Abstract
Two siblings from a consanguineous Egyptian marriage showed an identical phenotype of cortical lissencephaly with cerebellar hypoplasia, severe epilepsy, and mental retardation. Examination of karyotype revealed 46, t(7;12)(q22;p13)mat (7;12)(q22;p13)pat in both affected children, suggesting a homozygous reciprocal balanced translocation. Each healthy parent was a carrier of the balanced translocation in the heterozygous state, suggesting homozygous disruption of a gene involved in brain development. There were early spontaneous abortions in this family, as would be expected from transmission of an unbalanced chromosome. A disruption of RELN at 7q22.1 with absence of encoded protein was identified. This is the first demonstration that such rare homozygous translocations can be used to identify recessive disease gene mutations.
Publication types
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Case Reports
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Abnormalities, Multiple / diagnosis
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Abnormalities, Multiple / genetics
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Brain / abnormalities
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Brain Diseases / genetics
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Cell Adhesion Molecules, Neuronal / genetics*
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Child, Preschool
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Chromosome Banding
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Epilepsy / genetics
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Extracellular Matrix Proteins / genetics*
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Female
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Genes, Recessive*
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Homozygote
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Humans
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Intellectual Disability / genetics
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Male
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Mutation*
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Nerve Tissue Proteins / genetics*
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Pedigree
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Receptor Protein-Tyrosine Kinases / genetics
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Reelin Protein
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Serine Endopeptidases / genetics*
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Translocation, Genetic*
Substances
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Cell Adhesion Molecules, Neuronal
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Extracellular Matrix Proteins
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Nerve Tissue Proteins
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Reelin Protein
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Receptor Protein-Tyrosine Kinases
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TYRO3 protein, human
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RELN protein, human
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Serine Endopeptidases