Agenesis of the corpus callosum associated with a chromosome (4;14) translocation. D. Kamnasaran1, M. Muenke2, P.C.M. O'Brien3, M.A. Ferguson-Smith3, D.W. Cox1. 1) Medical Genetics, University of Alberta, Edmonton, Alberta, Canada; 2) Children's Hospital of Philadelphia and MBG, NHGRI, NIH, Bethesda, MD, U.S.A; 3) Clinical Veterinary Medicine,Centre for Veterinary Science,Cambridge, U.K.
Disorders such as holoprosencephaly and autosomal dominant and recessive deafness syndromes are associated with the chromosome 14q12-q13 cytogenetic region. We report a proband with a 46,XY,t(4;14)(q25;q13) karyotype who has agenesis of the corpus callosum, microcephaly, low set ears, feeding problems and failure to thrive. We have mapped the proband's translocation breakpoint between the markers AFM200ZH4 and D14S306 on chromosome 14 and between the markers D4S2449 and D4S3167 on chromosome 4 by PCR analysis of flow sorted chromosomes. We have assembled a 3 Mb YAC contig that spans the translocation breakpoint on chromosome 14 by selecting CEPH YAC clones that are positive for markers localized to the interval. This was done in order to map, by PCR, all known genes that have been binned to the 14q13 region and to analyze potential candidate genes. Six known genes, PAX9, TTF1, HNF3A, SEC23, SDK3 and RPS14 mapped onto the YAC contig. Of the genes mapped at the 14q13 translocation breakpoint, TTF1 is a potential candidate for the agenesis of the corpus callosum observed in the proband. We have also analyzed PITX2 at the chromosome 4q25 region as another potential candidate gene for agenesis of the corpus callosum. PITX2 is the gene for Rieger syndrome. A putative deletion within PITX2 was found by PCR analysis of flow sorted chromosomes with primer pairs that amplified different exons of the gene. PITX2 was physically estimated to map at least 1.2 Mb proximal to the translocation breakpoint on chromosome 4 by mapping on CEPH YAC clones binned to 4q25. The presence of two breaks at 4q25 implies a possible inversion at this region.