Department of Basic Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia.
Department of Internal Medicine, College of Medicine, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia.
Hum Genomics. 2024 Sep 4;18(1):95. doi: 10.1186/s40246-024-00662-0.
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.
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.
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 缺失和重复被发现是临床表型提示染色体综合征的病例中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，表现从正常发育和认知到严重表型的变化范围很广。临床表现从神经认知和全面发育迟缓 (GDD)、智力障碍和语言缺陷（构音障碍/运动障碍）到神经精神和自闭症谱系障碍。其他表现包括发育不良特征、先天性畸形、胰岛素抵抗和肥胖倾向。我们的研究旨在缩小沙特阿拉伯和中东及北非 (MENA) 地区在遗传疾病方面的知识差距，特别是与 CNV 相关的疾病。尽管这些疾病很少见，但 MENA 地区的遗传研究显示出很高的潜力，具有显著的遗传和表型新颖性。
我们通过微阵列（arr[GRCh38]16p11.2(29555974_30166595)x1）[arr[GRCh37]16p11.2(29567295_30177916)x1)]发现并确认了杂合性新生近端染色体 16p11.2 微缺失，通过全外显子测序（arr[GRCh37]16p11.2(29635211_30199850)x1）。我们报告了一名患有严重运动和认知障碍、肌阵挛性癫痫、耳聋和视力障碍的沙特女孩，她携带上述缺失。我们的研究扩大了与近端 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、视神经萎缩和扁平视网膜。值得注意的是，患者表现出罕见的小头畸形、与 Dandy-Walker 谱系一致的特征以及薄胼胝体（TCC），这在患有 16p11.2 微缺失的患者中极为罕见。此外，患者还表现出皮肤和毛发色素减退区域，这归因于 TYR 基因中的纯合功能丧失等位基因。
本报告扩展了与近端 16p11.2 微缺失综合征相关的临床表型，强调了遗传研究在沙特阿拉伯和 MENA 地区的潜力。它强调了未来进行类似研究的重要性。
