Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease.
Summary of "Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease."
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. (c) 2010 Wiley-Liss, Inc.
Division of Pediatric Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
This article was published in the following journal.
Name: American journal of medical genetics. Part A
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20799338
- DOI: http://dx.doi.org/10.1002/ajmg.a.33628
Medical and Biotech [MESH] Definitions
A disorder caused by hemizygous microdeletion of about 28 genes on chromosome 7q11.23, including the ELASTIN gene. Clinical manifestations include SUPRAVALVULAR AORTIC STENOSIS; MENTAL RETARDATION; elfin facies; impaired visuospatial constructive abilities; and transient HYPERCALCEMIA in infancy. The condition affects both sexes, with onset at birth or in early infancy.
Sex Chromosome Disorders
Clinical conditions caused by an abnormal sex chromosome constitution (SEX CHROMOSOME ABERRATIONS) in which there is extra or missing sex chromosome material (either a whole chromosome or a chromosome segment).
Sex Chromosome Disorders Of Sex Development
Congenital conditions of atypical sexual development associated with abnormal sex chromosome constitutions including MONOSOMY; TRISOMY; and MOSAICISM.
Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429)
A preconceived judgment made without adequate evidence and not easily alterable by presentation of contrary evidence.
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