Lerer et al. (2005) described a nonconsanguineous 4-generation Israeli family of Jewish Moroccan origin in which 9 children were affected with a congenital neurodegenerative disease resembling cerebral palsy. Congenital hypotonia evolved over the first year to spastic quadriplegia ... Lerer et al. (2005) described a nonconsanguineous 4-generation Israeli family of Jewish Moroccan origin in which 9 children were affected with a congenital neurodegenerative disease resembling cerebral palsy. Congenital hypotonia evolved over the first year to spastic quadriplegia with accompanying transient nystagmus. All affected individuals had varying degrees of mental retardation. Neuroimaging studies showed brain atrophy and ventriculomegaly. No biochemical abnormalities were detected. All affected children were born to related clinically healthy fathers, indicating that inheritance was dependent on parental gender.
Using segregation analysis, Southern hybridization, and long-range PCR, Lerer et al. (2005) identified a 225-kb deletion at chromosome 9p24 in affected and carrier members of the 4-generation family with a cerebral palsy-like disorder studied by them. The ANKRD15 ... Using segregation analysis, Southern hybridization, and long-range PCR, Lerer et al. (2005) identified a 225-kb deletion at chromosome 9p24 in affected and carrier members of the 4-generation family with a cerebral palsy-like disorder studied by them. The ANKRD15 (ankyrin repeat domain-15) gene was found to be the only gene within the deletion. The DOCK8 gene (611432) is located telomeric to the ANKRD15 gene, and the DMRT1 gene (602424) lies on the centromeric side. RT-PCR of lymphoblastoid cell lines established from affected individuals and their fathers revealed very little expression of the 2 variants of ANKRD15 in affected individuals, whereas in carrier fathers expression was similar to that in normal controls, suggesting monoalleic expression of the paternal allele. In an analysis of the methylation patterns of CpG islands in the promoter region of the ANKRD15 gene, no differences were found between affected individuals, their fathers, and controls. However, differences in methylation pattern were found in the promoter region of the DMRT1 gene. Hypermethylation occurred only on the deleted chromosome when it was transmitted through the mother (to carrier fathers), but upon paternal transmission (to affected children) this region was hypomethylated, as in individuals without deletion. Lerer et al. (2005) concluded that the deletion itself created an imprinting effect.