Clinical manifestations and genetic analysis of a family with neurofibromatosis type 2

Abstract

Background

Neurofibromatosis type 2 (NF2) is an autosomal dominantly inherited disease with slow, yet potentially life-threatening progression.

Objective

We describe the clinical manifestations and genetic profile of a family with NF2.

Methods

We enrolled a 16-member family with NF2. We collected clinical examinations and imaging information. Genetic analysis was conducted through multiplex ligation-dependent probe amplification (MLPA). The SALSA MLPA probemix P044-B2 NF2 kit was used to detect genetic variations in genomic upstream and 17 exons of the NF2 gene.

Results

The most common clinical manifestation was hearing impairment (37.5%), followed by tinnitus (18.8%). Four participants had vestibular schwannoma: 2 were bilateral and 2 unilateral, and tumor size ranged from 86.3 to 5064 mm³. A weak correlation between hearing impairment and tumor size was observed. Genetic analysis revealed that the DNA dosages of exons 9, 10, and 11 of the NF2 gene in 3 diseased family members (participants #3, #5, and #11) were higher than those in the controls. However, we could not detect an indicative abnormal DNA dosage of NF2 in participant #6 despite such a dosage being considered a diagnostic indicator of NF2.

Conclusions

Hearing impairment was the most common clinical manifestation in this family. The NF2 gene is a gene of interest that warrants familial genetic screening.

Chinese Abstract

背景：II型神经纤维瘤病 (NF2) 是一种常染色体显性遗传疾病, 具有缓慢、但可能危及生命的病程。

目的：我们描述了一个 NF2 家庭的临床表现和遗传特征。

方法：我们招募了一个 16 人的 NF2 家庭, 收集了临床检查和影像信息。通过多重连接依赖性探针扩增进行遗传分析(MLPA)。 SALSA MLPA 探针组合P044-B2 NF2 试剂盒用于检测基因上游中的遗传变异和NF2基因组的17 个外显子。

结果：最常见的临床表现是听力障碍（37.5%）, 其次是耳鸣（18.8%）。四名参与者患有前庭神经鞘瘤：2 名双侧和 2 名单侧, 肿瘤大小从 86.3 到 5064 mm³。 观察到听力障碍与肿瘤大小之间的弱相关性。遗传分析表明, 3个患病家庭成员（参与者#3、#5和#11）的NF2 基因的外显子 9、10 和 11 的 DNA 剂量高于对照组。然而, 我们无法检测到参与者Q2 #6的NF2 指示性异常 DNA 剂量。

结论：听力障碍是该家族最常见的临床表现。 NF2基因引起我们的注意, 值得进行家族遗传筛查。

Keywords:

• Neurofibromatosis type 2
• clinical manifestations
• NF2 gene

Disclosure statement

No potential conflict of interest was reported by the author(s). The article has not been published previously and is not being considered for publication in other journals.