Identification of a novel recessive RELN mutation using a homozygous balanced reciprocal translocation

Cornell University, Итак, New York, United States
American Journal of Medical Genetics Part A (Impact Factor: 2.05). 05/2007; 143A(9):939-44. DOI: 10.1002/ajmg.a.31667
Source: PubMed

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.

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Available from: Joseph Gleeson, Dec 18, 2013
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    • "Reelin deficiency (Reeler) is characterized by an inverted lamination of the neocortex, and the human Reelin (RELN) mutation has been linked to lissencephaly, autism and other disorders (Hong et al., 2000; Zaki et al., 2007). Reelin encodes an extracellular matrixassociated glycoprotein that is secreted by Cajal-Retzius cells in the developing cerebral cortex. "
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    • "In addition, it has been demonstrated that subcortical band heterotopia can be observed in males with somatic mosaic mutations in DCX and in males and female with missense or somatic mosaic mutations in LIS1 (Leventer et al., 2001; d'Agostino et al., 2002; Poolos et al., 2002; Sicca et al., 2003). Homozygous Reelin (RELN) mutations have been identified in four cases of lissencephaly associated with severe cerebellar and pontine hypoplasia (Hong et al., 2000; Chang et al., 2007; Zaki et al., 2007). As yet, no neuropathological data, especially concerning the cortical cytoarchitecture , have been reported for such cases. "
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