Kelch-like family member 17(KLHL17)is predominantly expressed in the brain and plays a crucial role in neuronal development and function,deletions and/or mutations in KLHL17 have been linked to neurodevelopmental diso...Kelch-like family member 17(KLHL17)is predominantly expressed in the brain and plays a crucial role in neuronal development and function,deletions and/or mutations in KLHL17 have been linked to neurodevelopmental disorders in humans,e.g.,intellectual disability,autism spectrum disorder,and infantile spasms,but the etiology and pathogenesis remain largely enigmatic.1,2 As a member of the family of the Kelch proteins,KLHL17 contains an N-terminal BTB/POZ domain followed by a BACK domain and four to six tandem Kelch motifs at the C-terminal region(Fig.S1A).1,3 Previously,we identified a novel de novo variant in KLHL17(c.701C>T;p.P234L)in a cohort of 225 Chinese children with developmental delay/intellectual disability based on whole-exome sequencing(1/225),the mutation located in the BACK domain,a very high conversed region(Fig.S1B),and the affected boy presented with developmental delay,intellectual disability,hypotonia,and abnormal brainstem auditory evoked potential signal.4 The finding may offer a new clue to investigate the molecular pathogenesis of KLHL17 gene in neurodevelopmental disorders.展开更多
基金funded by the National Natural Science Foundation of China(No.82160620)the Natural Science Foundation of Guangxi Province,China(No.2023GXNSFAA026036)the Guangxi College Students Innovation and Entrepreneurship Training Program(China)(No.S202310601164).
文摘Kelch-like family member 17(KLHL17)is predominantly expressed in the brain and plays a crucial role in neuronal development and function,deletions and/or mutations in KLHL17 have been linked to neurodevelopmental disorders in humans,e.g.,intellectual disability,autism spectrum disorder,and infantile spasms,but the etiology and pathogenesis remain largely enigmatic.1,2 As a member of the family of the Kelch proteins,KLHL17 contains an N-terminal BTB/POZ domain followed by a BACK domain and four to six tandem Kelch motifs at the C-terminal region(Fig.S1A).1,3 Previously,we identified a novel de novo variant in KLHL17(c.701C>T;p.P234L)in a cohort of 225 Chinese children with developmental delay/intellectual disability based on whole-exome sequencing(1/225),the mutation located in the BACK domain,a very high conversed region(Fig.S1B),and the affected boy presented with developmental delay,intellectual disability,hypotonia,and abnormal brainstem auditory evoked potential signal.4 The finding may offer a new clue to investigate the molecular pathogenesis of KLHL17 gene in neurodevelopmental disorders.
