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A Hirschsprung disease locus at 22q11?
W S Kerstjens-Frederikse1, R M Hofstra, A J van Essen
1Department of Medical Genetics, University of Groningen, The Netherlands.
Journal of Medical Genetics
|April 16, 1999
Summary
A deletion in chromosome 22q11.2 is linked to Hirschsprung disease (HSCR) and velocardiofacial syndrome in a patient. This suggests a gene in this region may be crucial for enteric nervous system development.
Area of Science:
- Genetics
- Developmental Biology
- Pediatrics
Background:
- Hirschsprung disease (HSCR) is a congenital disorder affecting the enteric nervous system.
- Velocardiofacial syndrome (VCFS) and DiGeorge syndrome are associated with deletions in chromosome 22q11.2.
- The genetic basis for the co-occurrence of HSCR and VCFS is not fully understood.
Observation:
- A pediatric patient presented with truncus arteriosus, dysmorphic features, developmental delay, hypotonia, short segment HSCR, and paroxysmal hypoventilation.
- Fluorescence in situ hybridization (FISH) analysis revealed an interstitial deletion in chromosome band 22q11.2.
- Genetic screening of known HSCR-associated genes (RET, GDNF, EDNRB, EDN3) did not identify any mutations.
Findings:
- The patient's 22q11.2 deletion overlaps with deletions characteristic of DiGeorge syndrome and velocardiofacial syndrome.
- The absence of mutations in known HSCR genes, coupled with the 22q11.2 deletion, points to a novel genetic etiology.
- Two additional patients with velocardiofacial syndrome and HSCR were identified, strengthening the association.
Implications:
- The 22q11.2 region may harbor a gene essential for enteric nervous system development, implicated in the pathogenesis of HSCR in VCFS patients.
- This finding could lead to improved genetic diagnostics and counseling for individuals with 22q11.2 deletions.
- Further research into the 22q11.2 region is warranted to identify the specific gene(s) responsible for HSCR in this context.