scholarly journals Molecular Genetic Diagnosis of Omani Patients With Inherited Cystic Kidney Disease

2019 ◽  
Vol 4 (12) ◽  
pp. 1751-1759 ◽  
Author(s):  
Intisar Al Alawi ◽  
Issa Al Salmi ◽  
Fatma Al Rahbi ◽  
Mohamed Al Riyami ◽  
Naifain Al Kalbani ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Molecular Genetic Diagnosis

Autosomal dominant tubule-interstitial kidney disease, including medullary cystic disease

2018 ◽  
Author(s):  
John A. Sayer
Keyword(s):  
Kidney Disease ◽  
Autosomal Dominant ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Molecular Genetic Diagnosis ◽  
End Stage

The term medullary cystic kidney disease (MCKD) describes a group of autosomal dominantly inherited renal disorders. The term MCKD is used interchangeably with other terms, most commonly autosomal dominant interstitial kidney disease, and now may be distinguished using a molecular genetic diagnosis into at least three types. These include MCKD type 1, MCKD type 2 (also known now as uromodulin-associated kidney disease), and REN-associated kidney disease. Each of these types have phenotypic overlap but with a few distinguishing features. MCKD typically leads to end-stage renal failure between 30 and 70 years of age. Extrarenal features may include gout and childhood anaemia.

Nephronophthisis and medullary cystic kidney disease

2018 ◽  
Author(s):  
John A. Sayer
Keyword(s):  
Renal Failure ◽  
Kidney Disease ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Autosomal Recessive Disorder ◽  
Later Life ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Medullary Cystic Kidney Disease ◽  
Precise Diagnosis

The inherited cystic kidney conditions nephronophthisis (NPHP) and medullary cystic kidney disease (MCKD) have previously been referred to as a NPHP–MCKD complex. This descriptive term was based on histological studies where the renal pathological features were common to both disorders. Both conditions may also present with insidious renal impairment and a urine concentrating defect, but they are genetically distinct. NPHP is an autosomal recessive disorder leading to established renal failure usually within the first three decades of life, and it is a ciliopathy. In contrast, MCKD is an autosomal dominantly inherited disorder leading to renal failure in later life, typically between 30 and 60 years of age. A molecular genetic diagnosis is helpful for both disorders, allowing a more precise diagnosis, screening of at risk relatives and avoiding the need for renal biopsy. Treatment of both conditions remains supportive.

scholarly journals Preimplantation Genetic Testing for Kidney Disease-Related Genes: A Laboratory’s Experience

2021 ◽  
Vol 52 (8) ◽  
pp. 684-690
Author(s):  
Jessica L. Chaperon ◽  
Nina M. Wemmer ◽  
Trudy A. McKanna ◽  
Dinah M. Clark ◽  
Maggie A. Westemeyer ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Clinical Indication ◽  
Common Disease ◽  
Reference Laboratory ◽  
Preimplantation Genetic Testing ◽  
Kidney Involvement ◽  
Molecular Genetic Diagnosis

<b><i>Introduction:</i></b> Recent literature highlights the clinical utility of genetic testing for patients with kidney disease. Genetic testing provides significant benefits for reproductive risk counseling, including the option of in vitro fertilization with preimplantation genetic testing for monogenic disease (PGT-M). PGT-M allows for a significant reduction in risk for a pregnancy affected with the familial disease. We aim to summarize our experience with PGT-M for genes with kidney involvement as either a primary or secondary feature of the disease. <b><i>Methods:</i></b> All PGT-M tests performed by the reference laboratory between September 2010 and July 2020 were reviewed for clinical indication and cases for which the disease tested included a renal component. Each patient referred for PGT-M had an existing molecular genetic diagnosis themselves or in their family. Frequency of each condition, gene, inheritance pattern, and year over year increase in referral cases was analyzed. <b><i>Results:</i></b> In the study cohort, the most common disease targeted was autosomal dominant polycystic kidney disease, caused by pathogenic variants in the <i>PKD1</i> or <i>PKD2</i> genes, which accounted for 16.5% (64/389) of cases. The 5 most common referral indications accounted for 51.9% (202/389) of the cases. Autosomal recessive inheritance accounted for 52.0% (26/50) of conditions for which PGT-M was performed. The number of PGT-M tests performed for conditions that included either primary or secondary kidney disease increased from 5 cases in 2010 to 47 cases in the 2020 study period. <b><i>Discussion/Conclusion:</i></b> These data suggest that the pursuit of PGT-M by couples at risk for passing on conditions with a kidney component is common and has significantly increased since 2010. With this rising trend of patients undergoing PGT-M and the prerequisite of molecular genetic confirmation in the PGT-M process, this study underscores the importance of the reproductive component to a molecular genetic diagnosis for patients with kidney disease, especially as the accessibility of genetic testing and utilization by nephrologists grows.

scholarly journals Clinical utility of genetic testing in the precision management of pediatric patients with kidney disease

Kidney360 ◽  
2020 ◽  
pp. 10.34067/KID.0002272020
Author(s):  
Nasim Bekheirnia ◽  
Kevin E. Glinton ◽  
Linda Rossetti ◽  
Joshua Manor ◽  
Wuyan Chen ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Clinical Laboratory ◽  
Diagnostic Yield ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Chromosomal Microarray ◽  
Wide Range

Background: As genetic testing increasingly integrates into the practice of nephrology, our understanding of the basis of many kidney disorders has exponentially increased. Given this, we recently initiated a Renal Genetics Clinic (RGC) at our large, urban children's hospital for patients with kidney disorders. Methods: Genetic testing was performed in Clinical Laboratory Improvement Amendments (CLIA) certified laboratories using single gene testing, multi-gene panels, chromosomal microarray (CMA), or exome sequencing (ES). Results: A total of 192 patients were evaluated in this clinic, with cystic kidney disease (49/192) being the most common reason for referral followed by Congenital Anomalies of the Kidney and Urinary Tract (CAKUT: 41/192) and hematuria (38/192). Genetic testing was performed for 158 patients with an overall diagnostic yield of 81/158 (51.3%). In the patients who reached a genetic diagnosis, 16/81 (19.7%), medical or surgical treatment of the patients were impacted, and in 12/81 (14.8%), previous clinical diagnoses were changed to more accurate genetic diagnoses. Conclusions: Such testing provided an accurate diagnosis for children and in some cases led to further diagnosis in seemingly asymptomatic family members and changes to overall medical management. Genetic testing, as facilitated by such a specialized clinical setting, thus appears to have clear utility in the diagnosis and counseling of patients with a wide range of kidney manifestations.

Phthalate Esters, Cystic Kidney Disease in Animals and Possible Effects on Human Health: A Review

1990 ◽  
Vol 9 (6) ◽  
pp. 397-401 ◽  
Author(s):  
K.N. Woodward
Keyword(s):  
Kidney Disease ◽  
Human Health ◽  
Phthalate Esters ◽  
Renal Cysts ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Peroxisome Proliferation ◽  
Peroxisome Proliferators ◽  
Prolonged Administration ◽  
Route Of Exposure

1 Phthalate esters are known to cause hepatic peroxisome proliferation in rodents and, after prolonged administration, hepatocarcinogenesis. Peroxisome proliferators as a group are hepatocarcinogenic. The mechanism is not known but it does not appear to involve a direct genotoxic element. 2 DEHP and DBP have been shown to cause renal cysts in rodents and they also produce renal peroxisome proliferation. There are no data to causally link the two phenomena. 3 Although renal cysts have been noted in haemodialysis patients and haemodialysis is a route of exposure to DEHP, there are no data to suggest a cause and effect relationship. 4 More studies are needed on the mechanism of renal cystogenesis.

Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism

2020 ◽  
Vol 33 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Tatsushi Tanaka ◽  
Kohei Aoyama ◽  
Atsushi Suzuki ◽  
Shinji Saitoh ◽  
Haruo Mizuno
Keyword(s):  
Congenital Hypothyroidism ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Japanese Patients ◽  
Thyroid Stimulating Hormone ◽  
Allelic Variant ◽  
Genetic Investigation ◽  
Pathogenic Variants ◽  
Recessive Genes ◽  
Molecular Genetic Diagnosis

AbstractObjectivesCongenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations.MethodsWe enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH.ResultsWe identified potentially pathogenic bi-allelic variants in DUOX2, TSHR, and TPO in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in NKX2-1 (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (DUOX2, TSHR, TG, DUOXA2, and TPO) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic DUOX2 variants showed a more severe clinical presentation in infancy than those with bi-allelic TSHR variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic DUOX2 variants.ConclusionsThe prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.

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