PDF(Pubmed)
Abstract：
BACKGROUND: Trisomy 20p is a rare genetic condition caused by a duplication of the short arm of chromosome 20.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：20p三体是一种罕见的遗传病，由20号染色体短臂的重复引起。
方法：我们采用临床观察和分子遗传学检测（SNP微阵列），研究患有未知畸形综合征的同卵双胞胎男性。我们对20p三体进行了文献综述，并整理了自2000年以来报告的20名受影响受试者的临床和分子遗传学发现。
结果：相同的双胞胎男性，他们的产前过程因双胞胎对双胞胎输血而变得复杂，在2岁时评估时，表现出深刻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，没有其他染色体畸变。对20p三体综合征的文献调查确定了自2000年以来报道的其他20例这种情况，我们将其与Sidwell等人总结的33例进行了比较。(2000)。在总共55名受影响的个人中，我们发现了一种独特的临床表型，可以洞悉20p13基因异常剂量的影响。这些基因座包括FAM110A(OMIM611393),ANGPT4(OMIM603705),RSPO4(OMIM610573),PSMF1(OMIM617858),SNPH(OMIM604942),SDCBP2(OMIM617358),FKBP1A(OMIM186945),TMEM74B,C20orf202和RAD21L1(OMIM619533)。基因分析强调syntaphilin（SNPH）在哺乳动物大脑中高表达，它被认为是神经元轴突线粒体运输的关键，并直接影响轴突形态发生和功能。
结论：我们认为三体性引起的syntaphilin异常活动是语言的主要原因，神经认知，和20p三体个体报告的总运动延迟。其他研究,例如,从受影响的患者产生的脑器官的表征可能有助于更好地了解这种情况，并可能提出合理的补救措施，以改善受影响的个人及其家人的生活。
方法：我们采用临床观察和分子遗传学检测（SNP微阵列），研究患有未知畸形综合征的同卵双胞胎男性。我们对20p三体进行了文献综述，并整理了自2000年以来报告的20名受影响受试者的临床和分子遗传学发现。
结果：相同的双胞胎男性，他们的产前过程因双胞胎对双胞胎输血而变得复杂，在2岁时评估时，表现出深刻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，没有其他染色体畸变。对20p三体综合征的文献调查确定了自2000年以来报道的其他20例这种情况，我们将其与Sidwell等人总结的33例进行了比较。(2000)。在总共55名受影响的个人中，我们发现了一种独特的临床表型，可以洞悉20p13基因异常剂量的影响。这些基因座包括FAM110A(OMIM611393),ANGPT4(OMIM603705),RSPO4(OMIM610573),PSMF1(OMIM617858),SNPH(OMIM604942),SDCBP2(OMIM617358),FKBP1A(OMIM186945),TMEM74B,C20orf202和RAD21L1(OMIM619533)。基因分析强调syntaphilin（SNPH）在哺乳动物大脑中高表达，它被认为是神经元轴突线粒体运输的关键，并直接影响轴突形态发生和功能。
结论：我们认为三体性引起的syntaphilin异常活动是语言的主要原因，神经认知，和20p三体个体报告的总运动延迟。其他研究,例如,从受影响的患者产生的脑器官的表征可能有助于更好地了解这种情况，并可能提出合理的补救措施，以改善受影响的个人及其家人的生活。
