一个16p11.2微重复综合征家系的临床与遗传学分析及多系统表现异质性
Clinical and genetic analysis of a family with 16p11.2 microduplication syndrome and variable multisystem manifestations.
文献信息
| PMID | 42727732 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Hai-Lun Huang |
| 作者单位 | Department of Traditional Chinese Medicine and Neurology and Nephrology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China; Department of Hematology and Thoracic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China. |
| 期刊 | Gene |
| SCI 分区 | Q2 |
| IF | 2.9 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 耳科 |
中文摘要
背景： 16p11.2微重复综合征（OMIM #614671）是16p11.2位点上一种致病性复发性拷贝数增加，与神经发育、生长及医学表型的可变表现度相关。携带者队列中已有胃肠道症状的报道，但关于胃肠动力及神经肌肉表现的详细记录仍然有限。方法：我们对一个多代家系进行了临床与遗传学分析，该家系先证者（III1）表现为肢体肌肉疼痛、运动不耐受及慢性胃肠道症状。通过下一代测序（NGS）、基于低通量全基因组测序（lpWGS）的CNV分析、Sanger测序及qPCR验证，鉴定出16p11.2（BP4-BP5）处一个0.8 Mb的微重复，涉及包括TBX6在内的44个基因，遗传自母亲（II2）。结果：先证者的临床表现包括发育迟缓、尖下巴、低体重指数、胃肠功能障碍（慢性腹痛、腹泻、食管动力障碍及直肠脱垂）、前倾步态、轻度脊柱侧弯以及伴炎症性肌肉受累的肢体肌肉萎缩。四名家庭成员（II2、III1、III2和III4）携带该微重复，但其可获得的临床特征在严重程度及受累系统方面存在差异。先证者的双胞胎兄弟（III2）有左耳耳聋和癫痫，个体II2因视锥-视杆细胞营养不良而失明，III4则表现出更明显的脊柱侧弯。结论：该家系提供了16p11.2微重复携带者以显著胃肠动力及神经肌肉表现为特征的详细临床与遗传学描述，从而丰富了这一复发性CNV的临床特征，并支持显著的家系内表型异质性。
英文摘要
16p11.2 microduplication syndrome (OMIM #614671) is a pathogenic recurrent copy-number gain at the 16p11.2 locus and is associated with variable expressivity across neurodevelopmental, growth, and medical phenotypes. Gastrointestinal symptoms have been reported in carrier cohorts, but detailed documentation of gastrointestinal motility and neuromuscular findings remains limited. We performed clinical and genetic analyses in a multigenerational family in which the proband (III1) presented with limb muscle pain, exercise intolerance, and chronic gastrointestinal symptoms. Next-generation sequencing (NGS), low-pass whole-genome sequencing (lpWGS)-based CNV analysis, Sanger sequencing, and qPCR validation identified a 0.8 Mb microduplication at 16p11.2 (BP4-BP5), involving 44 genes including TBX6, inherited from the mother (II2). The proband's clinical manifestations included developmental delay, pointed chin, low body mass index, gastrointestinal dysfunction (chronic abdominal pain, diarrhea, esophageal motility disorder, and rectal prolapse), forward-leaning gait, mild scoliosis, and limb muscle atrophy with inflammatory muscle involvement. Four family members (II2, III1, III2, and III4) carried the microduplication, but their available clinical features varied in severity and system involvement. The proband's twin brother (III2) had left ear deafness and epilepsy, individual II2 had blindness from cone-rod dystrophy, and III4 showed more pronounced scoliosis. This family provides a detailed clinical and genetic description of 16p11.2 microduplication carriers with prominent gastrointestinal motility and neuromuscular manifestations, thereby enriching the clinical characterization of this recurrent CNV and supporting substantial intrafamilial phenotypic heterogeneity.