17q12 microdeletion is the first among chromosomal abnormalities to have been demostrated to cause diabetes and the third to cause renal disease. 17q12 deletion can lead to different clinical features, being characterized by variable expressivity. Renal abnormalities associated with 17q12 microdeletion include bilateral multicystic renal dysplasia, bilateral ureteropelvic junction stenosis and ureteral atresia. When particularly severe, renal abnormalities can be diagnosed in utero by ultrasound. Diabetes is usually a multi-factorial disease, namely determined by the occurrence of multiple genetic and environmental factors. However, 17q12 microdeletion related diabetes is solely genetic, being caused by the functional loss (due to deletion or mutation) of the TCF2 gene, contained in the 17q12 region. This particular type of diabetes is classified as the fifth type of MODY diabetes (and therefore called MODY5; MODY is an acronym for English Maturity Onset Diabetes of the Young and identifies the onset in the youth of the typical diabetes of the adult [non-insulin dependent]).
The TCF2 functional loss, probably coupled with the functional loss of another gene located in the same region, LHX1, is also responsible for kidney disease.
It’s of note that the duplication (and not the deletion) of the 17q12 segment appears to be somewhat different, being basically characterized by epilepsy. Interestingly, 17q12 microdeletion has also been reported to cause around 6% of all Rokitansky syndrome cases (read here for more infromation).
References:
Mefford HC, Clauin S, Sharp AJ, Moller RS, Ullmann R, Kapur R, Pinkel D, Cooper GM, Ventura M, Ropers HH, Tommerup N, Eichler EE, Bellanne-Chantelot C. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. Am J Hum Genet. 2007 Nov;81(5):1057-69. PMID: 17924346
The TCF2 functional loss, probably coupled with the functional loss of another gene located in the same region, LHX1, is also responsible for kidney disease.
It’s of note that the duplication (and not the deletion) of the 17q12 segment appears to be somewhat different, being basically characterized by epilepsy. Interestingly, 17q12 microdeletion has also been reported to cause around 6% of all Rokitansky syndrome cases (read here for more infromation).
References:
Mefford HC, Clauin S, Sharp AJ, Moller RS, Ullmann R, Kapur R, Pinkel D, Cooper GM, Ventura M, Ropers HH, Tommerup N, Eichler EE, Bellanne-Chantelot C. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. Am J Hum Genet. 2007 Nov;81(5):1057-69. PMID: 17924346
