Polykystose rénale autosomique dominante : le traitement est-il pour demain ?

Gall, Emilie Cornec-Le; Meur, Yann Le

doi:10.1016/j.nephro.2014.03.003

Cited by 2 publications

(3 citation statements)

References 64 publications

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“…The high rate of kidney cysts observed in BBS patients is in favor of this hypothesis (7 out of 11 in our series, in accordance with the literature ( 16) ). We hypothesize that cyst formation in the male genital tract of BBS patients results from a physio-pathological mechanism similar to that described in polycystic kidney disease: cyst formation would result from a dysfunction of the dimer polycystin 1–polycystin 2 (PC1-PC2) ( 11 , 41 , 42 ), inducing excess cell growth, proliferation, and secretion. In accordance with a recent discussion about the role of BBS proteins in the cystogenesis ( 43 ), we presume that, in ciliated epididymal cells like in kidney cells, BBSome interacts with PC1 to stabilize the complex ( Fig.…”

Section: Discussionmentioning

confidence: 90%

“…A high concentration of cytoplasmic Ca2+ represses adenylate cyclase VI (AC VI). The AC VI produces cAMP stimulating AMPk pathway and PKA pathway which are resulting in a stimulation of cell proliferation and CFTR-linked chloride secretion respectively ( 42 ). BBSome of the primary cilia stabilizes the PC1 complex and allows a functional dimerization with PC2 ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

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Reproduction Function in Male Patients With Bardet Biedl Syndrome

Koscinski

Mark

Messaddeq

et al. 2020

The Journal of Clinical Endocrinology &Amp; Metabolism

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Purpose Bardet-Biedl syndrome (BBS) is a ciliopathy with a wide spectrum of symptoms due to primary cilia dysfunction including genitourinary developmental anomalies as well as impaired reproduction particularly in males. Primary cilia are known to be required at the following steps of reproduction function: (1) genitourinary organogenesis, (2) in the fetal firing of hypothalamo-pituitary axe, (3) sperm flagellum structure and (4) the first zygotic mitosis conducted by proximal sperm centriole. BBS phenotype is not fully understood. Methods This study explored all steps of reproduction in 11 French male patients with identified BBS mutations. Results BBS patients presented frequently genitourinary malformations as cryptorchidism (5/11), short scrotum (5/8), micropenis (5/8) but unexpectedly, normal testis size (7/8). Ultrasonography highlighted epididymal cysts or agenesis of one seminal vesicle in some cases. Sexual hormones levels were normal in all patients except one. Sperm numeration was normal in 8 out of the 10 obtained samples. Five to 45% of sperm presented a progressive motility. Electronic microscopy did not reveal any homogeneous abnormality. Moreover, a psychological approach pointed a decreased self-confidence linked to blindness and obesity explaining why so few BBS patients express a child wish. Conclusions PC dysfunction in BBS impacts embryology of the male genital tract, especially epididymis, penis and scrotum through an insufficient fetal androgen production. However, in adults, sperm structure does not seem to be impacted. These results should be confirmed in a greater BBS patient cohort, focusing on fertility.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Reproduction Function in Male Patients With Bardet Biedl Syndrome

Koscinski

Mark

Messaddeq

et al. 2020

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…21,22 In this context, accurate description of the ADPKD phenotype is important and represents a key step to delineate which patients should receive these new treatments. Since the discovery of both genes about 20 years ago, several studies have reported the ADPKD phenotypic spectrum, but only a few studies have focused on the population with PKD2 mutations.…”

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confidence: 99%

PKD2 -Related Autosomal Dominant Polycystic Kidney Disease: Prevalence, Clinical Presentation, Mutation Spectrum, and Prognosis

Gall

Audrézet

Renaudineau

et al. 2017

American Journal of Kidney Diseases

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Background PKD2-related autosomal dominant polycystic kidney disease (ADPKD) is widely acknowledged to be of milder severity than PKD1-related disease, but population-based studies depicting the exact burden of the disease are lacking. We aimed to revisit PKD2 prevalence, clinical presentation, mutation spectrum, and prognosis through the Genkyst cohort. Study Design Case series, January 2010 to March 2016. Settings & Participants Genkyst study participants are individuals older than 18 years from 22 nephrology centers from western France with a diagnosis of ADPKD based on Pei criteria or at least 10 bilateral kidney cysts in the absence of a familial history. Publicly available whole-exome sequencing data from the ExAC database were used to provide an estimate of the genetic prevalence of the disease. Outcomes Molecular analysis of PKD1 and PKD2 genes. Renal survival, age- and sex-adjusted estimated glomerular filtration rate. Results The Genkyst cohort included 293 patients with PKD2 mutations (203 pedigrees). PKD2 patients with a nephrology follow-up corresponded to 0.63 (95% CI, 0.54–0.72)/10,000 in Brittany, while PKD2 genetic prevalence was calculated at 1.64 (95% CI, 1.10–3.51)/10,000 inhabitants in the European population. Median age at diagnosis was 42 years. Flank pain was reported in 38.9%; macroscopic hematuria, in 31.1%; and cyst infections, in 15.3% of patients. At age 60 years, the cumulative probability of end-stage renal disease (ESRD) was 9.8% (95% CI, 5.2%–14.4%), whereas the probability of hypertension was 75.2% (95% CI, 68.5%–81.9%). Although there was no sex influence on renal survival, men had lower kidney function than women. Nontruncating mutations (n = 36) were associated with higher age-adjusted estimated glomerular filtration rates. Among the 18 patients with more severe outcomes (ESRD before age 60), 44% had associated conditions or nephropathies likely to account for the early progression to ESRD. Limitations Younger patients and patients presenting with milder forms of PKD2-related disease may not be diagnosed or referred to nephrology centers. Conclusions Patients with PKD2-related ADPKD typically present with mild disease. In case of accelerated degradation of kidney function, a concomitant nephropathy should be ruled out.

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Polykystose rénale autosomique dominante : le traitement est-il pour demain ?

Cited by 2 publications

References 64 publications

Reproduction Function in Male Patients With Bardet Biedl Syndrome

Reproduction Function in Male Patients With Bardet Biedl Syndrome

PKD2 -Related Autosomal Dominant Polycystic Kidney Disease: Prevalence, Clinical Presentation, Mutation Spectrum, and Prognosis

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