Background Sandhoff disease(SD)i s an autosomal recessive lysosomal disease with clinical manifestations such as epilepsy,psychomotor retardation and developmental delay.However,infantile SD with onset of infantile ep...Background Sandhoff disease(SD)i s an autosomal recessive lysosomal disease with clinical manifestations such as epilepsy,psychomotor retardation and developmental delay.However,infantile SD with onset of infantile epilepsy spasm syndrome(IESS)is extremely rare.Case presentation The case presented here was a 22-month-old boy,who presented with IESS and psychomotor retardation/regression at 6 months of age.The patient showed progressive aggravation of seizures and excessive startle responses.The whole exome sequencing data,which initially revealed negative results,were reanalyzed and indicated a homozygous mutation at the c.1613+4del splice site of the HEXB gene.The activities ofβ-hexosaminidase A and total hexosaminidase were significantly decreased.The fundus examination showed cherry red spots at the macula.Conclusions IESS can be an epileptic phenotype of infantile SD.Clinical phenotypes should be adequately collected in genetic testing.In the case of negative sequencing results,gene variant reanalysis can be performed when the patients show clinically suspicious indications.展开更多
Deciphering the relationship between human proteins(genes)and phenotypes is one of the fundamental tasks in phenomics research.The Human Phenotype Ontology(HPO)builds upon a standardized logical vocabulary to describe...Deciphering the relationship between human proteins(genes)and phenotypes is one of the fundamental tasks in phenomics research.The Human Phenotype Ontology(HPO)builds upon a standardized logical vocabulary to describe the abnormal phenotypes encountered in human diseases and paves the way towards the computational analysis of their genetic causes.To date,many computational methods have been proposed to predict the HPO annotations of proteins.In this paper,we conduct a comprehensive review of the existing approaches to predicting HPO annotations of novel proteins,identifying missing HPO annotations,and prioritizing candidate proteins with respect to a certain HPO term.For each topic,we first give the formalized description of the problem,and then systematically revisit the published literatures highlighting their advantages and disadvantages,followed by the discussion on the challenges and promising future directions.In addition,we point out several potential topics to be worthy of exploration including the selection of negative HPO annotations and detecting HPO misannotations.We believe that this review will provide insight to the researchers in the field of computational phenotype analyses in terms of comprehending and developing novel prediction algorithms.展开更多
基金funded by the Capital’s Funds for Health Improvement and Research(No.2022-1-5081).
文摘Background Sandhoff disease(SD)i s an autosomal recessive lysosomal disease with clinical manifestations such as epilepsy,psychomotor retardation and developmental delay.However,infantile SD with onset of infantile epilepsy spasm syndrome(IESS)is extremely rare.Case presentation The case presented here was a 22-month-old boy,who presented with IESS and psychomotor retardation/regression at 6 months of age.The patient showed progressive aggravation of seizures and excessive startle responses.The whole exome sequencing data,which initially revealed negative results,were reanalyzed and indicated a homozygous mutation at the c.1613+4del splice site of the HEXB gene.The activities ofβ-hexosaminidase A and total hexosaminidase were significantly decreased.The fundus examination showed cherry red spots at the macula.Conclusions IESS can be an epileptic phenotype of infantile SD.Clinical phenotypes should be adequately collected in genetic testing.In the case of negative sequencing results,gene variant reanalysis can be performed when the patients show clinically suspicious indications.
文摘Deciphering the relationship between human proteins(genes)and phenotypes is one of the fundamental tasks in phenomics research.The Human Phenotype Ontology(HPO)builds upon a standardized logical vocabulary to describe the abnormal phenotypes encountered in human diseases and paves the way towards the computational analysis of their genetic causes.To date,many computational methods have been proposed to predict the HPO annotations of proteins.In this paper,we conduct a comprehensive review of the existing approaches to predicting HPO annotations of novel proteins,identifying missing HPO annotations,and prioritizing candidate proteins with respect to a certain HPO term.For each topic,we first give the formalized description of the problem,and then systematically revisit the published literatures highlighting their advantages and disadvantages,followed by the discussion on the challenges and promising future directions.In addition,we point out several potential topics to be worthy of exploration including the selection of negative HPO annotations and detecting HPO misannotations.We believe that this review will provide insight to the researchers in the field of computational phenotype analyses in terms of comprehending and developing novel prediction algorithms.
