Q型蛋白酪氨酸磷酸酶受体(Receptor type protein tyrosine phosphatase Q,PTPRQ)是Ⅲ型酪氨酸磷酸酶受体家族的成员,具有磷酸酪氨酸磷酸酶和磷脂酰肌醇磷酸酶活性,可调节细胞的增殖、凋亡、分化等多种细胞内生理过程。在内耳方面,PTPR...Q型蛋白酪氨酸磷酸酶受体(Receptor type protein tyrosine phosphatase Q,PTPRQ)是Ⅲ型酪氨酸磷酸酶受体家族的成员,具有磷酸酪氨酸磷酸酶和磷脂酰肌醇磷酸酶活性,可调节细胞的增殖、凋亡、分化等多种细胞内生理过程。在内耳方面,PTPRQ被认为是一种耳聋基因,主要参与耳蜗和前庭毛细胞的发育及成熟。研究发现,PTPRQ基因突变可导致两种非综合征性遗传性耳聋,包括DFNB84A型常染色体隐性耳聋和DFNA73型常染色体显性耳聋,两种耳聋的临床表型差异很大,这提示了其致病机制的不同。既往研究报道了多个耳聋家系与PTPRQ基因突变相关,本文对此做一综述,有助于识别治疗耳聋相关疾病的新靶点,并为PTPRQ突变致病机理的进一步研究提供理论参考。展开更多
ObjectivesThe PTPRQ gene is essential for preserving the structure and function of stereocilia in inner ear.However,research on splicing mutations within this gene is limited.This study aims to investigate novel splic...ObjectivesThe PTPRQ gene is essential for preserving the structure and function of stereocilia in inner ear.However,research on splicing mutations within this gene is limited.This study aims to investigate novel splicing mutations in PTPRQ,clarify their molecular mechanisms,and provide new insights into the genetic factors associated with hearing loss,ultimately enhancing diagnostic accuracy.MethodClinical data and peripheral blood samples were obtained from members of a family with congenital hearing loss.Variants were identified through high-throughput sequencing and confirmed by Sanger sequencing to ensure genealogical co-segregation.The splicing effects of PTPRQ variants were evaluated using bioinformatics tools and minigene assays.ResultsWe used whole exome sequencing to identify novel double compound heterozygous splice-altering variants(c.5426+1 G>A and c.6603-3 T>G)in the PTPRQ gene with DFNB84A.We molecularly characterized these variants,and they were found to co-segregate with the disease within the family.Minigene assays and Sanger sequencing confirmed that the c.6603-3 T>G variant caused exon 43 skipping,resulting in a frameshift mutation(p.Ser2201ArgfsTer112).Further bioinformatic analysis supported these findings.ConclusionsThis study identifies a novel compound heterozygous splicing variant in the PTPRQ gene in a Chinese family with DFNB84A,expanding the known spectrum of PTPRQ mutations.These findings enhance the understanding of PTPRQ-related hearing loss and may aid in early diagnosis,prevention,and therapeutic strategies.展开更多
受体型蛋白酪氨酸磷酸酶Q(Receptor type protein tyrosine phosphatase Q,PTPRQ)作为一种蛋白酪氨酸磷酸酶,能催化不同的底物,参与多种细胞内的功能。PTPRQ基因突变可导致常染色体隐性和显性非综合征性耳聋DFNB84A型和DFNA73型耳聋的发...受体型蛋白酪氨酸磷酸酶Q(Receptor type protein tyrosine phosphatase Q,PTPRQ)作为一种蛋白酪氨酸磷酸酶,能催化不同的底物,参与多种细胞内的功能。PTPRQ基因突变可导致常染色体隐性和显性非综合征性耳聋DFNB84A型和DFNA73型耳聋的发生,两型耳聋的临床表型差异提示了其致病机制的不同。在内耳,PTPRQ主要位于前庭及耳蜗毛细胞纤毛基底部,参与耳蜗毛细胞纤毛束的成熟,对维持纤毛的形态和功能具有重要作用。目前世界上报道的与PTPRQ突变相关的耳聋家系有14个,多数隐性突变是因截短或缺失而影响了PTPRQ的酶结构域的功能,但是PTPRQ的显性突变致病机理仍不清楚。有关该基因显、隐性突变致病机制的更深入研究可为相关病例的针对性干预提供理论依据。展开更多
文摘Q型蛋白酪氨酸磷酸酶受体(Receptor type protein tyrosine phosphatase Q,PTPRQ)是Ⅲ型酪氨酸磷酸酶受体家族的成员,具有磷酸酪氨酸磷酸酶和磷脂酰肌醇磷酸酶活性,可调节细胞的增殖、凋亡、分化等多种细胞内生理过程。在内耳方面,PTPRQ被认为是一种耳聋基因,主要参与耳蜗和前庭毛细胞的发育及成熟。研究发现,PTPRQ基因突变可导致两种非综合征性遗传性耳聋,包括DFNB84A型常染色体隐性耳聋和DFNA73型常染色体显性耳聋,两种耳聋的临床表型差异很大,这提示了其致病机制的不同。既往研究报道了多个耳聋家系与PTPRQ基因突变相关,本文对此做一综述,有助于识别治疗耳聋相关疾病的新靶点,并为PTPRQ突变致病机理的进一步研究提供理论参考。
基金supported in part by the Natural Science Foundation of Shandong Province(no.ZR2022QH373,ZR2022QH292 and ZR2023MH2474).
文摘ObjectivesThe PTPRQ gene is essential for preserving the structure and function of stereocilia in inner ear.However,research on splicing mutations within this gene is limited.This study aims to investigate novel splicing mutations in PTPRQ,clarify their molecular mechanisms,and provide new insights into the genetic factors associated with hearing loss,ultimately enhancing diagnostic accuracy.MethodClinical data and peripheral blood samples were obtained from members of a family with congenital hearing loss.Variants were identified through high-throughput sequencing and confirmed by Sanger sequencing to ensure genealogical co-segregation.The splicing effects of PTPRQ variants were evaluated using bioinformatics tools and minigene assays.ResultsWe used whole exome sequencing to identify novel double compound heterozygous splice-altering variants(c.5426+1 G>A and c.6603-3 T>G)in the PTPRQ gene with DFNB84A.We molecularly characterized these variants,and they were found to co-segregate with the disease within the family.Minigene assays and Sanger sequencing confirmed that the c.6603-3 T>G variant caused exon 43 skipping,resulting in a frameshift mutation(p.Ser2201ArgfsTer112).Further bioinformatic analysis supported these findings.ConclusionsThis study identifies a novel compound heterozygous splicing variant in the PTPRQ gene in a Chinese family with DFNB84A,expanding the known spectrum of PTPRQ mutations.These findings enhance the understanding of PTPRQ-related hearing loss and may aid in early diagnosis,prevention,and therapeutic strategies.
文摘受体型蛋白酪氨酸磷酸酶Q(Receptor type protein tyrosine phosphatase Q,PTPRQ)作为一种蛋白酪氨酸磷酸酶,能催化不同的底物,参与多种细胞内的功能。PTPRQ基因突变可导致常染色体隐性和显性非综合征性耳聋DFNB84A型和DFNA73型耳聋的发生,两型耳聋的临床表型差异提示了其致病机制的不同。在内耳,PTPRQ主要位于前庭及耳蜗毛细胞纤毛基底部,参与耳蜗毛细胞纤毛束的成熟,对维持纤毛的形态和功能具有重要作用。目前世界上报道的与PTPRQ突变相关的耳聋家系有14个,多数隐性突变是因截短或缺失而影响了PTPRQ的酶结构域的功能,但是PTPRQ的显性突变致病机理仍不清楚。有关该基因显、隐性突变致病机制的更深入研究可为相关病例的针对性干预提供理论依据。
