A splice-site variant (c.3289-1G>T) in OTOF underlies profound hearing loss in a Pakistani kindred

被引：5

作者：

Ahmed, Ashfaque ^{[1
,2
]}

Wang, Meng ^{[1
,2
]}

Khan, Rizwan ^{[1
,2
]}

Shah, Abid Ali ^{[1
,2
]}

Guo, Hui ^{[1
,2
]}

Malik, Sajid ^{[3
]}

Xia, Kun ^{[1
,2
]}

Hu, Zhengmao ^{[1
,2
,4
]}

机构：

[1] Cent South Univ, Sch Life Sci, Ctr Med Genet, Changsha 410078, Hunan, Peoples R China

[2] Cent South Univ, Sch Life Sci, Hunan Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China

[3] Quaid I Azam Univ, Fac Biol Sci, Dept Zool, Human Genet Program, Islamabad, Pakistan

[4] Cent South Univ, Sch Life Sci, Hunan Key Lab Anim Models Human Dis, Changsha 410078, Hunan, Peoples R China

来源：

BMC MEDICAL GENOMICS | 2021年 / 14卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Hearing loss; OTOF; Splice acceptor site; Minigene; CONSENSUS RECOMMENDATION; MEDICAL GENETICS; AMERICAN-COLLEGE; OTOFERLIN; DEAFNESS; DFNB9; EXOCYTOSIS; MUTATIONS; GENOMICS; PROTEIN;

D O I：

10.1186/s12920-020-00859-x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background 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. Methods 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. Results 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. Conclusion Our findings reveal an OTOF splice-site variant as pathogenic for profound hearing loss in this family.

引用

页数：8

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