Preferred Label : Digeorge syndrome/velocardiofacial syndrome complex 2;
CISMeF acronym : DGS2;
Type : Phenotype or locus, molecular basis unknown;
Alternative titles and symbols : DGS2;
Description : The DiGeorge syndrome (DGS; 188400) and velocardiofacial syndrome (VCFS; 192430) may
present many clinical problems, including cardiac defects, hypoparathyroidism, T-cell
immunodeficiency, and facial dysmorphism. They are frequently associated with deletions
within 22q11.2 (accounting in part for the designation CATCH22), but a number of cases
have no detectable molecular defect of this region. Daw et al. (1996) stated that
a number of single case reports with deletions of 10p suggested genetic heterogeneity
of DGS. They compared the regions of hemizygosity in 4 patients with terminal deletions
of 10p (1 patient with hypoparathyroidism and 3 with DGS) and 1 patient with VCFS
and a large interstitial deletion. Fluorescence in situ hybridization (FISH) analysis
demonstrated that these patients had overlapping deletions at the 10p13/10p14 boundary.
A YAC contig spanning the shortest region of deletion overlap (SRO) was assembled
and allowed the size of the SRO to be approximated to 2 Mb. As with deletions of 22q11,
phenotypes varied considerably between affected patients. Daw et al. (1996) concluded
that the results strongly support the hypothesis that haploinsufficiency of a gene
or genes within 10p (DGS2 locus) can cause the DGS/VCFS spectrum of malformations.
Schuffenhauer et al. (1998) performed FISH and PCR analyses in 12 patients with 10p
deletions, 9 of them with features of DGS, and in a familial translocation 10p;14q
associated with midline defects. The critical DGS2 region was defined by 2 DGS patients
and mapped within a 1-cM interval including D10S547 and D10S585. The other 7 DGS patients
were hemizygous for both loci. The breakpoint of the reciprocal translocation 10p;14q
mapped at a distance of at least 12 cM distal to the critical DGS2 region. Interstitial
and terminal deletions described in these patients were in the range of 10 to 50 cM
and enabled the tentative mapping of loci for ptosis and hearing loss, features that
are not part of the DGS clinical spectrum. Bartsch et al. (1999) sought evidence for
chromosomal microdeletions at 10p14-p13 in patients with the DGS/VCFS phenotype. In
a series of patients studied in Dresden, all with normal karyotypes, 22q11 microdeletions
were found in 12, and no patient was found to have a deletion of the critical region
of 10p. Another series studied in Munich included 22 patients with an unequivocal
diagnosis of DGS and no detectable deletion of 22q11. These patients had at least
2 of the 3 major DGS signs: conotruncal heart defect, T-cell deficiency, and hypocalcemia/hypoparathyroidism.
FISH analysis showed a dizygous pattern in all of the patients, indicating no deletions
at the 10p critical region. On the basis of this study, Bartsch et al. (1999) suggested
that;
Prefixed ID : %601362;
Origin ID : 601362;
UMLS CUI : C1832431;
Currated CISMeF NLP mapping
- ORDO concept(s)
- Semantic type(s)
- UMLS correspondences (same concept)
