Mutation Analysis of Thin Basement Membrane Nephropathy.
Mutation Analysis of Thin Basement Membrane Nephropathy.
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DOI：
10.3390/genes13101779
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发表时间：
2022-10-02
期刊：
影响因子：
3.5
通讯作者：
Dohi, Kaoru
中科院分区：
文献类型：
--
作者：
Hirabayashi, Yosuke;Katayama, Kan;Mori, Mutsuki;Matsuo, Hiroshi;Fujimoto, Mika;Joh, Kensuke;Murata, Tomohiro;Ito, Masaaki;Dohi, Kaoru
关键词：
薄基底膜肾病（TBMN）的特征是在肾活检标本中观察到微血尿和薄肾小球基底膜。其主要原因是COL4A3或COL4A4的杂合突变，也会引起迟发性局灶节段性肾小球硬化症（FSGS）或常染色体显性阿尔波特综合征（ADAS）。使用桑格测序、多重连接依赖性探针扩增 (MLPA) 和外显子组测序对 13 例 TBMN 病例进行了分析。通过桑格测序，在 9 名患者的 COL4A3 或 COL4A4 中检测到 10 个杂合变异，其中 3 个是新变异。根据美国医学遗传学和基因组学学会指南，“可能致病”或“致病”的诊断率为 53.8%（13 名患者中有 7 名）。有八种单核苷酸变异，其中七种是胶原结构域中的甘氨酸取代，其中一种是剪接位点单核苷酸变异，另外两种是缺失变异。一名患者的 COL4A3 和 COL4A4 存在双基因变异。虽然 MLPA 分析显示阴性结果，但外显子组测序在 4 名患者的 FSGS 致病基因中发现了 3 个杂合变异，而桑格测序没有明显变异。由于具有 COL4A3 或 COL4A4 杂合突变的患者表现出从 TBMN 到 ADAS 的广泛疾病，因此有必要对这些患者进行仔细的随访。
Thin basement membrane nephropathy (TBMN) is characterized by the observation of microhematuria and a thin glomerular basement membrane on kidney biopsy specimens. Its main cause is heterozygous mutations of COL4A3 or COL4A4, which also cause late-onset focal segmental glomerulosclerosis (FSGS) or autosomal dominant Alport syndrome (ADAS). Thirteen TBMN cases were analyzed using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and exome sequencing. Ten heterozygous variants were detected in COL4A3 or COL4A4 in nine patients via Sanger sequencing, three of which were novel variants. The diagnostic rate of “likely pathogenic” or “pathogenic” under the American College of Medical Genetics and Genomics guidelines was 53.8% (7 out of 13 patients). There were eight single nucleotide variants, seven of which were glycine substitutions in the collagenous domain, one of which was a splice-site single nucleotide variant, and two of which were deletion variants. One patient had digenic variants in COL4A3 and COL4A4. While MLPA analyses showed negative results, exome sequencing identified three heterozygous variants in causative genes of FSGS in four patients with no apparent variants on Sanger sequencing. Since patients with heterozygous mutations of COL4A3 or COL4A4 showed a wide spectrum of disease from TBMN to ADAS, careful follow-up will be necessary for these patients.
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对Alport综合征的临床特征和遗传背景的回顾。
影响因子：
2.3
作者：
Nozu K;Nakanishi K;Abe Y;Udagawa T;Okada S;Okamoto T;Kaito H;Kanemoto K;Kobayashi A;Tanaka E;Tanaka K;Hama T;Fujimaru R;Miwa S;Yamamura T;Yamamura N;Horinouchi T;Minamikawa S;Nagata M;Iijima K
通讯作者：
Iijima K
DOI：
10.1038/s41431-021-00858-1
发表时间：
2021-08
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Savige J;Storey H;Watson E;Hertz JM;Deltas C;Renieri A;Mari F;Hilbert P;Plevova P;Byers P;Cerkauskaite A;Gregory M;Cerkauskiene R;Ljubanovic DG;Becherucci F;Errichiello C;Massella L;Aiello V;Lennon R;Hopkinson L;Koziell A;Lungu A;Rothe HM;Hoefele J;Zacchia M;Martic TN;Gupta A;van Eerde A;Gear S;Landini S;Palazzo V;Al-Rabadi L;Claes K;Corveleyn A;Van Hoof E;van Geel M;Williams M;Ashton E;Belge H;Ars E;Bierzynska A;Gangemi C;Lipska-Ziętkiewicz BS
通讯作者：
Lipska-Ziętkiewicz BS
影响因子：
15.9
作者：
Lemmink, HH;Nillesen, WN;Smeets, HJM
通讯作者：
Smeets, HJM
影响因子：
13.6
作者：
Badenas, C;Praga, M;Torra, R
通讯作者：
Torra, R
影响因子：
4
作者：
Mencarelli, Maria Antonietta;Heidet, Laurence;Renieri, Alessandra
通讯作者：
Renieri, Alessandra