BACKGROUND Rett syndrome is a monogenic X-linked dominant condition that affects 1/(10000-15000)girls due to de novo mutations in the methyl-CpG binding protein 2(MECP2)gene mapped to chromosome Xq28.The disease-causi...BACKGROUND Rett syndrome is a monogenic X-linked dominant condition that affects 1/(10000-15000)girls due to de novo mutations in the methyl-CpG binding protein 2(MECP2)gene mapped to chromosome Xq28.The disease-causing gene was identified as a mutation in the MECP2 gene,which is found in approximately 80%of patients diagnosed with Rett syndrome.Although chromosomal changes resulting in del(15)(q11q13)are usually associated with Angelman and Prader-Willi syndrome,very few cases,if any,of Rett syndrome with terminal 15q22-qter deletion have been published in English literature.CASE SUMMARY In this study,we report an unusual and rare clinical presentation of Rett syndrome in a 12-year-old Sudanese girl.The patient was brought in by her parents,complaining of gradual onset of abnormal walking,abnormal hand movement,loss of speech,and mental retardation for ten years.There was no reported history of convulsions or loss of consciousness.Clinical examination revealed microcephaly with no other apparent dysmorphic features,intact cranial nerves,and abnormal gait.She showed repetitive and stereotyped behaviors,including hand flapping,stimming,and chest pounding,which were concomitant with autism spectrum disorder.Magnetic resonance imaging and electroencephalography investigations were normal,and cytogenetic analysis showed 46,XX,del(15)(q22qter).Further molecular analysis using whole sequencing of MECP2 revealed an alteration cytosine>thymine at nucleotide 401,leading to phenylalanine replacing a serine at amino acid position 134.CONCLUSION This case,the first reported instance of Rett syndrome in Sudan,is of significant interest.The patient carries both the MECP2 gene mutation and the chromosome 15q22-qter deletion,which may explain the autistic behavior with atypical presentation of Rett syndrome.This report expands the genetic diversity of Rett syndrome,demonstrating how co-occurring 15q22-qter deletions can reshape MECP2-associated phenotypes in Rett syndrome.展开更多
Rett syndrome(RTT),an X-linked dominant neurodevelopmental disorder characterized by regression of language,stereotype hand movement and loss of purposeful hand use,is primarily caused by mutation of menthyl-CpG-bindi...Rett syndrome(RTT),an X-linked dominant neurodevelopmental disorder characterized by regression of language,stereotype hand movement and loss of purposeful hand use,is primarily caused by mutation of menthyl-CpG-binding protein 2(MECP2).The 76 kb human MECP2 is characterized by three salient features: a very large intron 2(60 kb),an 8.5 kb 3′-UTR with highly conserved regions and different polyadenylation sites,and a 40 kb intergenic region separating MECP2 from the nearest upstream gene.There are two isoforms of MeCP2,MeCP2e1 and MeCP2e2.The differences between the two isoforms,the function of the 3′-UTR and the long-range cis-regulatory sequences in the intergenic region were extensively studied.In contrast to initial report,recent studies show that MeCP2 binds not only to methylated promoters and silence transcription,but also to the sites outside of genes containing only a few of CpG islands.Furthermore,MeCP2 can function as both an activator and a repressor of transcription.Abstract:SUMM ARY Rett syndrome(RTT),an X-linked dom inant neurodevelopmental d isorder characterized by regression of language,stereotype hand movement and loss of purposeful hand use,is primarily caused by mutation of menthyl-CpG-bind ing protein 2(MECP2).The 76 kb humanMECP2is characterized by three salient features: a very large intron 2(60 kb),an 8.5 kb 3′-UTR with highly conserved regions and d ifferent polyadenylation sites,and a 40 kb intergenic region separatingMECP2from the nearest up-stream gene.There are two isoforms ofMeCP2,MeCP2e1 and MeCP2e2.The d ifferences between the two isoforms,the function of the 3′-UTR and the long-range cis-regulatory sequences in the intergenic re-gion were extensively stud ied.In contrast to initial report,recent stud ies show thatMeCP2 binds not only to methylated promoters and silence transcription,but also to the sites outside of genes containing only a few of CpG islands.Furthermore,MeCP2 can function as both an activator and a repressor of transcrip-tion.展开更多
Rett综合征（Rett syndrome,RTT）是一种严重影响儿童精神运动发育的疾病,是女性严重智力低下的重要原因之一,男童罕见,女童患病率为7/10万～10/10万。1999年Amir等确定位于Xq28的甲基化CpG结合蛋白2基因（methyl—CpG-binding protein ...Rett综合征（Rett syndrome,RTT）是一种严重影响儿童精神运动发育的疾病,是女性严重智力低下的重要原因之一,男童罕见,女童患病率为7/10万～10/10万。1999年Amir等确定位于Xq28的甲基化CpG结合蛋白2基因（methyl—CpG-binding protein 2,MECP2）是RTT的致病基因。展开更多
文摘BACKGROUND Rett syndrome is a monogenic X-linked dominant condition that affects 1/(10000-15000)girls due to de novo mutations in the methyl-CpG binding protein 2(MECP2)gene mapped to chromosome Xq28.The disease-causing gene was identified as a mutation in the MECP2 gene,which is found in approximately 80%of patients diagnosed with Rett syndrome.Although chromosomal changes resulting in del(15)(q11q13)are usually associated with Angelman and Prader-Willi syndrome,very few cases,if any,of Rett syndrome with terminal 15q22-qter deletion have been published in English literature.CASE SUMMARY In this study,we report an unusual and rare clinical presentation of Rett syndrome in a 12-year-old Sudanese girl.The patient was brought in by her parents,complaining of gradual onset of abnormal walking,abnormal hand movement,loss of speech,and mental retardation for ten years.There was no reported history of convulsions or loss of consciousness.Clinical examination revealed microcephaly with no other apparent dysmorphic features,intact cranial nerves,and abnormal gait.She showed repetitive and stereotyped behaviors,including hand flapping,stimming,and chest pounding,which were concomitant with autism spectrum disorder.Magnetic resonance imaging and electroencephalography investigations were normal,and cytogenetic analysis showed 46,XX,del(15)(q22qter).Further molecular analysis using whole sequencing of MECP2 revealed an alteration cytosine>thymine at nucleotide 401,leading to phenylalanine replacing a serine at amino acid position 134.CONCLUSION This case,the first reported instance of Rett syndrome in Sudan,is of significant interest.The patient carries both the MECP2 gene mutation and the chromosome 15q22-qter deletion,which may explain the autistic behavior with atypical presentation of Rett syndrome.This report expands the genetic diversity of Rett syndrome,demonstrating how co-occurring 15q22-qter deletions can reshape MECP2-associated phenotypes in Rett syndrome.
文摘Rett syndrome(RTT),an X-linked dominant neurodevelopmental disorder characterized by regression of language,stereotype hand movement and loss of purposeful hand use,is primarily caused by mutation of menthyl-CpG-binding protein 2(MECP2).The 76 kb human MECP2 is characterized by three salient features: a very large intron 2(60 kb),an 8.5 kb 3′-UTR with highly conserved regions and different polyadenylation sites,and a 40 kb intergenic region separating MECP2 from the nearest upstream gene.There are two isoforms of MeCP2,MeCP2e1 and MeCP2e2.The differences between the two isoforms,the function of the 3′-UTR and the long-range cis-regulatory sequences in the intergenic region were extensively studied.In contrast to initial report,recent studies show that MeCP2 binds not only to methylated promoters and silence transcription,but also to the sites outside of genes containing only a few of CpG islands.Furthermore,MeCP2 can function as both an activator and a repressor of transcription.Abstract:SUMM ARY Rett syndrome(RTT),an X-linked dom inant neurodevelopmental d isorder characterized by regression of language,stereotype hand movement and loss of purposeful hand use,is primarily caused by mutation of menthyl-CpG-bind ing protein 2(MECP2).The 76 kb humanMECP2is characterized by three salient features: a very large intron 2(60 kb),an 8.5 kb 3′-UTR with highly conserved regions and d ifferent polyadenylation sites,and a 40 kb intergenic region separatingMECP2from the nearest up-stream gene.There are two isoforms ofMeCP2,MeCP2e1 and MeCP2e2.The d ifferences between the two isoforms,the function of the 3′-UTR and the long-range cis-regulatory sequences in the intergenic re-gion were extensively stud ied.In contrast to initial report,recent stud ies show thatMeCP2 binds not only to methylated promoters and silence transcription,but also to the sites outside of genes containing only a few of CpG islands.Furthermore,MeCP2 can function as both an activator and a repressor of transcrip-tion.
文摘Rett综合征（Rett syndrome,RTT）是一种严重影响儿童精神运动发育的疾病,是女性严重智力低下的重要原因之一,男童罕见,女童患病率为7/10万～10/10万。1999年Amir等确定位于Xq28的甲基化CpG结合蛋白2基因（methyl—CpG-binding protein 2,MECP2）是RTT的致病基因。
