Spectrum of variants in a large Chinese Gitelman syndrome cohort
Spectrum of variants in a large Chinese Gitelman syndrome cohort
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中国 Gitelman 综合征大型队列中的变异谱
DOI：
10.1111/cge.14422
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发表时间：
2023
影响因子：
3.5
通讯作者：
Ying Gu
中科院分区：
文献类型：
--
作者：
Lijun Mou;Mengyue Tang;Lina Zhu;Wanbing Lin;Ying Gu
Gitelman综合征（GS）是由SLC12A3双等位基因变异引起的。先前的一项研究表明，SLC12A3的大重排（LRGs）是基因检测灵敏度低的原因。然而，在中国GS患者中缺乏系统的LRGs筛查。采用大规模平行测序（MPS）和多重连接依赖探针扩增（MLPA）对临床诊断为GS的患者进行基因组DNA测序。在165例指标病例中，MPS鉴定出151例有两个或两个以上受影响的等位基因，14例有一个变异等位基因。27例中有20例经MLPA检出LRGs，其中15例经MPS检出疑似LRGs。在这20例LRGs中，MPS和MLPA结果相同的只有8例。单纯MLPA检出6例LRGs。6例中，MPS检测到E4_E6del， MLPA检测到E4_E5del和Intron6del。在102种不同的变体中，有30种是新颖的。LRGs 20例（12.1%）。12.1%的中国GS患者中发现了LRGs。我们发现MPS和MLPA是两种互补的技术，能够提高GS的诊断率。
Gitelman syndrome (GS) is caused by SLC12A3 biallelic variants. A previous study showed that large rearrangements (LRGs) of SLC12A3 accounted for the low sensitivity of genetic testing. However, a systematic screening for LRGs in Chinese GS patients is lacking. Massively parallel sequencing (MPS) and multiplex ligation‐dependent probe amplification (MLPA) were performed to sequence the genomic DNA of patients with clinically diagnosed GS. Of 165 index cases, MPS identified 151 cases with two or more affected alleles and 14 cases with one variant allele. LRGs were detected by MLPA in 20 out of 27 cases, including 15 cases with suspected LRGs by MPS. Among these 20 cases with LRGs, the results of MPS and MLPA were identical in only 8 cases. Additional LRGs in 6 cases were detected by MLPA alone. In 6 cases, E4_E6del was identified by MPS, while E4_E5del and Intron6del were identified by MLPA. Among the 102 distinct variants, 30 are novel. LRGs were found in 20 cases (12.1%). LRGs were found in 12.1% of our Chinese GS patients cohort. We show that MPS and MLPA are two complementary techniques with the ability to improve the diagnostic yield of GS.