Case Report 10p12.1 deletion: HDR phenotype without DGS2 features Elisa Benetti a, ⁎, Luisa Murer a,b , Andrea Bordugo c , Barbara Andreetta a , Lina Artifoni b a Pediatric Nephrology, Dialysis and Transplantation Unit, Department of Pediatrics, University of Padua, Via Giustiniani, 3, 35128 Padua, Italy b Laboratory of Pediatric Nephrology, Department of Pediatrics, University of Padua, Italy c Department of Pediatrics, Ospedale Santa Maria degli Angeli, Pordenone, Italy abstract article info Article history: Received 21 October 2008 Available online 31 October 2008 Keywords: GATA3 gene HDR syndrome DiGeorge syndrome Chromosome deletion 10p chromosome Gene deletion Renal hypodysplasia Deafness Hypoparathyroidism Chronic renal failure GATA3 gene encodes a transcription factor expressed during thymus, liver, kidney, adrenal gland, central and peripheral nervous systems, placenta and T lymphocytes embryonic development. Mutations of GATA3 cause Hypoparathyroidism, sensorineural Deafness and Renal dysplasia syndrome (HDR). We report the case of a girl with a terminal deletion of the short arm of chromosome 10 (10p12.1-pter), including both HDR locus and the DiGeorge critical region 2 (DGCR2), with HDR phenotype but not DiGeorge syndrome 2 features. The girl developed chronic renal failure during the first year of life, associated with sensorineural hearing loss, facial dysmorphic features and psychomotor development. She had hypodysplastic kidneys and bilateral grade 3-vesicoureteric reflux. Her karyotype was 46,XX,del(10)(p12.1-pter). Quantitative analysis by Real Time PCR on blood DNA confirmed the lack of one copy of GATA3 gene. She underwent renal transplantation at the age of 11. Our patient is the first case with a large deletion of the short arm of chromosome 10 - that certainly involves DGCR2 - with the HDR phenotype but without the clinical features of DGS2. This peculiarity suggests the hypothesis that the mechanisms underlying this syndrome may be more complex. It is therefore possible that DGS2 may be determined by locus heterogeneity. © 2008 Elsevier Inc. All rights reserved. Introduction GATA3 gene localizes on 10p14-15 and is a transcription factor belonging to a family of six zinc fingers-proteins that are involved in different organs development. In animal models, gata3 is expressed during thymus, liver, kidney, adrenal gland, central and peripheral nervous systems, placenta and T lymphocytes embryonic develop- ment. In humans, GATA3 plays an important role in T lymphocytes differentiation by activating genes for the CD8alfa chain and for T-cells receptors, but it is also involved in kidney, inner ear, parathyroids and central nervous system embryogenesis. In adults, its expression is restricted to T lineage (Debacker et al., 1999). In kidney development, GATA3 is expressed in the mesonephros from the 4th week of gesta- tion (WG). In the metanephros, the gene is intensely expressed in the ureteric bud (UB) from the 7th WG, when the Wolffian duct has penetrated into the metanephric blastema and ureteric branching and mesenchymal differentiation occur. Later, GATA3 expression remains high in the UB and in epithelial cells of the collecting duct until the 32nd WG (Labastie et al., 1995). Mutations or deletions of GATA3 cause Hypoparathyroidism, sen- sorineural Deafness and Renal dysplasia syndrome (HDR; MIM 146255), an autosomal dominant disorder, characterized by hypopara- thyroidism, moderate to severe bilateral sensorineural hearing loss and various renal anomalies, including renal hypoplasia/dysplasia, pelvicalyceal deformity and vesicoureteral reflux. HDR was also reported in patients who carried 10p deletions and showed clinical features of DiGeorge Syndrome (DGS). Thus a DiGeorge-like (DGS2) locus was placed on 10p13-14 and called DiGeorge Critical Region 2 (Lichtner et al., 2000; Hernández et al., 2007). Herein we report the case of a girl with a terminal deletion of the short arm of chromosome 10, resulting in a complete haploinsuffi- ciency of GATA3 gene, with HDR phenotype but not DGS2 features. Case report The girl was delivered at term after caesarean section for podalic presentation. Ultrasound examinations during her prenatal course showed intrauterine growth restriction and decreased fetal move- ments since the 5th week of gestation (WG). Her birth weight and length were 2160 g and 44 cm respectively (both b 3rd percentile), but head circumference was 34 cm (50th percentile). Family history was non-contributory. During the first weeks of life, she presented feeding difficulties with poor weight gain and recurrent respiratory tract infections. At the age of 8 months, she was admitted to another hospital to undergo an evaluation for three urinary tract infection episodes. Physical Experimental and Molecular Pathology 86 (2009) 74–76 ⁎ Corresponding author. Fax: +39 0498211401. E-mail address: elisabene@libero.it (E. Benetti). 0014-4800/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.yexmp.2008.10.003 Contents lists available at ScienceDirect Experimental and Molecular Pathology journal homepage: www.elsevier.com/locate/yexmp