Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.3.1.51 (HDR)
 605 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Partial monosomy 10p is a rare chromosomal condition and a significant proportion of patients show features of DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS). A critical haploinsufficiency region for DGS/VCFS was defined on 10p (DGCR2). We performed molecular deletion analysis of two further patients with partial monosomy 10p, who showed hypoparathyroidism, deafness, and renal dysplasia or renal insufficiency, but no cardiac defect, cleft palate, or reduced T cell levels. Previously, the combination of hypoparathyroidism, deafness, and renal dysplasia has been proposed to represent a specific syndrome (MIM 146255) under the acronym HDR. In addition to the two patients in this report, at least four published cases with partial monosomy 10p show the triad of HDR and 14 other patients present with at least two of the three features. We therefore conclude that HDR syndrome can be associated with partial monosomy 10p. Based on molecular deletion analysis and the clinical data, we suggest that the DGS/VCFS phenotype associated with 10p deletion can be considered as a contiguous gene syndrome owing to haploinsufficiency of two different regions. Hemizygosity of the proximal region, designated DGCR2, can cause cardiac defect and T cell deficiency. Hemizygosity of the distal region, designated HDR1, can cause hypoparathyroidism and in addition sensorineuronal deafness and renal dysplasia/insufficiency or a subset of this triad.
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PMID:An HDR (hypoparathyroidism, deafness, renal dysplasia) syndrome locus maps distal to the DiGeorge syndrome region on 10p13/14. 1063 31

Partial monosomy 10p is a rare chromosomal aberration. Patients often show symptoms of the DiGeorge/velocardiofacial syndrome spectrum. The phenotype is the result of haploinsufficiency of at least two regions on 10p, the HDR1 region associated with hypoparathyroidism, sensorineural deafness, and renal defects (HDR syndrome) and the more proximal region DGCR2 responsible for heart defects and thymus hypoplasia/aplasia. While GATA3 was identified as the disease causing gene for HDR syndrome, no genes have been identified thus far for the symptoms associated with DGCR2 haploinsufficiency. We constructed a deletion map of partial monosomy 10p patients and narrowed the critical region DGCR2 to about 300 kb. The genomic draft sequence of this region contains only one known gene, BRUNOL3 ( NAPOR, CUGBP2, ETR3). In situ hybridization of human embryos and fetuses revealed as well as in other tissues a strong expression of BRUNOL3 in thymus during different developmental stages. BRUNOL3 appears to be an important factor for thymus development and is therefore a candidate gene for the thymus hypoplasia/aplasia seen in partial monosomy 10p patients. We did not find BRUNOL3 mutations in 92 DiGeorge syndrome-like patients without chromosomal deletions and in 8 parents with congenital heart defect children.
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PMID:Expression and mutation analysis of BRUNOL3, a candidate gene for heart and thymus developmental defects associated with partial monosomy 10p. 1211 Sep 49

Haploinsufficiency of a region located distal to 10p14 designated HDR1, is responsible for hypoparathyroidism, sensorineural deafness, and renal anomalies (HDR syndrome). Haploinsufficiency of a more proximal region, located on 10p13-10p14, designated as DGCR2 is associated with congenital heart defects and thymus hypoplasia/aplasia or T cell defect. We describe a patient showing facial dysmorphisms, delayed psychomotor development and bilateral sensorineural hearing loss and carrying a 10p14 deletion, the smallest deletion found in the literature so far. Our patient, carrying a partial deletion of the DGCR2 region and of the HDR1 region, including the GATA3 gene, showed, unexpectedly, only few of the clinical features of DiGeorge 2 syndrome (psychomotor retardation, palpebral ptosis, epicanthic folds, anteverted nares, cryptorchidism, hand/foot abnormalities) and did not show other typical signs, such as cardiac defect, cleft palate, and abnormal T cell levels. Of the three characteristic features of the HDR syndrome, our patient had only sensorineural deafness. On the basis of the revision of the other cases reported in the literature with a deletion including the 10p14 region, we suggest that GATA3 haploinsufficiency, although not recorded for each patient, is responsible for deafness. The present case shows that even this small 10p deletion is responsible for a specific phenotype. We also underline the importance of CGH-array, in order to obtain a more precise physical mapping of the 10p deletions and an accurate genotype-phenotype correlation.
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PMID:Clinical description of a patient carrying the smallest reported deletion involving 10p14 region. 2240 89