背景:MACF1基因,在染色体1p34.3上发现,对于控制细胞骨架动力学至关重要,细胞运动,增长,和差异化。它由101个外显子组成,跨度超过270kb。16p13.11微重复综合征是由16p13.11染色体拷贝的重复引起的,并与各种神经发育和生理异常有关。MACF1和16p13.11微重复对神经发育都有显著影响,可能导致神经损伤或神经系统疾病。这项研究提出了一个独特的病例,患者同时经历了从头MACF1突变和遗传性16p13.11微重复,以前没有报道过。
方法:在本报告中,我们描述了一个中国早产新生儿,表现出16.13.11微重复综合征的典型特征。这些特征包括发育迟缓,呼吸问题,喂养问题,肌肉无力,关节过度运动,和多种先天性异常。通过全外显子组测序,我们在MACF1基因中发现了一个致病突变(c.15266T>C/p.Met5089Thr)。此外,微阵列分析后,我们证实存在16p13.11微重复(chr16:14,916,289-16,315,688),是从母亲那里继承的。
结论:患者的临床表现,以肌肉无力和多重出生缺陷为特征,可能归因于从头MACF1突变和16p13.11重复,这可能会进一步加剧她的严重症状。对具有复杂临床表现的个体进行基因检测可以为诊断提供有价值的见解,并为患者及其家人的遗传咨询提供参考。
BACKGROUND: The MACF1 gene, found on chromosome 1p34.3, is vital for controlling cytoskeleton dynamics, cell movement, growth, and differentiation. It consists of 101 exons, spanning over 270 kb. The 16p13.11 microduplication syndrome results from the duplication of 16p13.11 chromosome copies and is associated with various neurodevelopmental and physiological abnormalities. Both MACF1 and 16p13.11 microduplication have significant impacts on neural development, potentially leading to nerve damage or neurological diseases. This study presents a unique case of a patient simultaneously experiencing a de novo MACF1 mutation and a hereditary 16p13.11 microduplication, which has not been reported previously.
METHODS: In this report, we describe a Chinese preterm newborn girl exhibiting the typical characteristics of 16.13.11 microduplication syndrome. These features include developmental delay, respiratory issues, feeding problems, muscle weakness, excessive joint movement, and multiple congenital abnormalities. Through whole-exome sequencing, we identified a disease-causing mutation in the MACF1 gene (c.15266T > C / p. Met5089Thr). Additionally, after microarray analysis, we confirmed the presence of a 16p13.11 microduplication (chr16:14,916,289 - 16,315,688), which was inherited from the mother.
CONCLUSIONS: The patient\'s clinical presentation, marked by muscle weakness and multiple birth defects, may be attributed to both the de novo MACF1 mutation and the 16p13.11 duplication, which could have further amplified her severe symptoms. Genetic testing for individuals with complex clinical manifestations can offer valuable insights for diagnosis and serve as a reference for genetic counseling for both patients and their families.