2005 Fiscal Year Final Research Report Summary
Isolation and characterization of the new genes isolated from three diseases presenting with severe psychomotor retardation.
| Project/Area Number |
15390332
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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Principal Investigator |
WAKAMATSU Nobuaki Institute for Developmental Research, Aichi Human Service Center, Derpartment of Genetics, Department Head, 遺伝学部, 部長 (60274198)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Yasukazu Institute for Developmental Research, Aichi Human Service Center, Derpartment of Genetics, Division Chief, 遺伝学部, 室長 (70191343)
KUWANO Ryouzo Brain Research Institute, Niigata University, Department of Bioinformatics, Associate Professor, 脳研究所・遺伝子実験部門, 助教授 (20111734)
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| Project Period (FY) |
2003 – 2005
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| Keywords | mental retardation / gene / PLEKHA5 / autosomal recessive / X-linked recessive / brain atrophy |
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| Research Abstract |
1. Isolation of the causal gene from the patient presenting with reciprocal 6q16/12p12 translocation, epilepsy and severe psychomotor retardation.
We identified a new gene, PLEKHA5, at the breaking point of the 12p12 by FISH, Southern blot and nucleotide sequencing analyses. There was no gene located at the 6q16 breaking point. To examine the role of this gene, we transfected Plekha5-speciflc siRNA into mouse Neuro2a cells. Transfected cells express about 40% of Plekha5 mRNA and showed limited extension of the neurites compared to cells undergoing Mock transfection (vector only) when treated with 20 μM retinoic acid. This finding suggests that PLEKHA5 is likely a causal gene of this disease. Plekha5 localized at the cytoplasm. Affinity purified PLEKHA5 showed a size of 130 kDa.
2. Isolation of the causal gene from male patients in a family presenting with severe psychomotor retardation.
We performed linkage analysis in 11 members of the family. Three of these eleven were patients. Maximal
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lod score, 1.10, was obtained at DXS1205 of Xq27. Nucleotide sequencing analysis was performed for 15 candidate genes at Xq27-ter from the patients' DNA, but there were no apparent mutations.
3. Isolation of the causal gene from patients in a family presenting with rapid brain atrophy and severe psychomotor retardation.
We performed linkage analysis in 10 members of the family. Four of these ten were patients. Maximal lod score, 4.75 was obtained between D2S163 and D2S2344 at 2q35-36. Nucleotide sequence analysis was performed for 16 candidate genes and an E320Q missense mutation was found in SLC19A3. The patients were homozygous for the mutation and their parents were heterozygous. We constructed an expression vector pC1-SLC19A3 (E320Q), that expressed SLCJ9A3 (E320Q) driven by a CMV promoter and examined the transporter activity of thiamine and biotin after transfection of this vector into HEK293 cells. However, there was no remarkable reduction of transporter activity. We are now producing transgenic mouse expressing Slc193 (E320Q) to further investigate the effects of this mutation. Less
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Research Products
(35 results)
