A splice-site variant (c.3289-1G>T) in OTOF underlies profound hearing loss in a Pakistani kindred.
A splice-site variant (c.3289-1G>T) in OTOF underlies profound hearing loss in a Pakistani kindred.
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OTOF 中的剪接位点变异 (c.3289–1G>T) 是巴基斯坦亲属严重听力损失的基础
DOI：
10.1186/s12920-020-00859-x
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发表时间：
2021-01-04
影响因子：
2.7
通讯作者：
Hu Z
中科院分区：
文献类型：
--
作者：
Ahmed A;Wang M;Khan R;Shah AA;Guo H;Malik S;Xia K;Hu Z
听力损失/耳聋是一种常见的耳科疾病，在巴基斯坦人口中发现，由于近亲结婚的高患病率，但全方位的遗传原因仍然是未知的。研究了一个有听力损失的大型巴基斯坦血缘亲属。进行全外显子组测序和桑格测序，以寻找潜在的疾病表型的候选基因。使用小基因测定和逆转录聚合酶链反应来评估剪接变体的影响。OTOF的剪接变体（NM_194248，c.3289-1G>T）与该巴基斯坦家族中的疾病表型共分离。单个碱基对的取代导致外显子27缺失10 bp（剪接变体1）或13 bp（剪接变体2），分别产生1141和1140个氨基酸的截短蛋白。我们的研究结果揭示了一个OTOF剪接位点变异的致病性在这个家庭的深度听力损失。
Hearing loss/deafness is a common otological disorder found in the Pakistani population due to the high prevalence of consanguineous unions, but the full range of genetic causes is still unknown. A large consanguineous Pakistani kindred with hearing loss was studied. Whole-exome sequencing and Sanger sequencing were performed to search for the candidate gene underlying the disease phenotype. A minigene assay and reverse transcription polymerase chain reaction was used to assess the effect of splicing variants. The splicing variants of OTOF (NM_194248, c.3289-1G>T) cosegregated with the disease phenotype in this Pakistani family. The substitution of a single base pair causes the deletion of 10 bp (splicing variant 1) or 13 bp (splicing variant 2) from exon 27, which results in truncated proteins of 1141 and 1140 amino acids, respectively. Our findings reveal an OTOF splice-site variant as pathogenic for profound hearing loss in this family.
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DOI：
10.1038/gim.2017.143
发表时间：
2018-04
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Almontashiri NAM;Alswaid A;Oza A;Al-Mazrou KA;Elrehim O;Tayoun AA;Rehm HL;Amr SS
通讯作者：
Amr SS
影响因子：
2.4
作者：
Vos B;Senterre C;Lagasse R;SurdiScreen Group;Levêque A
通讯作者：
Levêque A
影响因子：
3.9
作者：
Krawczak, Michael;Thomas, Nick S. T.;Cooper, David N.
通讯作者：
Cooper, David N.
影响因子：
4.8
作者：
Ramakrishnan, Neeliyath A.;Drescher, Marian J.;Drescher, Dennis G.
通讯作者：
Drescher, Dennis G.
影响因子：
64.5
作者：
Roux, Isabelle;Safieddine, Saaid;Petit, Christine
通讯作者：
Petit, Christine