1995 Fiscal Year Final Research Report Summary
Molecular Studies of FMR-1 mutations in Chidlhood Developmental Disorders
| Project/Area Number |
06670796
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Okayama University |
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Principal Investigator |
KANAZAKI Susumu Okayama. Univ.Hospital Pediatrics, Lecturer, 医学部・附属病院, 講師 (90224873)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJI Kazushiro Okayama Univ.Hospital, Pediatrics, Resident, 医学部・附属病院, 医員
YOKOYAMA Yuji Okayama Univ.Hospital, Pediatrics, Instructor, 医学部・付属病院, 助手 (00240226)
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| Project Period (FY) |
1994 – 1995
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| Keywords | developmental disorder / fragile X syndrome / FMR-1 / triplet repeat expansion / gene expression / PCR |
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| Research Abstract |
The FMR-1 gene isolated from patients with fragile X syndrome appears to play an important role in recognition. Virtually all of patients with fragile X syndrome have expansions of CGG repeats in 5'-UTR of FMR-1 and methylation of the upstream CpG island, but different mutations of the FMR-1 gene are known to be associated with different phenotypes. We conducted molecular studies of FMR-1 mutations in childrens with developmental disorders, to study whether a FMR-1 mutation could be a cause for other developmental disorder than fragile X syndrome. The subjects consisted of 60 children with mental retardation, 59 with behavior disorders, 15 with autistic disorders, and 16 with learning disorders. Southern blot analysis showed expansion of the CGG repeat in two of 60 mental retardates and one of 15 autistic children but none in patients with abnormal behaviors or learning disorders. The evaluation of the 8th exon by RT-PCR of RNAs from 7 carriers of CGG repeat expansions in a family with fragile X syndrome showed normal expression in premutaion carriers but no expression in both male and female carriers with full mutations of CGG repeat expansion. An experiment of SSCP analysis of the 8th exon is in progress in normal controls. Furthermore, we developed a rapid and convenient method to diagnose the CGG repeat expansion by PCR amplification and ethidium bromide staining of its products. Although behavioral or learning disorders vere shown to be very rarely associated with the CGG repeat expansion, it remains to be determined whether partial deletions or point mutations of the FMR-1 gene could be a cause of these deveopmental disorders.
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