Gumus Evren
a Department of Medical Genetics, Faculty of Medicine , University of Harran , Sanliurfa , Turkey.
Ophthalmic Genet. 2018 Jun;39(3):391-395. doi: 10.1080/13816810.2018.1432065. Epub 2018 Feb 8.
Warburg micro syndrome is a very rare autosomal recessive disorder characterized by a mutation in the RAB3GAP1, RAB3GAP2, RAB18, and TBC1D20 genes. Warburg Micro syndrome 2 and Martsolf syndrome are clinically overlapping conditions characterized by variable clinical signs counting postnatal growth retardation, cataract, intellectual deficiency, contractures, and central nervous system abnormalities due to RAB3GAP2 gene mutations. The RAB3GAP2 gene encodes a member of the Rab3 protein family, which is involved in regulated exocytosis of neurotransmitters and hormones.
We describe four siblings from healthy consanguineous Turkish parents with developmental delay, congenital cataract, and speech delay. In this study, we performed whole exom sequencing (WES) in a index patient. WES analyses in proposita showed a homozygous c.1998 + 1 G > A mutation in RAB3GAP2 gene. After the Sanger confirmation, the same mutation was detected in the other three siblings.
The four siblings had a novel splice site mutation in RAB3GAP2. This report compares the symptoms and features of the our patients with clinical summary of Warburg Micro syndrome 2 and Martsolf syndrome. Further reports will make possible knowing of the genetic and clinical backgrounds of this orphan diseases. Abbreviation: MRI: Magnetic resonance imaging.
瓦尔堡微综合征是一种非常罕见的常染色体隐性疾病，其特征是RAB3GAP1、RAB3GAP2、RAB18和TBC1D20基因发生突变。瓦尔堡微综合征2型和马茨洛夫综合征在临床上有重叠情况，其特征为多种临床症状，包括出生后生长发育迟缓、白内障、智力缺陷、挛缩以及由于RAB3GAP2基因突变导致的中枢神经系统异常。RAB3GAP2基因编码Rab3蛋白家族的一个成员，该家族参与神经递质和激素的调节性胞吐作用。
我们描述了来自健康近亲土耳其父母的四个兄弟姐妹，他们存在发育迟缓、先天性白内障和语言发育迟缓的情况。在本研究中，我们对一名索引患者进行了全外显子组测序（WES）。对先证者的WES分析显示RAB3GAP2基因存在纯合的c.1998+1 G>A突变。经桑格测序确认后，在其他三个兄弟姐妹中也检测到了相同的突变。
这四个兄弟姐妹在RAB3GAP2基因中存在一个新的剪接位点突变。本报告将我们患者的症状和特征与瓦尔堡微综合征2型和马茨洛夫综合征的临床总结进行了比较。进一步的报告将有助于了解这种罕见疾病的遗传和临床背景。缩写：MRI：磁共振成像。
