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

Abstract

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.

Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides

“…42 Mutations in HNF-1b result in renal cysts and congenital kidney anomalies. 43 In addition, during AKI, HNF-1b regulated the expression of genes important for homeostasis control, repair, and the state of epithelial cell differentiation. 44 A shortcoming of our study is the fact that we could not obtain detailed data on the probable cause of CKD for all patients (we obtained the probable cause of CKD for 91.4% of the patients) and that we lacked information on comorbidities.…”

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12

“…[2][3][4][5][6] Earlier reports of individuals with the same or similar microdeletions have emphasized that these individuals do not have cognitive impairment or a neurological phenotype. 6 However, three of the patients with deletions in 17q12 in our cohort had features of neurological involvement: two patients had speech delay and one patient had moderate-to-severe mental retardation.…”

“…Deletions of 17q12, including the HNF1b (hepatocyte nuclear factor 1-beta also known as transcription factor 2, MIM 189907) gene, are associated with maturity onset diabetes of the young type 5 (MODY5), as well as with cystic renal disease, renal dilations, pancreatic atrophy, and liver abnormalities. [2][3][4][5][6] Earlier reports of this contiguous gene deletion syndrome involving HNF1b have suggested that cognitive impairment is not part of the phenotype conveyed by these deletions. Mefford et al 6 have reported that recurrent deletions in this region spanning 1.8 Mb are one of the few examples of contiguous gene deletion syndromes that present without mental retardation.…”

Spectrum of HNF1B Mutations in a Large Cohort of Patients Who Harbor Renal Diseases

“…Mutations that were not deletions of the entire gene are shown in Table 2. One patient was carrying a de novo heterozygous deletion of exon 4, which was previously reported (3,13). Twenty-four different heterozygous small mutations (11 missense, five nonsense, five frameshift, and three splice site mutations) were found in 32 probands.…”