Department of the Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, ENT Institute and Otorhinolaryngology, Fudan University, Shanghai, 200031, China.
NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, 200031, China.
BMC Med Genomics. 2024 Oct 18;17(1):254. doi: 10.1186/s12920-024-02023-1.
Over 700 syndromes associated with hearing loss (HL) have been identified. Labyrinthine aplasia, microtia, and microdontia (LAMM syndrome, OMIM: 610706) is a rare HL syndrome characterized by congenital sensorineural HL, labyrinthine aplasia, type I microtia and microdontia, which is caused by biallelic variants in the FGF3 gene. Using Whole-exome sequencing (WES), we identified a novel missense FGF3 variant (c.137G > C, p. Arg46Pro (NM_005247.4) in three unrelated Uyghur ethnic families. This variant is classified as a variant of uncertain significance according to ACMG guidelines, with the applied criteria of PM3, PM2_Supporting, PP3 and PP4. Patients from the three families revealed variable clinical features. We found a novel phenotype, sparse hair, in one of the proband. Our findings expanded the variant and phenotype spectrum of LAMM syndrome and provided new insights to the diagnose and pathogenesis investigation of the disease.
已经发现了 700 多种与听力损失（HL）相关的综合征。内耳发育不全、小耳和小牙（LAMM 综合征，OMIM：610706）是一种罕见的 HL 综合征，其特征为先天性感觉神经性 HL、内耳发育不全、I 型小耳和小牙，由 FGF3 基因的双等位基因突变引起。使用全外显子组测序（WES），我们在三个无关联的维吾尔族家庭中发现了一种新的错义 FGF3 变体（c.137G>C，p.Arg46Pro（NM_005247.4）。根据 ACMG 指南，该变体被归类为意义不确定的变体，应用的标准为 PM3、PM2_Supporting、PP3 和 PP4。来自三个家庭的患者表现出不同的临床特征。我们在其中一个先证者中发现了一种新的表型，稀疏的毛发。我们的发现扩展了 LAMM 综合征的变体和表型谱，并为该疾病的诊断和发病机制研究提供了新的见解。
