RT Journal Article
SR Electronic
T1 Insights from Molecular Characterization of Adult Patients of Families with Multigenerational Diabetes Mellitus.
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP db170867
DO 10.2337/db17-0867
A1 Pezzilli, Serena
A1 Ludovico, Ornella
A1 Biagini, Tommaso
A1 Mercuri, Luana
A1 Alberico, Federica
A1 Lauricella, Eleonora
A1 Dallali, Hamza
A1 Capocefalo, Daniele
A1 Carella, Massimo
A1 Miccinilli, Elide
A1 Piscitelli, Pamela
A1 Scarale, Maria Giovanna
A1 Mazza, Tommaso
A1 Trischitta, Vincenzo
A1 Prudente, Sabrina
YR 2017
UL http://diabetes.diabetesjournals.org/content/early/2017/10/05/db17-0867.abstract
AB Multigenerational diabetes of the adulthood is a mostly overlooked entity, simplistically comprised in the large basin of type 2 diabetes. The general aim we are pursuing in last years is to unravel the genetic causes of such form of diabetes. Identifying among families with multigenerational diabetes those carrying mutations in known monogenic diabetes genes is the first step to then concentrate on remaining pedigrees where to unravel new diabetogenes.Targeted Next Generation Sequencing of 27 monogenic diabetes-genes has been carried out in 55 family probands and identified mutations verified among their relatives by Sanger sequencing.Nine variants (in 8 probands) survived our filtering/prioritization strategy. After likelihood of causality assessment by established guidelines, 6 variants were classified as “pathogenetic/likely pathogenetic” and 2 as “of uncertain significance”.Combining present with our previous data on the six genes causing the most common forms of maturity-onset diabetes of the young allows inferring that 23.6% families with multigenerational diabetes of the adulthood carry mutations in known monogenic diabetes-genes.Our findings indicate that the genetic background of hyperglycemia is unrecognized in the vast majority of families with multigenerational diabetes of the adulthood. These families now become the object of further research aimed at unraveling new diabetogenes.