TULIP1 (RALGAPA1) haploinsufficiency with brain development delay
| Autor: | Toru Higashinakagawa, Mayu Ohtsu, Yu-ichi Goto, Hirokazu Oguni, Toshiyuki Yamamoto, Kousaku Ohno, Eiji Nakagawa, Keiko Shimojima, Yuta Komoike, Jun Tohyama, Sonoko Takahashi, Makiko Osawa, Marco T. Páez |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Male
Candidate gene Developmental delay Developmental Disabilities Molecular Sequence Data Mutation Missense Nerve Tissue Proteins medicine.disease_cause Intellectual Disability medicine Genetics Missense mutation Animals Humans Amino Acid Sequence Child Codon Gene Zebrafish Conserved Sequence Chromosomes Human Pair 14 Gene knockdown Mutation TULIP1 (RALGAPA1) Epilepsy biology Sequence Homology Amino Acid GTPase-Activating Proteins Brain Zebrafish Proteins biology.organism_classification Phenotype Pedigree Chromosomal deletion Gene Knockdown Techniques Muscle Hypotonia Epilepsy Generalized Female Chromosome Deletion Haploinsufficiency Sequence Alignment Human |
| Zdroj: | Genomics. (6):414-422 |
| ISSN: | 0888-7543 |
| DOI: | 10.1016/j.ygeno.2009.08.015 |
| Popis: | A novel microdeletion of 14q13.1q13.3 was identified in a patient with developmental delay and intractable epilepsy. The 2.2-Mb deletion included 15 genes, of which TULIP1 (approved gene symbol: RALGAPA1)was the only gene highly expressed in the brain. Western blotting revealed reduced amount of TULIP1 in cell lysates derived from immortalized lymphocytes of the patient, suggesting the association between TULIP1 haploinsufficiency and the patient's phenotype, then 140 patients were screened for TULIP1 mutations and four missense mutations were identified. Although all four missense mutations were common with parents, reduced TULIP1 was observed in the cell lysates with a P297T mutation identified in a conserved region among species. A full-length homolog of human TULIP1 was identified in zebrafish with 72% identity to human. Tulip1 was highly expressed in zebrafish brain, and knockdown of which resulted in brain developmental delay. Therefore, we suggest that TULIP1 is a candidate gene for developmental delay. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|