Mutations in the HNF1B gene cause MODY5
, which in affected individuals is associated with early-onset diabetes and also urogenital and renal pathology.
Selected Examples of Genes in Which Mutations can Result in Various Congenital Abnormalities of the Kidney and Urinary Tract (CAKUT) Lesions CAKUT PAX2 TCF2 EYA1 SIX1 SALL1 Dysplasia X XX XX Agenesis X X Hypoplasia X X X UPJ obst X X X VU reflux X GCKD X Syndrome Renal-coloboma MODY5
BOR BOR Townes-Brock CAKUT GATA3 Dysplasia X Agenesis X Hypoplasia UPJ obst VU reflux X GCKD Syndrome HDR Abbreviations: BOR, branchial-oto-renal syndrome; GCKD, glomerulocystic kidney disease; HDR, hypoparathyroidism, deafness and renal dyspla- sia; MODY, maturity onset diabetes type 5; UPJ obst, ureteropelvic junction obstruction; VU, vesicoureteral.
A significant fraction of prenatally detected, neonatal, and pediatric renal structural abnormalities are caused by complete or partial deletions of the TCF2 gene (also called HNF1B), which can also cause maturityonset (or MODY5
Genetic defects in six genes are known to cause MODY: the hepatocyte nuclear factor-4[alpha]: HNF-4[alpha]/(MODY1); glucokinase: GCK/(MODY2); the hepatocyte nuclear factor-1[alpha]: HNF-1[alpha]/(MODY3); insulin promoter factor-1: IPFl/ (MODY4); hepatocyte nuclear factor-1[beta]: HNF-1[beta]/(MODY5
); and transcriptional factor, neurogenic differentiation1: Neuro-D1/(MODY 6) (3-5).
In addition to small kidneys with irregular enlarged collecting systems or absent calices, and occasional Mullerian tract malformations in females, affected families also have maturity-onset diabetes mellitus of the young (MODY5; MIM 604284).
(154) The typical inheritance pattern and associations, for example, maturity-onset diabetes of the young (MODY5), severe pancreatic hypoplasia, or pyelocalyceal abnormalities can be very helpful in this setting (Figure 8).