NPHP1 gene-associated nephronophthisis is associated with an occult retinopathy

Birtel, Johannes; Spital, Georg; Book, Marius; Habbig, Sandra; Bäumner, Sören; Riehmer, Vera; Beck, Bodo B.; Rosenkranz, David; Bolz, Hanno J.; Dahmer-Heath, Mareike; Herrmann, Philipp; König, Jens; Issa, Peter Charbel

doi:10.1016/j.kint.2021.06.012

Cited by 7 publications

(6 citation statements)

References 57 publications

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“…These cases did not have occult retinopathy on fundus autofluorescence imaging. One individual had an additional CEP290 variant and presented with more severe retinal degeneration 57 …”

Section: Discussionmentioning

confidence: 99%

“…One individual had an additional CEP290 variant and presented with more severe retinal degeneration. 57 Stokman et al reported biallelic mutations in NPHP1 in 12 patients with NPHP, two patients with Joubert NPHP1 encodes the nephrocystin-1 protein at the base of cilia in cells of the kidney, respiratory tract, and retina. This protein is not well understood but is thought to be important for cell division and cell signaling.…”

Section: Discussionmentioning

confidence: 99%

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NPHP1‐Related ciliopathies: A new case and major review of the ophthalmic manifestations of 147 reported cases

Reddy,

Simmers,

Shah

et al. 2023

Clinical Case Reports

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“…These cases did not have occult retinopathy on fundus autofluorescence imaging. One individual had an additional CEP290 variant and presented with more severe retinal degeneration 57 …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

NPHP1‐Related ciliopathies: A new case and major review of the ophthalmic manifestations of 147 reported cases

Reddy,

Simmers,

Shah

et al. 2023

Clinical Case Reports

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“…NPHP1 is the most common gene involved leading usually to ESKD within the first two decades of life. Extra-renal manifestations of NPHP1 are shared with many other ciliopathies, such as cerebellar malformations, nystagmus, and intellectual disability (typical of Joubert's syndrome), retinal degeneration (typical of Senior-Løken syndrome or Cogan's syndrome), and impairment of the liver [4,5].…”

Section: Discussionmentioning

confidence: 99%

“…NPHP1 may lead to end-stage kidney disease (ESKD) in 5-10% of cases during childhood or adolescence [2]. NPHP1 frequently presents as an isolated renal phenotype, but also extra-renal manifestations are described such as progressive retinal dystrophy (Senior-Løken syndrome) [3,4], neurological abnormalities leading to cerebellar ocular-renal syndrome (Joubert syndrome), and liver fibrosis [5,6].…”

mentioning

confidence: 99%

Co-Occurrence of Nephronophthisis Type 1 and Alström Syndrome: A Case Report

Rossoni

Lugani

Orsi

et al. 2023

Nephron

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We describe the unique case of a patient in whom two ciliopathies with autosomal recessive transmission were clinically and molecularly diagnosed: Nephronophthisis type1 (NPHP1) and Alström Syndrome (AS). NPHP1 is one of the main genetic causes of terminal kidney failure in childhood. AS is an ultra-rare multi-systemic disease, characterized by progressive kidney disease, hepatic failure, dystrophy of the rods and cones to blindness, slowly progressive neuro-sensory deafness, dilated cardiomyopathy, obesity, insulin resistance / type 2 diabetes mellitus. The coexistence in the same patient of two rare syndromes with overlapping clinical manifestations but genetically different is an eventuality to be considered. This case report would describe the onset and progression of the multi-organ manifestations of both syndromes to highlight that ciliopathies present a strong phenotype overlap but also specific peculiarities. Therefore, to make a correct diagnosis, that is essential to achieve the best clinical management, could be challenging.

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“…In addition to nephronophthisis, 15% of patients have retinal dystrophy (Senior–Løken syndrome) or neurological (Joubert syndrome) phenotypes 16 . The retinal phenotype may be mild 17 . Joubert syndrome (JS) is characterised by cerebellar ataxia, mental retardation, hypotonia, and neonatal respiratory dysregulation 18 .…”

Section: Introductionmentioning

confidence: 99%

A genotype-to-phenotype approach suggests under-reporting of single nucleotide variants in nephrocystin-1 (NPHP1) related disease (UK 100,000 Genomes Project)

Leggatt¹,

Cheng²,

Narain³

et al. 2023

Sci Rep

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Autosomal recessive whole gene deletions of nephrocystin-1 (NPHP1) result in abnormal structure and function of the primary cilia. These deletions can result in a tubulointerstitial kidney disease known as nephronophthisis and retinal (Senior–Løken syndrome) and neurological (Joubert syndrome) diseases. Nephronophthisis is a common cause of end-stage kidney disease (ESKD) in children and up to 1% of adult onset ESKD. Single nucleotide variants (SNVs) and small insertions and deletions (Indels) have been less well characterised. We used a gene pathogenicity scoring system (GenePy) and a genotype-to-phenotype approach on individuals recruited to the UK Genomics England (GEL) 100,000 Genomes Project (100kGP) (n = 78,050). This approach identified all participants with NPHP1-related diseases reported by NHS Genomics Medical Centres and an additional eight participants. Extreme NPHP1 gene scores, often underpinned by clear recessive inheritance, were observed in patients from diverse recruitment categories, including cancer, suggesting the possibility of a more widespread disease than previously appreciated. In total, ten participants had homozygous CNV deletions with eight homozygous or compound heterozygous with SNVs. Our data also reveals strong in-silico evidence that approximately 44% of NPHP1 related disease may be due to SNVs with AlphaFold structural modelling evidence for a significant impact on protein structure. This study suggests historical under-reporting of SNVS in NPHP1 related diseases compared with CNVs.

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NPHP1 gene-associated nephronophthisis is associated with an occult retinopathy

Cited by 7 publications

References 57 publications

NPHP1‐Related ciliopathies: A new case and major review of the ophthalmic manifestations of 147 reported cases

NPHP1‐Related ciliopathies: A new case and major review of the ophthalmic manifestations of 147 reported cases

Co-Occurrence of Nephronophthisis Type 1 and Alström Syndrome: A Case Report

A genotype-to-phenotype approach suggests under-reporting of single nucleotide variants in nephrocystin-1 (NPHP1) related disease (UK 100,000 Genomes Project)

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