GATA3 abnormalities in six patients with HDR syndrome

Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
Endocrine Journal (Impact Factor: 2). 02/2011; 58(2):117-21. DOI: 10.1507/endocrj.K10E-234
Source: PubMed


GATA3 mutations cause HDR (hypoparathyroidism, sensorineural deafness, and renal dysplasia) syndrome and, consistent with the presence of the second DiGeorge syndrome locus (DGS2) proximal to GATA3, distal 10p deletions often leads to HDR and DiGeorge syndromes. Here, we report on six Japanese patients with GATA3 abnormalities. Cases 1-5 had a normal karyotype, and case 6 had a 46,XX,del(10)(p15) karyotype. Cases 1-6 had two or three of the HDR triad features. Case 6 had no DiGeorge syndrome phenotype except for hypoparathyroidism common to HDR and DiGeorge syndromes. Mutation analysis showed heterozygous GATA3 mutations in cases 1-5, i.e., c.404-405insC (p.P135fsX303) in case 1, c.700T>C & c.708-709insC (p.F234L & p.S237fsX303) on the same allele in case 2, c.737-738insG (p.G246fsX303) in case 3, c.824G>T (p.W275L) in case 4, and IVS5+1G>C (splice error) in case 5. Deletion analysis of chromosome 10p revealed loss of GATA3 and preservation of D10S547 in case 6. The results are consistent with the previous finding that GATA3 mutations are usually identified in patients with two or three of the HDR triad features, and provide supportive data for the mapping of DGS2 in the region proximal to D10S547.

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Available from: Koji Muroya, Dec 19, 2013
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    • "However, there are no clear genotype-phenotype correlations for HDR (Adachi et al., 2006; Zahirieh et al., 2005). Rather, there is a substantial amount of intrafamilial variation, which has been suggested to possibly be due to genetic background effects (Fukami et al., 2011; Hernández et al., 2007; Mino et al., 2005; Nakamura et al., 2011; Zahirieh et al., 2005). However, the cause of this variation is still unknown. "
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    • "Loss of chromosome region 10p13–14 has been described in patients with DGSII, characterized by the presentation of heart defects and T-cell deficiency [Schuffenhauer et al., 1995; Daw et al., 1996; Dasoiuki et al., 1997; Lichtner et al., 2000]. Similarly, haploinsufficiency of the region 10p14 ] pter, distal to DGCR2, results in hypoparathyroidism, sensorineural deafness and renal anomaly, features that determine the HDR syndrome [Van Esch et al., 2000; Fukami et al., 2011]. In this region, it has been described that the GATA3 gene, which is involved in the embryonic development of the parathyroids, auditory system and kidneys, plays a critical role in the development of different neural populations within the mammalian central nervous system [Van Esch et al., 2000; Karunaratne et al., 2002; Lindstrand et al., 2010]. "
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