Massively Enlarged Polycystic Kidneys in Monozygotic Twins With TCF2/HNF-1β (Hepatocyte Nuclear Factor-1β) Heterozygous Whole-Gene Deletion

Faguer, Stanislas; Bouissou, F; Dumazer, P.; Guitard, Joëlle; Bellanné‐Chantelot, Christine; Chauveau, Dominique

doi:10.1053/j.ajkd.2007.06.016

Cited by 24 publications

(13 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12

et al. 2009

View full text Add to dashboard Cite

Deletions in chromosome 17q12 encompassing the HNF1b gene cause cystic renal disease and maturity onset diabetes of the young, and have been recently described as the first recurrent genomic deletion leading to diabetes. Earlier reports of patients with this microdeletion syndrome have suggested an absence of cognitive impairment, differentiating it from most other contiguous gene deletion syndromes. The reciprocal duplication of 17q12 is rare and has been hypothesized to be associated with an increased risk of epilepsy and mental retardation. We conducted a detailed clinical and molecular characterization of four patients with a deletion and five patients with a reciprocal duplication of this region. Our patients with deletion of 17q12 presented with cognitive impairment, cystic renal disease, seizures, and structural abnormalities of the brain. Patients with reciprocal duplications manifest with cognitive impairment and behavioral abnormalities, but not with seizures. Our findings expand the phenotypic spectrum associated with rearrangements of 17q12 and show that cognitive impairment is a part of the phenotype of individuals with deletions of 17q12.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Only one report of monozygotic twins with MODY5 has been published. Although detailed phenotypes of the patients were not described, the severity in renal and pancreatic defects appeared to be similar between the twins. The current report is thus unique in that the severity of renal and pancreatic dysfunction of the twins markedly differed.…”

Section: Discussionmentioning

confidence: 58%

Phenotypic differences and similarities of monozygotic twins with maturity‐onset diabetes of the young type 5

Ohara

Okada

Yamada

et al. 2019

J of Diabetes Invest

View full text Add to dashboard Cite

Here, we report phenotypic differences and similarities of monozygotic twins with maturity‐onset diabetes of the young type 5 harboring a partial deletion of chromosome 17q12. The proband and her twin sister manifested complete aplasia and marked hypoplasia, respectively, of the body and tail of the pancreas. Whereas both twins showed marked hypoplasia of the right kidney and multiple cysts in both kidneys, only the proband's sister showed hydronephrosis in the left kidney. The proband had profound defects in insulin and glucagon secretion, as well as mild renal dysfunction, whereas her sister had pronounced renal dysfunction accompanied by mild defects in insulin and glucagon secretion. Both twins manifested hypomagnesemia and hyperuricemia, but no apparent liver dysfunction or intellectual disability. The severity of renal and pancreatic defects differed between monozygotic twins with maturity‐onset diabetes of the young type 5, suggesting that the phenotypes of this condition are determined not solely by genetic factors.

show abstract

“…In adults, mutations of HNF1B may be associated with low serum magnesium or low serum potassium level due to renal loss of either ion [5,30]. These peculiar findings have not been reported so far in animal models, which hampers molecular analysis.…”

Section: Discussionmentioning

confidence: 99%

“…It mostly encompasses (1) bilateral renal hypodysplasia most often translating into hyperechogenic kidneys or renal cortical cysts from the antenatal period through childhood; (2) in adulthood, renal cysts are frequently lacking or few, and (3) at any age, the nephropathy harbors a profile of chronic tubulointerstitial nephritis with slowly progressive renal decline, low-range proteinuria without hematuria, and a distinctive renal loss of magnesium and potassium [1,5,6]. In addition, we and others have emphasized a wide inter- and intra-family variability [5,7]. Beside whole-gene deletions, which account for more than half of all mutations [8], private heterozygous point mutations of HNF1B have been reported, including missense, nonsense, frameshift and splicing mutations [7].…”

Section: Introductionmentioning

confidence: 99%

Expression of Renal Cystic Genes in Patients with <i>HNF1B </i>Mutations

et al. 2012

Self Cite

View full text Add to dashboard Cite

Background/Aims: HNF1B nephropathy is characterized by dominantly inherited renal hypodysplasia with few cysts, slow renal decline and hypomagnesemia. Mice with antenatal inactivation of HNF1B are characterized by polycystic kidneys, renal failure and a profound decrease in cystic gene (Pkhd1, Umod, Pkd2) expression. Mice with inactivation after postnatal day 10 have no renal phenotype. Methods: Quantification of mRNA expression of HNF1B, six of its potential target genes (PKHD1, PKD1, PKD2, IFT88, TMEM27 and UMOD) and three genes involved in the Mg²⁺ renal homeostasis (ATP1A1, FXYD2 and CLDN16) in the urinary sediment of 11 individuals with mutation of HNF1B and in 9 controls (non-invasive assessment of the renal transcriptome). Results: As compared to controls, no difference was observed in the urinary mRNA amount of HNF1B and the renal cystic genes. A significant increase in the expression of ATP1A1, which encodes the α1-subunit of the Na⁺/K⁺-ATPase, was identified in HNF1B patients consistent with its role in Mg²⁺ homeostasis. Conclusion:Assessment of mRNA expression in urinary sediment is a non-invasive method applicable to gain insights into the pathophysiology of inherited nephropathies in humans. HNF1B nephropathy is generally not associated with postnatal down-expression of renal cystic genes in human, a finding consistent with mouse models.

show abstract

Massively Enlarged Polycystic Kidneys in Monozygotic Twins With TCF2/HNF-1β (Hepatocyte Nuclear Factor-1β) Heterozygous Whole-Gene Deletion

Cited by 24 publications

References 14 publications

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12

Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12

Phenotypic differences and similarities of monozygotic twins with maturity‐onset diabetes of the young type 5

Expression of Renal Cystic Genes in Patients with <i>HNF1B </i>Mutations

Contact Info

Product

Resources

About