Center for Gene Therapy, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, USA.
Division of Genetic and Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.
Mol Genet Genomic Med. 2024 May;12(5):e2436. doi: 10.1002/mgg3.2436.
Trisomy 20p is a rare genetic condition caused by a duplication of the short arm of chromosome 20.
We employed clinical observation and molecular genetic testing (SNP microarray), to study identical twin males with an unknown dysmorphic syndrome. We conducted a literature review of trisomy 20p and collated the clinical and molecular genetic findings on 20 affected subjects reported since 2000.
Identical twin males, whose prenatal course was complicated by a twin-to-twin transfusion, manifested profound language and neurocognitive delays as well as distinctive facial dysmorphisms when evaluated at 2 years of age. SNP microarray identified identical duplications of 20p13 with no other chromosomal aberrations. A literature survey of 20p trisomy syndrome identified 20 other examples of this condition reported since 2000, which we collated with 33 summarized by Sidwell et al. (2000). Within the combined total of 55 affected individuals, we found a distinctive clinical phenotype that provides insight on the effects of abnormal dosage of genes in 20p13. These loci include FAM110A (OMIM 611393), ANGPT4 (OMIM 603705), RSPO4 (OMIM 610573), PSMF1 (OMIM 617858), SNPH (OMIM 604942), SDCBP2 (OMIM 617358), FKBP1A (OMIM 186945), TMEM74B, C20orf202, and RAD21L1 (OMIM 619533). Gene profiling highlighted that syntaphilin (SNPH) is highly expressed in mammalian brain, where it is considered critical for mitochondrial transport in neuronal axons, and to directly influence axonal morphogenesis and function.
We propose that abnormal activity of syntaphilin engendered by the trisomy is primarily responsible for the language, neurocognitive, and gross motor delays reported in individuals with 20p trisomy. Additional studies, for example, characterization of cerebral organoids generated from affected patients may help to better understand this condition, and potentially suggest rational remedies to improve the lives of affected individuals and their families.
20 号染色体短臂三体综合征是一种由 20 号染色体短臂重复引起的罕见遗传病症。
我们采用临床观察和分子遗传学检测（SNP 微阵列）的方法，研究了一对患有不明畸形综合征的同卵双胞胎男性。我们对 2000 年以来报道的 20 例 20p 三体综合征患者的临床和分子遗传学资料进行了综述。
这对男性双胞胎，其产前过程因双胎输血而复杂化，在 2 岁时评估时表现出严重的语言和神经认知延迟以及独特的面部畸形。SNP 微阵列鉴定出 20p13 的相同重复，没有其他染色体异常。对 20p 三体综合征的文献调查发现，自 2000 年以来，有 20 例其他病例报道，我们将其与 Sidwell 等人（2000 年）综述的 33 例病例进行了汇总。在 55 名受影响的个体中，我们发现了一种独特的临床表型，这为了解 20p13 基因异常剂量的影响提供了线索。这些基因座包括 FAM110A（OMIM 611393）、ANGPT4（OMIM 603705）、RSPO4（OMIM 610573）、PSMF1（OMIM 617858）、SNPH（OMIM 604942）、SDCBP2（OMIM 617358）、FKBP1A（OMIM 186945）、TMEM74B、C20orf202 和 RAD21L1（OMIM 619533）。基因谱分析突出表明，突触磷（SNPH）在哺乳动物大脑中高度表达，被认为对神经元轴突中线粒体运输至关重要，并直接影响轴突形态发生和功能。
我们提出，20p 三体综合征中突触磷的异常活性可能是导致患者语言、神经认知和大运动发育迟缓的主要原因。进一步的研究，例如，对受影响患者的大脑类器官的特征进行描述，可能有助于更好地理解这种疾病，并可能提出合理的治疗方法，以改善受影响个体及其家庭的生活。
