GANAB and PKD1 Variations in a 12 Years Old Female Patient With Early Onset of Autosomal Dominant Polycystic Kidney Disease

Waldrop, Elizabeth; Al‐Obaide, Mohammed A. I.; Vasylyeva, Tetyana L.

doi:10.3389/fgene.2019.00044

Cited by 12 publications

(9 citation statements)

References 27 publications

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“…Patients with early ADPKD are more likely to have such biallelic transmission than those with classical ADPKD [36,41]. Digenic disease with variants in PKD1 and the newly identified ADPKD gene GANAB has also recently been identified in a child with early ADPKD [43]. Severe ADPKD may also be caused by combined transmission of mutations in PKD1 or 2 and other cystic kidney disease genes such as HNF1B or PKHD1 [42], but it is unclear to what proportion of ADPKD VEO children this applies.…”

Section: Extrarenal Disease Manifestations and Distinguishing Phenocomentioning

confidence: 99%

The wind of change in the management of autosomal dominant polycystic kidney disease in childhood

2021

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Significant progress has been made in understanding the genetic basis of autosomal dominant polycystic kidney disease (ADPKD), quantifying disease manifestations in children, exploring very-early onset ADPKD as well as pharmacological delay of disease progression in adults. At least 20% of children with ADPKD have relevant, yet mainly asymptomatic disease manifestations such as hypertension or proteinuria (in line with findings in adults with ADPKD, where hypertension and cardiovascular damage precede decline in kidney function). We propose an algorithm for work-up and management based on current recommendations that integrates the need to screen regularly for hypertension and proteinuria in offspring of affected parents with different options regarding diagnostic testing, which need to be discussed with the family with regard to ethical and practical aspects. Indications and scope of genetic testing are discussed. Pharmacological management includes renin-angiotensin system blockade as first-line therapy for hypertension and proteinuria. The vasopressin receptor antagonist tolvaptan is licensed for delaying disease progression in adults with ADPKD who are likely to experience kidney failure. A clinical trial in children is currently ongoing; however, valid prediction models to identify children likely to suffer kidney failure are lacking. Non-pharmacological interventions in this population also deserve further study.

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Section: Extrarenal Disease Manifestations and Distinguishing Phenocomentioning

confidence: 99%

The wind of change in the management of autosomal dominant polycystic kidney disease in childhood

2021

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“…Group 1: Congenital Disorders of Glycosylation Primarily Affecting the Liver (Table 1) GANAB-CDG (OMIM #600666) due to deficiency of the catalytic alpha subunit of Glucosidase Alpha Neutral AB affects twenty-one patients described worldwide, with polycystic kidney and polycystic liver disease (13,14). MPI-CDG (CDG-Ib, OMIM #602579).…”

Section: Resultsmentioning

confidence: 99%

Liver Involvement in Congenital Disorders of Glycosylation: A Systematic Review

Colantuono

D’Acunto

Melis

et al. 2021

Journal of Pediatric Gastroenterology &Amp; Nutrition

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An ever-increasing number of disturbances in glycosylation have been described to underlie certain unexplained liver diseases presenting either almost isolated or in a multi-organ context. We aimed to update previous literature screenings which had identified up to 23 forms of congenital disorders of glycosylation (CDG) with associated liver disease. We conducted a comprehensive literature search of three scientific electronic databases looking at articles published during the last 20 years (January 2000-October 2020). Eligible studies were case reports/series reporting liver involvement in CDG patients. Our systematic review led us to point out 41 forms of CDG where the liver is primarily affected (n ¼ 7) or variably involved in a multisystem disease with mandatory neurological abnormalities (n ¼ 34). Herein we summarize individual clinical and laboratory presentation characteristics of these 41 CDG and outline their main presentation and diagnostic cornerstones with the aid of two synoptic tables. Dietary supplementation strategies have hitherto been investigated only in seven of these CDG types with liver disease, with a wide range of results. In conclusion, the systematic review recognized a liver involvement in a somewhat larger number of CDG variants corresponding to about 30% of the total of CDG so far reported, and it is likely that the number may increase further. This information could assist in an earlier correct diagnosis and a possibly proper management of these disorders.

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“…Early onset cystic kidney disease in individuals with variants in PKD1 and another ADPKD‐causing gene has been reported before. A case of a girl with pathogenic variants in both PKD1 and GANAB has been reported with onset at age 12 years, which is an earlier presentation than is typical (Harris & Torres, 2002; Waldrop et al., 2019). There have been some cases of double heterozygous individuals with ADPKD who have variants in both PKD1 and PKD2 (Harris & Torres, 2002).…”

Section: Discussionmentioning

confidence: 99%

Molecular genetic diagnosis of kidney ciliopathies: Lessons from interpreting genomic sequencing data and the requirement for accurate phenotypic data

Orr,

Olinger,

Iosifidou

et al. 2023

Annals of Human Genetics

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Introduction: Massively parallel sequencing (MPS) techniques have made a major impact on the identification of the genetic basis of inherited kidney diseases such as the ciliopathy autosomal dominant polycystic kidney disease (ADPKD). Great care must be taken when analysing MPS data in isolation from accurate phenotypic information, as this can cause misdiagnosis. Methods: Here, we describe a family trio, recruited to the Genomics England 100,000 Genomes Project, labelled as having cystic kidney disease, who were genetically unsolved following routine data analysis pipelines. We performed a bespoke reanalysis of Whole Genome Sequencing (WGS) data and coupled this with revised phenotypic data and targeted PCR and Sanger sequencing to provide a precise molecular genetic diagnosis. Results: We detected a heterozygous PKD1 frameshift variant within the WGS data which segregated with the redefined ADPKD phenotypes. An additional heterozygous exon deletion in ALG8 was also found in affected and unaffected individuals, but its precise clinical significance remains unclear. Conclusion: This case illustrates that reanalysis of WGS data in unsolved cases of cystic kidney disease is valuable. Clinical phenotypes must be reassessed as these may have been incorrectly recorded and evolve over time. Undertaking additional studies including genotype‐phenotype correlation in wider family members provides useful diagnostic information.

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GANAB and PKD1 Variations in a 12 Years Old Female Patient With Early Onset of Autosomal Dominant Polycystic Kidney Disease

Cited by 12 publications

References 27 publications

The wind of change in the management of autosomal dominant polycystic kidney disease in childhood

The wind of change in the management of autosomal dominant polycystic kidney disease in childhood

Liver Involvement in Congenital Disorders of Glycosylation: A Systematic Review

Molecular genetic diagnosis of kidney ciliopathies: Lessons from interpreting genomic sequencing data and the requirement for accurate phenotypic data

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