3q29重复综合征的遗传结构与临床多态性解析：文献综述及两例单基因BDH1重复新病例报告
Delineation of the Genetic Architecture and Clinical Polymorphism of 3q29 Duplication Syndrome: A Review of the Literature and a Report of Two Novel Patients With Single-Gene BDH1 Duplications.
作者信息
Kashevarova A A, Lopatkina M E, Vasilyeva O Yu, Fedotov D A, Lobanov A D, Fonova E A, Zhalsanova I Z, Zarubin A A, Salyukova O A, Belyaeva E O, Petrova V V, Ravzhaeva E G, Agafonova A A, Cheremnykh A D, Torkhova N B, Vovk S L, Lebedev I N
机构信息
Laboratory of Cytogenetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.
Laboratory of Ontogenetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.
出版信息
Mol Genet Genomic Med. 2025 Jan;13(1):e70047. doi: 10.1002/mgg3.70047.
BACKGROUND
Chromosome 3q29 duplication syndrome is a rare chromosomal disorder with a frequency of 1:5000 in patients with a neurodevelopmental phenotype. The syndrome is characterized by phenotypic polymorphism and reduced penetrance.
METHODS
Patients were investigated by performing a cytogenetic analysis of GTG-banded metaphases, aCGH with the SurePrint G3 Human CGH Microarray 8×60K, qPCR, FISH, and WES.
RESULTS
Here, we report five new patients with atypical duplications overlapping with the 3q29 duplication syndrome region and no other genetic findings. In two patients, duplications were found in the single BDH1 gene, a candidate gene for the 3q29 duplication phenotype. For the first time, we delineated and described the smallest minimal critical region, including the single BDH1 gene; in our patients, this region was associated with ASD, heart defects, biliary tract dysfunction, and obesity. The frequencies of the pathological phenotypes in duplication carriers reported in the literature were calculated and compared with those in patients with 3q29 deletions. Most of the phenotypes were observed in both groups but were significantly less common among individuals with 3q29 duplications. Mirrored phenotypes in patients with duplications and deletions included overweight and weight deficit. Schizophrenia, generalized anxiety disorder, and recurrent ear infections were unique phenotypes of patients carrying deletions.
CONCLUSION
Chromosome 3q29 duplication syndrome is characterized by a complex genetic architecture and clinical polymorphism.
背景
3q29染色体重复综合征是一种罕见的染色体疾病，在具有神经发育表型的患者中发生率为1:5000。该综合征的特征是表型多态性和外显率降低。
方法
通过对GTG带型中期染色体进行细胞遗传学分析、使用SurePrint G3人类比较基因组杂交微阵列8×60K进行aCGH、定量聚合酶链反应（qPCR）、荧光原位杂交（FISH）和全外显子测序（WES）对患者进行研究。
结果
在此，我们报告了5例新患者，其非典型重复与3q29重复综合征区域重叠，且无其他遗传发现。在2例患者中，在单个BDH1基因中发现了重复，该基因是3q29重复表型的候选基因。我们首次划定并描述了最小的关键区域，包括单个BDH1基因；在我们的患者中，该区域与自闭症谱系障碍（ASD）、心脏缺陷、胆道功能障碍和肥胖有关。计算了文献中报道的重复携带者的病理表型频率，并与3q29缺失患者的频率进行了比较。大多数表型在两组中均有观察到，但在3q29重复的个体中明显较少见。重复和缺失患者中的镜像表型包括超重和体重不足。精神分裂症、广泛性焦虑症和复发性耳部感染是携带缺失患者的独特表型。
结论
3q29染色体重复综合征的特征是复杂的遗传结构和临床多态性。
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