Ding Qiliang, Stander Zinandre, Elizalde Brandon J, Stelmach Erica S, Duncan Jaime C, Vidal-Folch Noemi, Hasadsri Linda, Rumilla Kandelaria M, Shen Wei
Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
Division of Genetics, Genomics and Metabolism, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, 60611, USA.
Clin Epigenetics. 2025 Apr 29;17(1):67. doi: 10.1186/s13148-025-01873-5.
Most Beckwith-Wiedemann syndrome (BWS) cases are sporadic; nonetheless, imprinting center 1 (IC1) microdeletions have been suggested as a rare cause of familial BWS, with ~ 20 reported cases. We report 13 cases from nine families with IC1 microdeletions. Recurrent 1.4-kb, 1.8-kb, and 2.2-kb deletions were observed. IC1 hypermethylation was identified in all families, and we established a statistically significant relationship between IC1 microdeletions and hypermethylation (OR: 108.17, p = 2.76e-13). This study confirms IC1 microdeletions as a cause of familial BWS, expands the understanding of their molecular mechanisms, and supports a Likely Pathogenic clinical classification for IC1 microdeletions.
大多数贝克威思-维德曼综合征（BWS）病例为散发性；尽管如此，印记中心1（IC1）微缺失被认为是家族性BWS的罕见病因，据报道约有20例。我们报告了来自9个家族的13例IC1微缺失病例。观察到反复出现的1.4kb、1.8kb和2.2kb缺失。在所有家族中均鉴定出IC1高甲基化，并且我们建立了IC1微缺失与高甲基化之间具有统计学意义的关系（比值比：108.17，p = 2.76×10⁻¹³）。本研究证实IC1微缺失是家族性BWS的病因，扩展了对其分子机制的理解，并支持将IC1微缺失分类为可能致病的临床分类。
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