Screening of MECP2 coding sequence in patients with phenotypes of decreasing likelihood for Rett syndrome: a cohort of 171 cases

Kammoun, Fatma

doi:10.1136/jmg.2003.014480

Cited by 40 publications

(39 citation statements)

References 49 publications

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“…The four patients who had deletions in exon 4 did not experience the characteristic seizures and scoliosis whereas the six patients with deletions in exons 3 and 4 endured seizures, complete loss of hand function, no language ability, and accompanying scoliosis (Pan et al 2006, submitted). One previous study suggested that RTT phenotype is more likely to be complete as the child grows up (Kammoun et al 2004). In our study, the majority of patients were younger than 10 years.…”

Section: Cdkl5 Mutation Detection By Dhplc Analysismentioning

confidence: 99%

“…Recent reports described a range of 65-79% for the mutation detection rate among patients with atypical RTT (Smeets et al , 2005. Kanmmoun et al recommended selecting well-defined clinical criteria while searching for MECP2 mutations, as all individual variables did not exhibit similar weights (Kammoun et al 2004). Thus, we hypothesized that the different The total mutation frequency among all RTT patients was 84.3% (102/121).…”

Section: Cdkl5 Mutation Detection By Dhplc Analysismentioning

confidence: 99%

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MECP2 and CDKL5 gene mutation analysis in Chinese patients with Rett syndrome

Pan

Bao

et al. 2006

J Hum Genet

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Rett syndrome (RTT) is a progressive neurodevelopmental disorder that is caused by mutations in the X-linked methyl-CpG-binding protein2 (MECP2) gene. In this study, the MECP2 sequences in 121 unrelated Chinese patients with classical or atypical RTT were screened for deletions and mutations. In all, we identified 45 different MECP2 mutations in 102 of these RTT patients. The p. T158M mutation (15.7%) was the most common, followed in order of frequency by p. R168X (11.8%), p. R133C (6.9%), p. R270X (6.9%), p. G269fs (6.9%), p. R255X (4.9%), and p. R306C (3.9%). In addition, we identified five novel MECP2 mutations: three missense (p. K305E, p. V122M, p. A358T), one insertion (c.45-46ins-GGAGGA), and one 22 bp deletion (c.881-902del22). Large deletions represented 10.5% of all identified MECP2 mutations. Conversely, mutations in exon 1 appeared to be rare (0.9%). The remaining cases without MECP2 mutations were screened for the cyclin-dependent kinase-like 5 (CDKL5) gene using denaturing high-performance liquid chromatography (DHPLC). One synonymous mutation (p. I72I) was found in exon 5, suggesting that CDKL5 is a rare cause of RTT. The overall MECP2 mutation detection rate for this patient series was 84.3:87.9% in 107 classical RTT cases and 57.1% in 14 atypical RTT cases. Moreover, there were two patients with homozygous mutations and normal female karyotypes. However, we did not pinpoint a significant relationship between genotype and phenotype in these cases.

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Section: Cdkl5 Mutation Detection By Dhplc Analysismentioning

confidence: 99%

Section: Cdkl5 Mutation Detection By Dhplc Analysismentioning

confidence: 99%

MECP2 and CDKL5 gene mutation analysis in Chinese patients with Rett syndrome

Pan

Bao

et al. 2006

J Hum Genet

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“…In smaller groups this is situated in a broad interval between 35 and 77% of cases (27). In our study, we report the identification of mutations in the coding sequence of MECP2 in 44% of the investigated cases.…”

Section: Resultsmentioning

confidence: 63%

“…The selection of patients according to strict clinical criteria are reported to lead to a high likelihood of finding a mutation in the MECP2 coding region, nearly to 90% when applied to large series (27). In smaller groups this is situated in a broad interval between 35 and 77% of cases (27).…”

Section: Resultsmentioning

confidence: 99%

Mutation analysis of the MECP2 gene in Romanian females with Rett syndrome

Dumitriu¹,

Klootwijk²,

Issler³

et al. 2013

Romanian Review of Laboratory Medicine

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“…[5][6][7] Mutations in the methyl-CpG-binding protein, MECP2 gene, were identified as disease causing, 8 and according to data published, MECP2 mutations account for B80-96% of the classical Rett cases 9,10 and 40-50% of atypical Rett manifestations. 11 The MECP2 gene is located at Xq28 and therefore it is subject to X-chromosome inactivation. 12 It comprises four exons and encodes two alternatively spliced isoforms: the 498 amino-acid MeCP2E1 encompassing exons 1, 3 and 4, and MeCP2E2 of 486 residues comprising exons 2, 3 and 4.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations

et al. 2010

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Rett syndrome (RTT) is characterized by a relatively specific clinical phenotype. We screened 152 individuals with RTT phenotype. A total of 22 different known MECP2 mutations were identified in 42 subjects (27.6%). Of the 22 mutations, we identified 7 (31.8%) frameshift-causing deletions, 4 (18.2%) nonsense, 10 (45.5%) missense mutations and one insertion (4.5%). The most frequent pathologic changes were: p.Thr158Met (14.2%) and p.Arg133Cys (11.9%) missense, and p.Arg255Stop (9.5%) and p.Arg294Stop (9.5%) nonsense mutations. We also detected the c.925C4T (p.Arg309Trp) mutation in an affected patient, whose role in RTT pathogenesis is still unknown. Patients without detectable MECP2 defects were screened for mutations of cyclin-dependent kinase-like 5 (CDKL5) gene, responsible for the early-onset variant of RTT. We discovered two novel mutations: c.607G4T resulting in a termination codon at aa203, disrupting the catalytic domain, and c.1708G4T leading to a stop at aa570 of the C terminus. Both patients with CDKL5 mutation presented therapy-resistant epilepsy and a phenotype fitting with the diagnosis of early-onset variant of RTT. No FOXG1 mutation was detected in any of the remaining patients. A total of 110 (72.5%) patients remained without molecular genetic diagnosis that necessitates further search for novel gene mutations in this phenotype. Our results also suggest the need of screening for CDKL5 mutations in patients with Rett phenotype tested negative for MECP2 mutations.

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Screening of MECP2 coding sequence in patients with phenotypes of decreasing likelihood for Rett syndrome: a cohort of 171 cases

Cited by 40 publications

References 49 publications

MECP2 and CDKL5 gene mutation analysis in Chinese patients with Rett syndrome

MECP2 and CDKL5 gene mutation analysis in Chinese patients with Rett syndrome

Mutation analysis of the MECP2 gene in Romanian females with Rett syndrome

Analysis of Hungarian patients with Rett syndrome phenotype for MECP2, CDKL5 and FOXG1 gene mutations

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