前瞻性多中心研究
IF 4 Q1 GENETICS & HEREDITY Pub Date : 2024-11-29 DOI: 10.3390/ijns10040078
Liang Ye, Yinhong Zhang, Jizhen Feng, Cidan Huang, Xiaohua Wang, Lianshu Han, Yonglan Huang, Hui Zou, Baosheng Zhu, Jingkun Miao

Newborn congenital hypothyroidism (CH) screening has been widely used worldwide. The objective of this study was to evaluate the effectiveness of applying biochemical and gene panel sequencing as screening tests for CH and to analyze the mutation spectrum of CH in China. Newborns were prospectively recruited from eight hospitals in China between February and December 2021. Clinical characteristics were collected. Second-generation sequencing was used to detect four CH-related genes, and the genetic patterns of the pathogenic genes were analyzed. We analyzed the relationship between genotype and biochemical phenotype. A total of 29,601 newborns were screened for CH. Gene panel sequencing identified 18 patients, including 10 patients affected by biochemically and genetically screened disorders and 8 patients affected by solely genetically screened disorders. The predictive positive value of genetic screening was 34.62%, which was much greater than that of biochemical screening alone (17.99%). A total of 94 cases of congenital thyroid dysfunction were confirmed by biochemical and genetic screening, including 30 CHs and 64 isolated hyperthyrotropinemia (HTT), with an incidence of 1/987 for CH and 1/463 for HTT, and a total incidence of 1/315 for hypothyroidism. The incidence rate and number of patients in Jinan were the highest, and the incidence rates in Shijiazhuang and Shanghai were the lowest. The gene mutation rate in this study was 19.1%, mainly DUOX2 mutation. The most common variant of DUOX2 was c.1588A>T(p.Lys530*). There was only a difference in sFT4 between groups with gene mutations and those without mutations. Genetic screening is a supplement to biochemical screening. Combining biochemical screening with genetic screening is useful for improving screening efficiency. The incidence of CH in China according to a multicenter study of nearly 30,000 NBS surveys was 1/315. DUOX2 gene mutations are commonly detected in these patients.

新生儿先天性甲状腺功能减退症(CH)筛查已在世界范围内得到广泛应用。本研究的目的是评估应用生化和基因面板测序作为筛查CH的有效性,并分析中国CH的突变谱。在2021年2月至12月期间,从中国的八家医院前瞻性地招募了新生儿。收集临床特征。采用二代测序法检测4个ch相关基因,分析致病基因的遗传模式。我们分析了基因型与生化表型的关系。共有29601名新生儿进行了CH筛查。基因面板测序确定了18名患者,其中10名患者患有生化和遗传筛查的疾病,8名患者患有单纯遗传筛查的疾病。遗传筛查的预测阳性率为34.62%,远高于单纯生化筛查的预测阳性率(17.99%)。经生化及遗传筛查共确诊先天性甲状腺功能障碍94例,其中CHs 30例,孤立性高甲状腺素血症(HTT) 64例,CH发病率为1/987,HTT发病率为1/463,甲状腺功能减退总发病率为1/315。济南的发病率和发病人数最高,石家庄和上海的发病率最低。本研究基因突变率为19.1%,以DUOX2突变为主。DUOX2最常见的变异是c.1588A >t (p.Lys530*)。基因突变组与非基因突变组之间仅存在sFT4的差异。遗传筛查是对生化筛查的补充。生化筛选与遗传筛选相结合有助于提高筛选效率。根据国家统计局近3万份调查的多中心研究,中国CH的发病率为1/315。在这些患者中通常检测到DUOX2基因突变。
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引用次数: 0
期刊
International Journal of Neonatal Screening
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