Scholarlink

Background <p>To improve the precision of molecular diagnosis by means of a comprehensive bidirectional phenotypic and genotypic reanalysis in cases of unresolved monogenic diabetes previously investigated using a targeted next-generation sequencing (tNGS) panel.</p> Methods <p>Molecular and clinical data from 128 unresolved cases referred between 2011 and 2019 were analyzed. These included 92 cases of suspected maturity-onset diabetes of the young (MODY), 12 of neonatal diabetes, 16 of familial partial lipodystrophy (FPLD), 7 of mitochondrial diabetes, and 1 of Wolfram syndrome. All cases were initially investigated using a tNGS panel consisting of 51 nuclear genes and the complete mitochondrial genome.</p> Results <p>This extensive reanalysis process increases molecular diagnosis from 9 to 22%. Phenotypic reevaluation, entailing in-depth phenotyping, is instrumental in excluding 62 atypical cases (48.4%). Genotypic reanalysis identifies 5 previously overlooked molecular defects: two mutations in regulatory regions (one in the <i>HNF1A</i> promoter and another in the <i>PTF1A</i> enhancer); one in the <i>MTTK</i> mitochondrial gene; one in the <i>MFN2</i> gene; and one in the <i>GCK</i> gene.</p> Conclusions <p>Our findings indicate that a combined approach of genotypic and, mainly, phenotypic reanalysis is an effective strategy for improving the accuracy of molecular diagnosis in individuals with suspected monogenic diabetes.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Enhancing the diagnostic yield of monogenic diabetes in unresolved cases with early-onset hyperglycemia

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月24日

查看全文
  • Pedro Campos Franco,
  • Augusto Cezar Santomauro Jr,
  • Aline Dantas Costa-Riquetto,
  • Lucas Santos de Santana,
  • Larissa Garcia Gomes,
  • Alexander Augusto de Lima Jorge,
  • Milena Gurgel Teles

摘要

Background

To improve the precision of molecular diagnosis by means of a comprehensive bidirectional phenotypic and genotypic reanalysis in cases of unresolved monogenic diabetes previously investigated using a targeted next-generation sequencing (tNGS) panel.

Methods

Molecular and clinical data from 128 unresolved cases referred between 2011 and 2019 were analyzed. These included 92 cases of suspected maturity-onset diabetes of the young (MODY), 12 of neonatal diabetes, 16 of familial partial lipodystrophy (FPLD), 7 of mitochondrial diabetes, and 1 of Wolfram syndrome. All cases were initially investigated using a tNGS panel consisting of 51 nuclear genes and the complete mitochondrial genome.

Results

This extensive reanalysis process increases molecular diagnosis from 9 to 22%. Phenotypic reevaluation, entailing in-depth phenotyping, is instrumental in excluding 62 atypical cases (48.4%). Genotypic reanalysis identifies 5 previously overlooked molecular defects: two mutations in regulatory regions (one in the HNF1A promoter and another in the PTF1A enhancer); one in the MTTK mitochondrial gene; one in the MFN2 gene; and one in the GCK gene.

Conclusions

Our findings indicate that a combined approach of genotypic and, mainly, phenotypic reanalysis is an effective strategy for improving the accuracy of molecular diagnosis in individuals with suspected monogenic diabetes.