Prenatal diagnosis of HNF1b mutation allows recognition of neonatal dysglycemia
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CASE REPORT
Prenatal diagnosis of HNF1b mutation allows recognition of neonatal dysglycemia Fernanda Iafusco1,2 · Serena Meola1,2 · Carmine Pecoraro3 · Cristina Mazzaccara1,2 · Dario Iafusco4 · Nadia Tinto1,2 Received: 28 September 2020 / Accepted: 16 November 2020 © The Author(s) 2020
Keywords Prenatal diagnosis · Maturity onset diabetes of the young (MODY) · Neonatal HNF1b dysglycemia
Introduction Maturity onset diabetes of the young (MODY) is the most common form of monogenic diabetes in Europe, affecting between 1 and 6% of diabetic patients. It comprises a group of heterogeneous genetic disorders characterized by early onset of diabetes (commonly before age 25), absence of autoimmunity, and beta-cell dysfunction. So far, mutations in 14 different genes involved in glucose homeostasis and pancreatic development [1] have been associated with this disease. Although it is an autosomal dominant disorder, de novo mutations should be taken into consideration in patients without a family history of diabetes. Most cases of MODY are due to mutations in GCK, HNF1a, HNF4a and HNF1b, previously known as MODY2, MODY3, MODY1, and MODY5, respectively. Among these, HNF1b is an active transcription factor that forms homodimers or heterodimers with HNF1a and plays a fundamental role in kidney development, nephron differentiation, and pancreatic growth and differentiation. Mutations in this gene lead to congenital anomalies of the kidney and urinary tract, genital malformations, pancreatic atrophy with endocrine and exocrine deficiency [2]. Diabetes usually onsets in early adulthood and frequently requires insulin treatment. Managed by Antonio Secchi. * Nadia Tinto [email protected] 1
Department of Molecular Medicine and Medical Biotechnology, University “Federico II”, Naples, Italy
2
CEINGE Advanced Biotechnology, Naples, Italy
3
Nephrologist Unit, Santobono Children’s Hospital, Naples, Italy
4
Department of Pediatrics, University of Campania “Luigi Vanvitelli”, Naples, Italy
We present an unusual case of a prenatal diagnosis that revealed a mutation in the HNF1b gene responsible for neonatal hyperglycemia in a pregnant woman affected by X-linked ectodermal dysplasia.
Case report We describe the case of a 30-year-old pregnant woman affected by incontinentia pigmenti, a rare multisystemic ectodermal dysplasia with X-linked dominant inheritance. 16 weeks into her first pregnancy, she underwent amniocentesis to find out whether her fetus had inherited the disease. Although fetal DNA resulted negative for the maternal disease, the fetal anatomy ultrasound showed severe renal abnormalities, namely, increased echogenicity of the renal parenchyma and bilateral kidney enlargement. Accordingly, we performed a clinical exome analysis by Next Generation Sequencing (NGS) (Illumina Next-Seq500) including about 5000 disease-associated genes and limited the bioinformatics analysis to HNF1b, PKD1, PKD2, PKHD1 genes associated with renal cysts to identify the genetic cause of the kidney alterations. A heterozygous nucle
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