Chromosome 16p11.2 microdeletion syndrome with microcephaly and Dandy-Walker malformation spectrum: expanding the known phenotype.

IF 3.8 3区 医学 Q2 GENETICS & HEREDITY
Liena Elbaghir Omer Elsayed, Norah Ayed AlHarbi, Ashwaq Mohammed Alqarni, Huda Hussein Elwasila Eltayeb, Noura Mostafa Mohamed Mostafa, Maha Mohammed Abdulrahim, Hadeel Ibrahim Bin Zaid, Latifah Mansour Alanzi, Sarah Abdullah Ababtain, Khawlah Aldulaijan, Sheka Yagub Aloyouni, Moneeb Abdullah Kassem Othman, Mohammad Abdullah Alkheilewi, Adel Mohammed Binduraihem, Hadeel Abdollah Alrukban, Hiba Yousif Ahmed, Faten Abdullah AlRadini, Hadil Mohammad Alahdal, Aziza Mufareh Mushiba, Omaima Abdulazeem Alzaher
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引用次数: 0

Abstract

Background: Chromosome 16p11.2 deletions and duplications were found to be the second most common copy number variation (CNV) reported in cases with clinical presentation suggestive of chromosomal syndromes. Chromosome 16p11.2 deletion syndrome shows remarkable phenotypic heterogeneity with a wide variability of presentation extending from normal development and cognition to severe phenotypes. The clinical spectrum ranges from neurocognitive and global developmental delay (GDD), intellectual disability, and language defects (dysarthria /apraxia) to neuropsychiatric and autism spectrum disorders. Other presentations include dysmorphic features, congenital malformations, insulin resistance, and a tendency for obesity. Our study aims to narrow the gap of knowledge in Saudi Arabia and the Middle Eastern and Northern African (MENA) region about genetic disorders, particularly CNV-associated disorders. Despite their rarity, genetic studies in the MENA region revealed high potential with remarkable genetic and phenotypic novelty.

Results: We identified a heterozygous de novo recurrent proximal chromosome 16p11.2 microdeletion by microarray (arr[GRCh38]16p11.2(29555974_30166595)x1) [(arr[GRCh37]16p11.2(29567295_30177916)x1)] and confirmed by whole exome sequencing (arr[GRCh37]16p11.2(29635211_30199850)x1). We report a Saudi girl with severe motor and cognitive disability, myoclonic epilepsy, deafness, and visual impairment carrying the above-described deletion. Our study broadens the known phenotypic spectrum associated with recurrent proximal 16p11.2 microdeletion syndrome to include developmental dysplasia of the hip, optic atrophy, and a flat retina. Notably, the patient exhibited a rare combination of microcephaly, features consistent with the Dandy-Walker spectrum, and a thin corpus callosum (TCC), which are extremely infrequent presentations in patients with the 16p11.2 microdeletion. Additionally, the patient displayed areas of skin and hair hypopigmentation, attributed to a homozygous hypomorphic allele in the TYR gene.

Conclusion: This report expands on the clinical phenotype associated with proximal 16p11.2 microdeletion syndrome, highlighting the potential of genetic research in Saudi Arabia and the MENA region. It underscores the importance of similar future studies.

染色体 16p11.2 微缺失综合征伴小头畸形和 Dandy-Walker 畸形谱系:扩展已知表型。
背景:研究发现,在临床表现提示染色体综合征的病例中,染色体 16p11.2 缺失和重复是第二常见的拷贝数变异(CNV)。染色体 16p11.2 缺失综合征表现出显著的表型异质性,从正常发育和认知能力到严重表型,表现形式差异很大。临床表现范围从神经认知和全面发育迟缓(GDD)、智力障碍、语言缺陷(构音障碍/语障)到神经精神障碍和自闭症谱系障碍。其他表现还包括畸形特征、先天畸形、胰岛素抵抗和肥胖倾向。我们的研究旨在缩小沙特阿拉伯及中东和北非地区对遗传性疾病,尤其是 CNV 相关疾病的认识差距。尽管罕见,但中东和北非地区的遗传研究揭示了遗传和表型新颖的巨大潜力:结果:我们通过微阵列(arr[GRCh38]16p11.2(29555974_30166595)x1)[(arr[GRCh37]16p11.2(29567295_30177916)x1)]发现了一个杂合的新发复发性近端染色体 16p11.2 微缺失,并通过全外显子组测序(arr[GRCh37]16p11.2(29635211_30199850)x1)得到证实。我们报告了一名患有严重运动和认知障碍、肌阵挛癫痫、耳聋和视力障碍的沙特女孩,她携带上述缺失。我们的研究拓宽了与复发性近端 16p11.2 微缺失综合征相关的已知表型谱,包括髋关节发育不良、视神经萎缩和视网膜扁平。值得注意的是,该患者表现出罕见的小头畸形、与丹迪-沃克谱系一致的特征和薄胼胝体(TCC),这在 16p11.2 微缺失患者中极为罕见。此外,该患者的皮肤和毛发有色素沉着区,这归因于 TYR 基因中的同卵低效等位基因:本报告扩展了与近端 16p11.2 微缺失综合征相关的临床表型,凸显了沙特阿拉伯和中东及北非地区基因研究的潜力。它强调了未来类似研究的重要性。
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来源期刊
Human Genomics
Human Genomics GENETICS & HEREDITY-
CiteScore
6.00
自引率
2.20%
发文量
55
审稿时长
11 weeks
期刊介绍: Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.
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