Abstract for presentation at 11th International Congress of Human Genetics

Investigating DiGeorge-like deletions on chromosome 10p using probes for GATA3 and NEBL

  • Art Daniel, Cytogenetics, WSGP, Children's Hospital at Westmead, Sydney, Australia., Australia
  • Sally Byatt, Cytogenetics, WSGP, Children's Hospital at Westmead, Sydney, Australia., Australia
  • Meredith Wilson, Clinical Genetics, WSGP, Children's Hospital at Westmead., Australia
  • Felicity Collins, Clinical Genetics, WSGP, Children's Hospital at Westmead., Australia
  • Nicole Graf, Histopathology, Children's Hospital at Westmead., Australia

    • In addition to the typical VCFS syndrome associated with del(22q), two rare DiGeorge-like syndromes have been described due to partial deletion of chromosome 10p. These are: HDR syndrome (hypoparathyroidism, sensorineural deafness, renal malformations; OMIM 146255)is associated with the distal deletion along with the candidate gene GATA3 and a location within 10p14-15.1. DiGeorge syndrome 2(congenital heart defects, T cell immune deficiency, hypoparathyroidism/hypocalcemia, facial anomalies, developmental and growth retardation; OMIM 601362)is associated with a proximal deletion along with the candidate gene NEBL and a presumed location within 10p13-14. The actual location for NEBL is at 10p12.31 (21.0 Mb from pter) and this is 9.8 Mb more proximal to the former critical region for DGS on 10p near D10S585 (11.2 Mb from pter). We describe the findings in two patients with chromosomal deletion 10p for which FISH probes of the two candidate genes were developed. Case 1 (fetally diagnosed proband) had the GATA3 gene(RP11-379F12)deleted, the NEBL gene (RP11-56H7)intact and Case 2 (a girl of 11 yrs)had the reverse. Case 2 had partial DGS: she was small with WT <10th centile; length <3rd centile; abnormal facies; partial T cell deficiency; moderate VSD, ASD and intellectual disability; but normal serum calcium levels. The two 10p deletions were mapped with microsatellites. From the latter data, the 10p deletion of Case 1 with the deleted GATA3(locus in 10p14) had deleted paternal alleles for D10S249; S1745; S591; S189, and S1649. Case 2 with the NEBL deletion had deleted maternal alleles for D10S191; S1653; and S548, mapping by microsatellites to 10p12-13 and previously by cytogenetics to 10p12-13. These data taken together with the locus of NEBL at 10p12.31 suggest DGS2 has a more proximal location than previously thought. A prenatal diagnosis (normal result & outcome) jointly using these two probes was performed in a subsequent pregnancy for the parents of Case 1.

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