Impact of Deletion on Angelman Syndrome Phenotype Variability: Phenotype-Genotype Correlation in 97 Patients with Motor Developmental Delay.

IF 0.4 Q4 PEDIATRICS
Journal of pediatric genetics Pub Date : 2022-08-16 eCollection Date: 2024-03-01 DOI:10.1055/s-0042-1751268
Hanae Daha Belghiti, Meriame Abbassi, Hanane Sayel, Mohamed Ahakoud, Badr Eddine El Makhzen, Norman Lee, Silvia Russo, Sana Chaouki, Laila Bouguenouch
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引用次数: 0

Abstract

Angelman syndrome (AS) is a rare neurodevelopmental disorder due to genetic defects involving chromosome 15, known by intellectual disability, cognitive and behavioral disorders, ataxia, delayed motor development, and seizures. This study highlights the clinical spectrum and molecular research to establish the genotype-phenotype correlation in the pediatric Moroccan population. Methylation-specific-polymerase chain reaction (MS-PCR) is a primordial technique not only to identify the genetic mechanism of AS but also to characterize the different molecular classes induced in the appearance of the clinical symptoms. Patients with positive methylation profile were additionally studied by fluorescent in situ hybridization. Sequencing analysis of the UBE3A gene was performed for patients with negative MS-PCR. We used Fisher's test to assess differences in the distribution of features frequencies among the deletional and the nondeletional group. Statistical analysis was performed using R project. We identified from 97 patients diagnosed with AS, 14 (2.06%) had a classical AS phenotype, while 70 (84.5%) patients displayed a subset of consistent and frequent criteria. Development delay was shown severe in 63% and moderate in 37%. Nineteen out of 97 of them had MS-PCR positive in which 17 (89.47%) had 15q11-q13 deletion. Deletion patients presented a higher incidence of epileptic seizures ( p  = 0.04), ataxia ( p  = 0.0008), and abnormal electroencephalogram (EEG) profile ( p  = 0.003). We further found out a frameshift deletion located at exon 9 of the UBE3A gene discovered in a 5 years old patient. We report in this study the genotype-phenotype correlation using different molecular testing. Correlation analysis did not reveal any statistical differences in phenotypic dissimilarity between deletion and nondeletion groups for most clinical features, except the correlation was highly significant in the abnormal EEG. According to our findings, we recommend offering MS-PCR analysis to all patients with severe intellectual disability, developmental delay, speech impairment, happy demeanor, and hypopigmentation.

基因缺失对安吉尔曼综合征表型变异的影响:97例运动发育迟缓患者的表型-基因型相关性。
安杰尔曼综合征(AS)是一种罕见的神经发育障碍性疾病,由涉及 15 号染色体的遗传缺陷引起,以智力障碍、认知和行为障碍、共济失调、运动发育迟缓和癫痫发作而闻名。本研究强调了摩洛哥儿科人群的临床谱系和分子研究,以确定基因型与表型之间的相关性。甲基化特异性聚合酶链反应(MS-PCR)是一项基本技术,不仅能确定强直性脊柱炎的遗传机制,还能描述临床症状出现时诱发的不同分子类别。此外,还通过荧光原位杂交对甲基化谱呈阳性的患者进行了研究。对 MS-PCR 阴性的患者进行了 UBE3A 基因测序分析。我们使用费雪检验来评估缺失组和非缺失组之间特征频率分布的差异。统计分析使用 R 项目进行。我们从97名确诊为强直性脊柱炎的患者中发现,14名患者(2.06%)具有典型的强直性脊柱炎表型,而70名患者(84.5%)则显示了一组一致的常见标准。63%的患者表现为严重发育迟缓,37%为中度发育迟缓。97 例患者中有 19 例 MS-PCR 阳性,其中 17 例(89.47%)有 15q11-q13 缺失。缺失患者癫痫发作(p = 0.04)、共济失调(p = 0.0008)和脑电图(EEG)异常(p = 0.003)的发生率较高。我们还在一名 5 岁患者身上发现了 UBE3A 基因外显子 9 的缺失。我们在本研究中报告了使用不同分子检测方法的基因型与表型之间的相关性。相关性分析表明,在大多数临床特征方面,缺失组和非缺失组的表型差异没有统计学差异,但在异常脑电图方面相关性非常显著。根据我们的研究结果,我们建议对所有有严重智力障碍、发育迟缓、语言障碍、性格开朗和色素沉着的患者进行 MS-PCR 分析。
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来源期刊
自引率
0.00%
发文量
32
期刊介绍: The Journal of Pediatric Genetics is an English multidisciplinary peer-reviewed international journal publishing articles on all aspects of genetics in childhood and of the genetics of experimental models. These topics include clinical genetics, molecular genetics, biochemical genetics, medical genetics, dysmorphology, teratology, genetic counselling, genetic engineering, formal genetics, neuropsychiatric genetics, behavioral genetics, community genetics, cytogenetics, hereditary or syndromic cancer genetics, genetic mapping, reproductive genetics, fetal pathology and prenatal diagnosis, multiple congenital anomaly syndromes, and molecular embryology of birth defects. Journal of Pediatric Genetics provides an in-depth update on new subjects and current comprehensive coverage of the latest techniques used in the diagnosis of childhood genetics. Journal of Pediatric Genetics encourages submissions from all authors throughout the world. The following articles will be considered for publication: editorials, original and review articles, short report, rapid communications, case reports, letters to the editor, and book reviews. The aim of the journal is to share and disseminate knowledge between all disciplines in the field of pediatric genetics. This journal is a publication of the World Pediatric Society: http://www.worldpediatricsociety.org/ The Journal of Pediatric Genetics is available in print and online. Articles published ahead of print are available via the eFirst service on the Thieme E-Journals platform.
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