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Matrix Biology : Journal of the... Oct 2018The glomerular basement membrane (GBM) is an important component of the kidney's glomerular filtration barrier. Like all basement membranes, the GBM contains type IV... (Review)
Review
The glomerular basement membrane (GBM) is an important component of the kidney's glomerular filtration barrier. Like all basement membranes, the GBM contains type IV collagen, laminin, nidogen, and heparan sulfate proteoglycan. It is flanked by the podocytes and glomerular endothelial cells that both synthesize it and adhere to it. Mutations that affect the GBM's collagen α3α4α5(IV) components cause Alport syndrome (kidney disease with variable ear and eye defects) and its variants, including thin basement membrane nephropathy. Mutations in LAMB2 that impact the synthesis or function of laminin α5β2γ1 (LM-521) cause Pierson syndrome (congenital nephrotic syndrome with eye and neurological defects) and its less severe variants, including isolated congenital nephrotic syndrome. The very different types of kidney diseases that result from mutations in collagen IV vs. laminin are likely due to very different pathogenic mechanisms. A better understanding of these mechanisms should lead to targeted therapeutic approaches that can help people with these rare but important diseases.
Topics: Abnormalities, Multiple; Collagen Type IV; Eye Abnormalities; Glomerular Basement Membrane; Humans; Laminin; Mutation; Myasthenic Syndromes, Congenital; Nephritis, Hereditary; Nephrotic Syndrome; Pupil Disorders
PubMed: 29673759
DOI: 10.1016/j.matbio.2018.04.008 -
Archives de Pediatrie : Organe Officiel... Nov 2011
Topics: Abnormalities, Multiple; Eponyms; Eye Abnormalities; Humans; Molecular Diagnostic Techniques; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Pupil Disorders
PubMed: 21903364
DOI: 10.1016/j.arcped.2011.08.002 -
American Journal of Kidney Diseases :... Apr 2018
Review
Topics: Abnormalities, Multiple; Diagnosis, Differential; Eye Abnormalities; Humans; Kidney; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Periodicals as Topic; Pupil Disorders
PubMed: 29579420
DOI: 10.1053/j.ajkd.2018.02.001 -
Ophthalmic Genetics Oct 2023Pierson syndrome and X-linked Alport syndrome result from pathogenic variants in and , respectively, and both affect basement membranes in the kidney and the eye. This... (Review)
Review
BACKGROUND
Pierson syndrome and X-linked Alport syndrome result from pathogenic variants in and , respectively, and both affect basement membranes in the kidney and the eye. This study describes the ocular features in an individual with a homozygous pathogenic variant and compares the reported abnormalities in Pierson syndrome with those in Alport syndrome.
METHODS
A 28-year-old man who developed kidney failure 10 years previously and subsequently had an atrial septal defect repair was suspected of having genetic kidney disease on the basis of his likely diagnosis of Focal and Segmental Glomerulosclerosis (FSGS), his young age at presentation, and his cardiac anomaly. He then underwent Whole Exome Sequencing and a formal ophthalmological examination.
RESULTS
The patient was found to have a homozygous Likely Pathogenic missense variant (p.(Arg1719Cys)) in consistent with the diagnosis of Pierson syndrome. He had normal visual acuity, normal optic globe and cornea size, and normal lens appearance on direct examination. Upon further testing, his cornea demonstrated central thinning. There was also increased corneal endothelial pleomorphism, a reduced foveal reflex, and a blunted foveal curvature, similar to the features seen in X-linked Alport syndrome.
CONCLUSION
Our patient had a later onset form of Pierson syndrome or "FSGS type 5, with or without ocular abnormalities," consistent with his "milder" missense variant. The resemblance of the ocular features in Pierson syndrome and X-linked Alport syndrome suggests that mutations in and have similar effects on basement membranes and the pathogenesis of ocular damage.
Topics: Male; Humans; Adult; Nephritis, Hereditary; Glomerulosclerosis, Focal Segmental; Nephrotic Syndrome; Mutation; Collagen Type IV
PubMed: 37537573
DOI: 10.1080/13816810.2023.2240881 -
Nature Reviews. Nephrology Feb 2021The glomerular basement membrane (GBM) is a key component of the glomerular capillary wall and is essential for kidney filtration. The major components of the GBM... (Review)
Review
The glomerular basement membrane (GBM) is a key component of the glomerular capillary wall and is essential for kidney filtration. The major components of the GBM include laminins, type IV collagen, nidogens and heparan sulfate proteoglycans. In addition, the GBM harbours a number of other structural and regulatory components and provides a reservoir for growth factors. New technologies have improved our ability to study the composition and assembly of basement membranes. We now know that the GBM is a complex macromolecular structure that undergoes key transitions during glomerular development. Defects in GBM components are associated with a range of hereditary human diseases such as Alport syndrome, which is caused by defects in the genes COL4A3, COL4A4 and COL4A5, and Pierson syndrome, which is caused by variants in LAMB2. In addition, the GBM is affected by acquired autoimmune disorders and metabolic diseases such as diabetes mellitus. Current treatments for diseases associated with GBM involvement aim to reduce intraglomerular pressure and to treat the underlying cause where possible. As our understanding about the maintenance and turnover of the GBM improves, therapies to replace GBM components or to stimulate GBM repair could translate into new therapies for patients with GBM-associated disease.
Topics: Anti-Glomerular Basement Membrane Disease; Diabetic Nephropathies; Glomerular Basement Membrane; Humans; Myasthenic Syndromes, Congenital; Nephritis, Hereditary; Nephrotic Syndrome; Pupil Disorders
PubMed: 32839582
DOI: 10.1038/s41581-020-0329-y -
Sultan Qaboos University Medical Journal Nov 2020Pierson syndrome is caused by mutations in the gene causing absent β2 laminin, which is a normal component of the basement membranes of the mature glomerulus,...
Pierson syndrome is caused by mutations in the gene causing absent β2 laminin, which is a normal component of the basement membranes of the mature glomerulus, structures in the anterior eye and neuromuscular junctions. The mutations manifest as congenital nephrotic syndrome and microcoria which are characteristic ocular features of this disease. These mutations may also result in neurological abnormalities such as hypotonia and psychomotor retardation. We report a two-month old boy who presented to the Pediatrics Department of Dr. Ruth K. M. Pfau Civil Hospital, Karachi, Pakistan, in 2015, with the typical features of microcoria and congenital nephrotic syndrome. The hypocalcaemia, hypoproteinaemia and probable immunocompromised state consequent to nephrotic syndrome resulted in seizures, hypothyroidism and urosepsis. Despite being treated aggressively with high dose antibiotics, ionotropic support, angiotensin-converting enzyme inhibitors, thyroxine replacement and nutritional support, the infant died due to significant multiorgan disease including renal failure and septic shock.
Topics: Child; Humans; Hypothyroidism; Infant; Male; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Pupil Disorders; Shock, Septic
PubMed: 33414946
DOI: 10.18295/squmj.2020.20.04.017 -
CEN Case Reports Dec 2023Pierson syndrome (PS) is a rare autosomal recessive disease, characterized by congenital nephrotic syndrome (CNS), and ocular and neurologic abnormalities. In affected...
Pierson syndrome (PS) is a rare autosomal recessive disease, characterized by congenital nephrotic syndrome (CNS), and ocular and neurologic abnormalities. In affected cases, there is abnormal b-2 laminin which is compound of the several basement membranes caused by inherited mutations in the LAMB2 gene. Although patients have mutations in the same gene, the phenotype is highly variable. In this case series, the relationship between genotype and phenotype is emphasized, and information about the clinical follow-up of the patients is presented. Hereby, we report four pediatric cases with PS as a result of mutation in the LAMB2 gene. Clinical spectrum of LAMB2-associated disorders varies from mild-to-severe ocular, kidney, and neurologic involvement. Since genotype-phenotype correlation in PS has not been clearly demonstrated, we recommend that all patients with ophthalmic anomalies and glomerular proteinuria should be tested for LAMB2 mutations.
PubMed: 38038886
DOI: 10.1007/s13730-023-00838-y -
Ophthalmic Surgery, Lasers & Imaging... Nov 2020Pierson syndrome is a rare genetic disease defined by congenital nephrotic syndrome in association with microcoria. The authors aim to describe the posterior segment and...
BACKGROUND AND OBJECTIVE
Pierson syndrome is a rare genetic disease defined by congenital nephrotic syndrome in association with microcoria. The authors aim to describe the posterior segment and retinal features in Pierson syndrome.
PATIENTS AND METHODS
A retrospective chart review of nine patients diagnosed with Pierson syndrome was ascertained. Details of ophthalmic history, ocular examination, retinal imaging, and surgical interventions were obtained during a median duration of 17 months of follow-up (range: 6 to 60 months). Retinal interventions included scatter laser photocoagulation and surgical retinal repair.
RESULTS
Sixteen eyes of nine patients were included. The axial length of five eyes with flat retina was 26.59 mm ± 0.99 mm. Highly myopic features including tessellated fundus with accompanying optic disc pallor, unidentifiable cup, and abnormal retinal vascular emanation from the disc were observed in all eyes (100%), whereas 12 eyes (75%) had parapapillary chorioretinal atrophy. Features of abnormal retinal vascularization included avascular peripheral retina on fluorescein angiography, aberrant course of the temporal arcades in 13 eyes (81.3%), and straightened nasal retinal blood vessels in 12 eyes (75%). Tortuous retinal blood vessels were observed in three eyes (18.75%). Surgical repair was performed in five out of seven eyes with rhegmatogenous retinal detachment (RRD). Recurrence was observed in all eyes, which required two to three procedures to achieve final reattachment.
CONCLUSIONS
Combined features of high axial myopia with incomplete peripheral vascular maturation characterize the posterior segment in Pierson syndrome. Careful posterior segment examination is essential to detect RRD or retinal neovascularization. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:618-627.].
Topics: Child; Humans; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Pupil Disorders; Retinal Detachment; Retrospective Studies; Visual Acuity
PubMed: 33231694
DOI: 10.3928/23258160-20201104-03 -
BMC Ophthalmology Feb 2023Pierson syndrome is a rare autosomal recessive disorder that causes congenital nephrotic syndrome, neurodevelopmental abnormalities, and several ocular signs. The...
BACKGROUND
Pierson syndrome is a rare autosomal recessive disorder that causes congenital nephrotic syndrome, neurodevelopmental abnormalities, and several ocular signs. The Pierson syndrome is caused by a mutation of the LAMB2 gene, that encodes laminin beta 2, which is expressed in the glomerular basement membrane, in neuromuscular junctions, and within ocular structures. First described by Pierson et al., the ocular signs of Pierson syndrome include microcoria, which is most characteristic sign, as well as iris abnormalities, cataract, glaucoma, and retinal detachment.
CASE PRESENTATION
Herein, we report the case of a young female who, at 16 months, was diagnosed with congenital nephrotic syndrome, subsequently underwent a kidney transplant at age 4,did cataract surgery with IOL implantation in both eyes at age of 2 years and presented with ocular signs including high myopia, band keratopathy, t, nystagmus, retina, and optic nerve atrophy, she did not show nor did the family report any neurodevelopmental abnormalities. her genetic studies this missense variant c.970T< C p. (Cys324Arg) of LAMB2, later she developed spontaneous hyphema along with vitreous haemorrhage and increased intra ocular pressure in her left eye, she underwent cyclophotocouagulation to treat her high IOP.
CONCLUSION
LAMB 2 mutations can be associated with multiple ocular signs that varies from mild to severe form, we are her to report our case who did not present with the typical ocular sign of microcoria for PS, did not have any neurodevelopmental abnormality and presented with hyphaemia 2ndry to iris neovascularisation with vitreous haemorrhage with neovascular glaucoma.
Topics: Female; Humans; Nephrotic Syndrome; Hyphema; Glaucoma, Neovascular; Vitreous Hemorrhage; Hemorrhage; Cataract
PubMed: 36829142
DOI: 10.1186/s12886-023-02826-3 -
Archivos Argentinos de Pediatria Jun 2020Pierson syndrome is characterized by congenital nephrotic syndrome and bilateral microcoria. Genetically, mutations in the LAMB2 gene, which encodes the laminin β2...
Pierson syndrome is characterized by congenital nephrotic syndrome and bilateral microcoria. Genetically, mutations in the LAMB2 gene, which encodes the laminin β2 chain, lead to this disorder. To date, 98 cases and 50 different mutations have been reported in literature. There are no specific therapies for Pierson syndrome and treatment is supportive. The prognosis is poor because of progressive impairment of renal function and complications of renal failure. We report a novel homozygous mutation (c.1890G>T, p.Q630H) in the LAMB2 gene in a patient with Pierson syndrome who had atypical phenotypic feature such as epidermolysis bullosa.
Topics: Female; Genetic Markers; Homozygote; Humans; Infant; Laminin; Mutation; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Phenotype; Pupil Disorders
PubMed: 32470267
DOI: 10.5546/aap.2020.eng.e288