کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8310069 1538640 2016 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
A novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome
چکیده انگلیسی
Rett syndrome (RTT) is a severe X-linked dominant inheritance disorder with a wide spectrum of clinical manifestations. Mutations in Methyl CpG binding protein 2 (MECP2), Cyclin dependent kinase-like 5 (CDKL5) and Forkhead box G1 (FOXG1) have been associated with classic and/or variant RTT. This study was conducted to identify the responsible gene(s) in atypical RTT patient, and to examine the effect of the mutation on protein function. DNA sequence analysis showed a novel heterozygous mutation in CDKL5 identified as c.530A > G which resulted in an amino acid substitution at position 177, from tyrosine to cysteine. Genotyping analysis indicated that the mutation was not merely a single nucleotide polymorphism (SNP). We also revealed that patient's blood lymphocytes had random X-chromosome inactivation (XCI) pattern. Further examination by bioinformatics analysis demonstrated the mutation caused damage or deleterious in its protein. In addition, we demonstrated in vitro kinase assay of mutant protein showed impairment of its activity. Taken together, the results suggested the mutant CDKL5 was responsible for the disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinica Chimica Acta - Volume 459, 1 August 2016, Pages 132-136
نویسندگان
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