Abstract
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.
Publication types
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Case Reports
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Brain / abnormalities
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Brain / embryology
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Child
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Chromosome Deletion*
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Chromosomes, Human, Pair 14 / genetics*
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Chromosomes, Human, Pair 14 / ultrastructure
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Codon / genetics
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Conserved Sequence
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Developmental Disabilities / genetics*
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Epilepsy, Generalized / genetics*
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Female
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GTPase-Activating Proteins / deficiency*
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GTPase-Activating Proteins / genetics
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GTPase-Activating Proteins / physiology
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Gene Knockdown Techniques
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Humans
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Intellectual Disability / genetics
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Male
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Molecular Sequence Data
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Muscle Hypotonia / genetics
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Mutation, Missense*
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Nerve Tissue Proteins / deficiency*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology
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Pedigree
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Sequence Alignment
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Sequence Homology, Amino Acid
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Zebrafish / embryology
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Zebrafish / genetics
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Zebrafish Proteins / deficiency
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Zebrafish Proteins / genetics
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Zebrafish Proteins / physiology
Substances
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Codon
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GTPase-Activating Proteins
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Nerve Tissue Proteins
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RALGAPA1 protein, human
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RALGAPA1 protein, zebrafish
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Zebrafish Proteins