一个家族性多发性淋巴管瘤病系由 FLT4/VEGFR3 基因突变 c.2774T > A 引起。
A family with Milroy disease caused by the FLT4/VEGFR3 gene variant c.2774 T > A.
机构信息
Key Laboratory of Reproductive Health and Medical Genetics, Liaoning Province Research Institute of Family Planning, China Medical University, 10 Puhe Street, Huanggu District, Shenyang, 110031, Liao Ning Province, China.
出版信息
BMC Med Genomics. 2021 Jun 8;14(1):151. doi: 10.1186/s12920-021-00997-w.
BACKGROUND
Milroy disease (MD) is a rare, autosomal-dominant disorder. Variants in the Fms-related tyrosine kinase 4 (FLT4/VEGFR3) gene cause the symptoms of this disease. In this report, we investigated the variant in a large Chinese family with MD.
METHODS
We conducted Sanger sequencing of exons 17-26 of FLT4/VEGFR3 (NM_182925.4). We assessed its pathogenicity based on the ACMG criteria and predicted it with an in silico program.
RESULTS
A heterozygous substitution (NM_182925.4 (FLT4/VEGFR3):c.2774 T>A, p. (Val925Glu)) was detected in all patients with MD but not in any healthy controls. The variant was evaluated as pathogenic according to the ACMG criteria and was predicted to be pathogenic using an in silico program.
CONCLUSIONS
In this report, we described a large family with MD caused by a missense variant in FLT4/VEGFR3 (NM_182925.4 (FLT4/VEGFR3_v001):c.2774 T>A, p. (Val925Glu)). There are phenotypic heterogeneities among family members, and further research should be conducted to explore the possible reasons.
背景
Milroy 病（MD）是一种罕见的常染色体显性遗传疾病。Fms 相关酪氨酸激酶 4（FLT4/VEGFR3）基因的变异导致了该病的症状。在本报告中，我们研究了一个大型 MD 中国家族中的该变异。
方法
我们对 FLT4/VEGFR3（NM_182925.4）的外显子 17-26 进行了 Sanger 测序。我们根据 ACMG 标准评估其致病性，并使用计算机程序进行预测。
结果
在所有 MD 患者中均检测到杂合替换（NM_182925.4（FLT4/VEGFR3）：c.2774T>A，p.（Val925Glu）），但在任何健康对照中均未检测到。根据 ACMG 标准，该变异被评估为致病性，并使用计算机程序预测为致病性。
结论
在本报告中，我们描述了一个由 FLT4/VEGFR3（NM_182925.4（FLT4/VEGFR3_v001）：c.2774T>A，p.（Val925Glu））中的错义变异引起的大型 MD 家族。家族成员之间存在表型异质性，应进一步研究以探讨可能的原因。
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