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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 -
BMC Medical Genetics Apr 2020Pierson syndrome (PS) is a rare autosomal recessive disorder, characterized by congenital nephrotic syndrome and microcoria. Advances in renal replacement therapies have...
BACKGROUND
Pierson syndrome (PS) is a rare autosomal recessive disorder, characterized by congenital nephrotic syndrome and microcoria. Advances in renal replacement therapies have extended the lifespan of patients, whereas the full clinical spectrum of PS in infancy and beyond remains elusive.
CASE PRESENTATION
We present the case of a 12-month-old boy with PS, manifesting as the bilateral microcoria and congenital nephrotic syndrome. He was born without asphyxia, and was neurologically intact from birth through the neonatal period. Generalized muscle weakness and hypotonia were recognized from 3 months of age. The infant showed recurrent vomiting at age 5 months of age, and was diagnosed with gastroesophageal reflux and intestinal malrotation. Despite the successful surgical treatment, vomiting persisted and led to severely impaired growth. Tulobuterol treatment was effective in reducing the frequency of vomiting. Targeted sequencing confirmed that he had a compound heterozygous mutation in LAMB2 (NM_002292.3: p.Arg550X and p.Glu1507X). A search of the relevant literature identified 19 patients with severe neuro-muscular phenotypes. Among these, only 8 survived the first 12 months of life, and one had feeding difficulty with similar gastrointestinal problems.
CONCLUSIONS
This report demonstrated that severe neurological deficits and gastrointestinal dysfunction may emerge in PS patients after the first few months of life.
Topics: Abnormalities, Multiple; Gastrointestinal Tract; Humans; Infant; Laminin; Male; Mutation; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Phenotype; Pupil Disorders
PubMed: 32295525
DOI: 10.1186/s12881-020-01019-9 -
Nephron 2021Pierson syndrome (PIERSS) is a rare autosomal recessive disorder characterized by the combination of congenital nephrotic syndrome (CNS) and extrarenal symptoms...
Pierson syndrome (PIERSS) is a rare autosomal recessive disorder characterized by the combination of congenital nephrotic syndrome (CNS) and extrarenal symptoms including ocular malformations and neurodevelopmental deficits. PIERSS is caused by biallelic pathogenic variants in the LAMB2 gene leading to the defects of β2-laminin, the protein mainly expressed in the glomerular basement membrane, ocular structures, and neuromuscular junctions. Severe complications of PIERSS lead to the fatal outcome in early childhood in majority of the cases. We report a case of 5-year-old girl with severe phenotype of PIERSS caused by biallelic functional null variants of the LAMB2 gene. Due to consequences of CNS, the patient required bilateral nephrectomy and peritoneal dialysis since early infancy. The course was additionally complicated by tubulopathy, life-threatening infections, severe hypertension, erythropoietin-resistant anemia, generalized muscular hypotonia, neurogenic bladder, profound neurodevelopmental delay, epilepsy, gastrointestinal problems, secondary hypothyroidism, and necessity of repeated ocular surgery due to microcoria, cataract, and nystagmus. Due to multidisciplinary efforts, at the age of 4 years, the kidney transplantation was possible. Currently, the renal graft has an excellent function; however, the girl presents severe neurodevelopmental delay. The report presents a unique long-term follow-up of severe PIERSS with a few new phenotypical findings. It highlights the clinical problems and challenges in management of this rare condition.
Topics: Child, Preschool; Female; Follow-Up Studies; Humans; Kidney Transplantation; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Phenotype; Pupil Disorders; Severity of Illness Index
PubMed: 34058744
DOI: 10.1159/000516247 -
Kidney International Reports Sep 2023Laminin subunit beta-2 -associated disease, termed Pierson syndrome, presents with congenital nephrotic syndrome, ocular symptoms, and neuromuscular symptoms. In recent...
INTRODUCTION
Laminin subunit beta-2 -associated disease, termed Pierson syndrome, presents with congenital nephrotic syndrome, ocular symptoms, and neuromuscular symptoms. In recent years, however, the widespread use of next-generation sequencing (NGS) has helped to discover a variety of phenotypes associated with this disease. Therefore, we conducted this systematic review.
METHODS
A literature search of patients with variants was conducted, and 110 patients were investigated, including 12 of our patients. For genotype-phenotype correlation analyses, the extracted data were investigated for pathogenic variant types, the severity of nephropathy, and extrarenal symptoms. Survival analyses were also performed for the onset age of end-stage kidney disease (ESKD).
RESULTS
Among all patients, 81 (78%) presented with congenital nephrotic syndrome, and 52 (55%) developed ESKD within 12 months. The median age at ESKD onset was 6.0 months. Kidney survival analysis showed that patients with biallelic truncating variants had a significantly earlier progression to ESKD than those with other variants (median age 1.2 months vs. 60.0 months, < 0.05). Although the laminin N-terminal domain is functionally important in laminin proteins, and variants in the laminin N-terminal domain are said to result in a severe kidney phenotype such as earlier onset age and worse prognosis, there were no significant differences in onset age of nephropathy and progression to ESKD between patients with nontruncating variants located in the laminin N-terminal domain and those with variants located outside this domain.
CONCLUSION
This study revealed a diversity of -associated diseases, characteristics of nephropathy, and genotype-phenotype correlations.
PubMed: 37705905
DOI: 10.1016/j.ekir.2023.06.019 -
Kidney International Reports Dec 2020
PubMed: 33305134
DOI: 10.1016/j.ekir.2020.09.023 -
Ophthalmic Genetics Jun 2021: To report a patient with Pierson syndrome who presented with neovascular glaucoma (NVG) after cataract surgery.: Retrospective case report.: A 17-year old monocular...
: To report a patient with Pierson syndrome who presented with neovascular glaucoma (NVG) after cataract surgery.: Retrospective case report.: A 17-year old monocular female presented with sudden onset of pain and decreased vision in the right eye. On examination, she had intraocular pressure (IOP) of 50 mmHg, aggressive iris neovascularization (NVI) and 3-piece IOL. Fundus examination revealed pale disc with tessellated fundus and parapapillary atrophy. Vascular arcades were vertically stretched with avascular ischemic retina starting from the near periphery. Macula appeared thin and atrophic. An intravitreal injection of 0.05 mg/0.1 ml bevacizumab was given to the right eye followed by Ahmed glaucoma valve (AGV) implantation. Assessment of her brother revealed similar posterior segment changes. A subsequent urine analysis showed proteinuria and high albumin to creatinine ratio. Next-generation sequencing for gene revealed a homozygous c.4573 + 1 G > A variant confirming the diagnosis of Pierson syndrome.: This case expands our knowledge on retinal ischemia in the setting of Pierson syndrome. Close monitoring after intraocular surgery is recommended to look for the development of NVG.
Topics: Adolescent; Angiogenesis Inhibitors; Bevacizumab; Combined Modality Therapy; Female; Glaucoma Drainage Implants; Glaucoma, Neovascular; High-Throughput Nucleotide Sequencing; Humans; Intraocular Pressure; Laminin; Lens Implantation, Intraocular; Male; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Phacoemulsification; Pupil Disorders; Retrospective Studies; Siblings; Tonometry, Ocular; Young Adult
PubMed: 33554690
DOI: 10.1080/13816810.2021.1881982 -
BMC Nephrology Aug 2020Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) cause substantial morbidity and mortality. In Japan, there is a lack of knowledge regarding... (Observational Study)
Observational Study
BACKGROUND
Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) cause substantial morbidity and mortality. In Japan, there is a lack of knowledge regarding the characteristics of CNS and INS. This study aimed to clarify the characteristics of CNS and INS in Japan.
METHODS
This cross-sectional nationwide survey obtained data from 44 institutions in Japan managing 92 patients with CNS or INS, by means of two survey questionnaires sent by postal mail. Patients aged < 16 years by 1 April 2015, with a diagnosis of CNS or INS, were included in this study. The primary outcome was end-stage kidney disease.
RESULTS
A total of 83 patients with CNS or INS were analyzed. The most frequent disease type was non-Finnish (60.2%); 33 patients (39.8%) had Finnish type. Among those with non-Finnish-type disease, 26 had no syndrome and 24 had a syndrome, of which the most frequent was Denys-Drash syndrome (70.8%). Patients with non-Finnish-type disease with syndrome showed the earliest progression to end-stage kidney disease compared with the other two groups, whereas patients with non-Finnish-type disease without syndrome progressed more slowly compared with the other two groups. In the Finnish-type group, the disease was diagnosed the earliest; a large placenta was reported more frequently; genetic testing was more frequently performed (93.8%); mental retardation was the most frequent extra-renal symptom (21.2%); and thrombosis and infection were more frequent compared with the other groups. Patients with non-Finnish-type disease with syndrome had a higher frequency of positive extra-renal symptoms (79.2%), the most common being urogenital symptoms (54.2%). Treatment with steroids and immunosuppressants was more frequent among patients with non-Finnish-type disease without syndrome. Two patients with non-Finnish-type disease without syndrome achieved complete remission. In all groups, unilateral nephrectomy was performed more often than bilateral nephrectomy and peritoneal dialysis was the most common renal replacement therapy.
CONCLUSIONS
The present epidemiological survey sheds light on the characteristics of children with CNS and INS in Japan. A high proportion of patients underwent genetic examination, and patient management was in accord with current treatment recommendations and practices.
TRIAL REGISTRATION
Not applicable.
Topics: Adolescent; Child; Child, Preschool; Denys-Drash Syndrome; Disease Progression; Female; Genetic Testing; Glucocorticoids; Humans; Immunosuppressive Agents; Infant; Infant, Newborn; Intellectual Disability; Japan; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Myasthenic Syndromes, Congenital; Nephrectomy; Nephrotic Syndrome; Organ Size; Placenta; Pregnancy; Pupil Disorders; Renal Replacement Therapy; Surveys and Questionnaires; Syndrome
PubMed: 32838745
DOI: 10.1186/s12882-020-02010-5 -
PloS One 2022Records of anthropogenic marine debris and the threats it poses are increasing worldwide, yet we know relatively little about the distribution of benthic debris. The...
Records of anthropogenic marine debris and the threats it poses are increasing worldwide, yet we know relatively little about the distribution of benthic debris. The seafloor is the final destination for a large proportion of debris due to the degradation and sinking of items. A more detailed understanding of debris distributions in hotspots such as urbanised estuaries can help decision makers target management and remediation activities. We selected sites frequented by fishers and boaters in Sydney Harbour, an urbanised estuary, to investigate the impacts of recreational activities on debris abundance. The aim of this study was to examine variation in macro debris (>5mm in diameter) type and abundance at two habitat types (piers and non-piers). We chose five locations at various distances from the estuary mouth. In each location SCUBA teams performed fixed transects at two sites, one under a pier and one over nearby soft-sediment habitat. Debris was recovered by the divers and brought to the surface for classification and disposal. Surveys were repeated multiple times at each location between November 2019 and February 2020, recording a total of 2803 debris items over 36 survey events. Overall, piers had more than ten times the debris abundance of soft-sediment sites, and much higher proportion of debris types related to recreational fishing. Over half of the debris items in this study were plastic (65%), and approximately 70% of the total debris was classified as related to recreational fishing. This trait was most prominent in debris at sites closest to the estuary mouth, likely reflecting increased fishing activity in this area. This study indicates that policy makers and community groups in urbanised estuaries should focus monitoring, reduction, and remediation efforts near artificial structures such as piers, and that public awareness campaigns should target the behaviour of recreational users of these structures.
Topics: Estuaries; Plastics; Ecosystem; Environmental Monitoring; Waste Products
PubMed: 36576908
DOI: 10.1371/journal.pone.0274512 -
Journal of Human Genetics Apr 2020Null variants in LAMB2 cause Pierson syndrome (PS), a severe congenital nephrotic syndrome with ocular and neurological defects. Patients' kidney specimens show complete...
Null variants in LAMB2 cause Pierson syndrome (PS), a severe congenital nephrotic syndrome with ocular and neurological defects. Patients' kidney specimens show complete negativity for laminin β2 expression on glomerular basement membrane (GBM). In contrast, missense variants outside the laminin N-terminal (LN) domain in LAMB2 lead to milder phenotypes. However, we experienced cases not showing these typical genotype-phenotype correlations. In this paper, we report six PS patients: four with mild phenotypes and two with severe phenotypes. We conducted molecular studies including protein expression and transcript analyses. The results revealed that three of the four cases with milder phenotypes had missense variants located outside the LN domain and one of the two severe PS cases had a homozygous missense variant located in the LN domain; these variant positions could explain their phenotypes. However, one mild case possessed a splicing site variant (c.3797 + 5G>A) that should be associated with a severe phenotype. Upon transcript analysis, this variant generated some differently sized transcripts, including completely normal transcript, which could have conferred the milder phenotype. In one severe case, we detected the single-nucleotide substitution of c.4616G>A located outside the LN domain, which should be associated with a milder phenotype. However, we detected aberrant splicing caused by the creation of a novel splice site by this single-base substitution. These are novel mechanisms leading to an atypical genotype-phenotype correlation. In addition, all four cases with milder phenotypes showed laminin β2 expression on GBM. We identified novel mechanisms leading to atypical genotype-phenotype correlation in PS.
Topics: Amino Acid Substitution; Child; Child, Preschool; Female; Glomerular Basement Membrane; Humans; Infant; Laminin; Male; Mutation, Missense; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Protein Domains; Pupil Disorders; RNA Splicing
PubMed: 31959872
DOI: 10.1038/s10038-019-0715-0 -
Nature Communications Jan 2023Laminin polymerization is the major step in basement membranes assembly. Its failures cause laminin N-terminal domain lamininopathies including Pierson syndrome. We have...
Laminin polymerization is the major step in basement membranes assembly. Its failures cause laminin N-terminal domain lamininopathies including Pierson syndrome. We have employed cryo-electron microscopy to determine a 3.7 Å structure of the trimeric laminin polymer node containing α1, β1 and γ1 subunits. The structure reveals the molecular basis of calcium-dependent formation of laminin lattice, and provides insights into polymerization defects manifesting in human disease.
Topics: Humans; Laminin; Cryoelectron Microscopy; Polymerization; Nephrotic Syndrome; Pupil Disorders; Basement Membrane
PubMed: 36658135
DOI: 10.1038/s41467-023-36077-z