Renal cysts and diabetes syndrome linked to mutations of the hepatocyte nuclear factor-1β gene: Description of a new family with associated liver involvement

Montoli, Alberto; Colussi, Giacomo; Massa, Ornella; Caccia, Roberta; Rizzoni, Gianfranco; Civati, G; Barbetti, Fabrizio

doi:10.1053/ajkd.2002.34538

Cited by 55 publications

(33 citation statements)

References 10 publications

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“…TCF2 adult patients have mild to moderate renal failure in the absence of diabetic nephropathy (18). Moreover, pancreatic atrophy, urogenital abnormalities, abnormal liver enzyme levels, and hyperuricemia are observed in patients with TCF2 mutations (12)(13)(14)19,20). Prenatal forms also were described but only as a case report: Cystic renal dysplasia (8,9,12,16), bilateral hyperechogenic kidneys (14,21), renal agenesis, pelvicaliceal dilation, and multicystic dysplastic kidney (14).…”

mentioning

confidence: 99%

Anomalies of the TCF2 Gene Are the Main Cause of Fetal Bilateral Hyperechogenic Kidneys

Decramer

Parant

Beaufils³

et al. 2007

Journal of the American Society of Nephrology

227

194

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Prenatal discovery of fetal bilateral hyperechogenic kidneys is very stressful for pregnant women and their family, and accurate diagnosis of the cause of the moderate forms of this pathology is very difficult. Hepatocyte nuclear factor-1␤ that is encoded by the TCF2 gene is involved in the embryonic development of the kidneys. Sixty-two pregnancies with fetal bilateral hyperechogenic kidneys including 25 fetuses with inaccurate diagnosis were studied. TCF2 gene anomalies were detected in 18 (29%) of these 62 patients, and 15 of these 18 patients presented a complete heterozygous deletion of the TCF2 gene. Family screening revealed de novo TCF2 anomalies in more than half of the patients. TCF2 anomalies were associated with normal amniotic fluid volume and normal-sized kidneys between ؊2 and ؉2 SD in all patients except for two sisters. Antenatal cysts were detected in 11 of 18 patients, unilaterally in eight of 11. After birth, cysts appeared during the first year (17 of 18), and in patients with antenatal cysts, the number increased and developed bilaterally with decreased renal growth. In these 18 patients, the GFR decreased with longer follow-up and was lower in patients with solitary functioning dysplastic kidney. Heterozygous deletion of the TCF2 gene is an important cause of fetal hyperechogenic kidneys in this study and showed to be linked with early disease expression. The renal phenotype and the postnatal evolution were extremely variable and need a prospective long-term follow-up. Extrarenal manifestations are frequent in TCF2-linked pathologies. Therefore, prenatal counseling and follow-up should be multidisciplinary.

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mentioning

confidence: 99%

Anomalies of the TCF2 Gene Are the Main Cause of Fetal Bilateral Hyperechogenic Kidneys

Decramer

Parant

Beaufils³

et al. 2007

Journal of the American Society of Nephrology

227

194

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“…HNF1β is involved in the transcriptional and functional regulations of the liver, biliary system, kidney, urogenital tract, and pancreatic β-cells [3,4]. Defects of this gene have been described in a small subgroup of patients with MODY, including point mutations and whole gene deletions, with the majority being de novo whole gene mutations [5,6]. The phenotypical spectrum of individuals with HNF1β mutations varies widely.…”

Section: Introductionmentioning

confidence: 99%

Hepatocyte Nuclear Factor 1-β Gene Mutation: Brief Report and Review of Hepatic Involvement

Nowicki¹

2018

ACRI

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“…The age of diagnosis ranges from 12 to 61 years [4]. Genital tract malformations, abnormal liver function, hyperuricaemia and gout are also present in some kindreds [4,7,9,10,11]. Diabetes in these kindreds is classified as maturity-onset diabetes of the young subtype 5 (MODY5) [12].…”

Section: Introductionmentioning

confidence: 99%

“…These include insertion/deletion mutations, missense mutations, nonsense mutations and splice site mutations [1,2,3,4,5,6,7,8,9,10,11,13,14,15].…”

Section: Introductionmentioning

confidence: 99%

Abnormal splicing of hepatocyte nuclear factor-1 beta in the renal cysts and diabetes syndrome

et al. 2004

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Aims/hypothesis. Mutations in the hepatocyte nuclear factor-1 beta (HNF-1β) gene result in disorders of renal development, typically involving renal cysts and early-onset diabetes (the RCAD syndrome/ MODY5). Sixteen mutations have been reported, including three splicing mutations of the intron 2 splice donor site. Because tissues showing abundant expression (kidney, liver, pancreas, gut, lung and gonads) are not easily accessible for analysis in living subjects, it has previously proven difficult to determine the effect of HNF-1β mutations at the mRNA level. This is the aim of the present study. Methods. We have developed a nested RT-PCR assay that exploits the presence of ectopic HNF-1β transcripts in Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines derived from subjects carrying HNF-1β splice site mutations.Results. We report a fourth mutation of the intron 2 splice donor site, IVS2nt+2insT. Sequence analysis of ectopic HNF-1β transcripts showed that both IVS2nt+2insT and IVS2nt+1G>T result in the deletion of exon 2 and are predicted to result in premature termination of the HNF-1β protein. Mutant transcripts were less abundant than the normal transcripts but there was no evidence of nonsense-mediated decay. Conclusions/interpretation. This is the first study to define the pathogenic consequences of mutations within the HNF-1β gene by mRNA analysis. This type of approach is a useful and important tool to define mutational mechanisms and determine pathogenicity.Keywords HNF-1β · Illegitimate transcription · MODY5 · RCAD · RT-PCR · Splicing. Abbreviations: Ct, crossing point · EBV, Epstein-Barr virus · HNF-1β, hepatocyte nuclear factor beta · MODY5, maturity-onset diabetes of the young subtype 5 · NMD, nonsense-mediated decay · RCAD, renal cysts and diabetes syndrome Diabetologia (2004) 47:937-942

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Renal cysts and diabetes syndrome linked to mutations of the hepatocyte nuclear factor-1β gene: Description of a new family with associated liver involvement

Cited by 55 publications

References 10 publications

Anomalies of the TCF2 Gene Are the Main Cause of Fetal Bilateral Hyperechogenic Kidneys

Anomalies of the TCF2 Gene Are the Main Cause of Fetal Bilateral Hyperechogenic Kidneys

Hepatocyte Nuclear Factor 1-β Gene Mutation: Brief Report and Review of Hepatic Involvement

Abnormal splicing of hepatocyte nuclear factor-1 beta in the renal cysts and diabetes syndrome

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