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Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease
Author(s) -
Sampson Matthew G.,
Coughlin Curtis R.,
Kaplan Paige,
Conlin Laura K.,
Meyers Kevin E.C.,
Zackai Elaine H.,
Spinner Nancy B.,
Copelovitch Lawrence
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33628
Subject(s) - renal agenesis , hirschsprung's disease , medicine , urinary system , vesicoureteral reflux , kidney disease , kidney , kidney development , disease , agenesis , pathology , gastroenterology , genetics , biology , gene , reflux , anatomy , embryonic stem cell
Congenital Anomalies of the Kidney and Urinary Tract can be associated with Hirschsprung disease. We report on three children with a similar 16p11.2 microdeletion with a spectrum of clinical anomalies consisting of congenital anomalies of the kidney and urinary tract in two patients (Patients 1 and 2) and Hirschsprung disease in two patients (Patients 1 and 3), leading us to hypothesize that a gene in this region is associated with these phenotypes. Patient 1 presented with left renal agenesis, grade‐IV vesicoureteral reflux, and Hirschsprung disease, Patient 2 with left renal agenesis, chronic kidney disease, chronic constipation, seizures, and developmental delay, and Patient 3 with Hirschsprung disease and normal kidneys. Genome‐wide microarray analysis demonstrated overlapping microdeletions within 16p11.2. The shortest region of overlap in the three patients contained only eight genes, including the SH2 domain‐containing binding protein 1 ( SH2B1 ), an adaptor protein which has been implicated in enhancement of the tyrosine kinase activity of RET, whose role in developmental disease of the kidney and enteric enervation is well established. Our findings suggest that 16p11.2 deletions are associated with abnormalities of renal and enteric development and we hypothesize that deletion of SH2B1 may account for the observed phenotype. © 2010 Wiley‐Liss, Inc.