Skeletal impairment in Pierson syndrome: Is there a role for lamininβ2 in bone physiology?

Autor: Edith Bonnelye, Bruno Ranchin, Irma Machuca-Gayet, Justine Bacchetta, Martin Zenker, Delphine Farlay, Camille Beaufils, Caroline Freychet, Alice Fassier, Aurélia Bertholet-Thomas
Přispěvatelé: Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institute of Human Genetics, University Hospital Magdeburg, Université Grenoble Alpes - UFR Médecine - Département de Maïeutique (UGA UFRMDM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de référence des maladies rénales rares Néphrogones [CHU-HCL, Lyon], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Néphrologie Rhumatologie Dermatologie, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Est-Centre de référence Maladies Rénales Rares, École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université Grenoble Alpes (UGA), HCL Groupement Hospitalier Est-Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de référence Maladies Rénales Rares
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
medicine.medical_specialty
Histology
Nephrotic Syndrome
Adolescent
Physiology
Endocrinology
Diabetes and Metabolism
030232 urology & nephrology
Renal function
Scoliosis
03 medical and health sciences
0302 clinical medicine
Laminin
Pupil Disorders
Internal medicine
Medicine
Humans
Abnormalities
Multiple
Eye Abnormalities
Congenital nephrotic syndrome
ComputingMilieux_MISCELLANEOUS
Myasthenic Syndromes
Congenital
Kidney
[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics
biology
business.industry
Neuromuscular Diseases
Microcoria
medicine.disease
Tacrolimus
Transplantation
030104 developmental biology
medicine.anatomical_structure
Endocrinology
[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
Mutation
biology.protein
Female
business
Zdroj: BONE
BONE, 2018, 106, pp.187-193. ⟨10.1016/j.bone.2017.10.015⟩
BONE, Elsevier, 2018, 106, pp.187-193. ⟨10.1016/j.bone.2017.10.015⟩
ISSN: 8756-3282
DOI: 10.1016/j.bone.2017.10.015⟩
Popis: Introduction Pierson syndrome is caused by a mutation of LAMB2, encoding for laminin β2. Clinical phenotype is variable but usually associates congenital nephrotic syndrome (CNS) and ocular abnormalities. Neuromuscular impairment has also been described. Methods We report on a 15-year old girl, suffering from Pierson Syndrome, who developed severe bone deformations during puberty. This patient initially displayed CNS and microcoria, leading to the clinical diagnosis of Pierson syndrome. Genetic analysis revealed a truncating mutation and a splice site mutation of LAMB2. The patient received a renal transplantation (R-Tx) at the age of 3. After R-Tx, renal evolution was simple, the patient receiving low-dose corticosteroids, tacrolimus and mycophenolate mofetil. At the age of 12, bone deformations progressively appeared. At the time of bone impairment, renal function was subnormal (glomerular filtration rate using iohexol clearance 50 mL/min per 1.73 m2), and parameters of calcium/phosphate metabolism were normal (calcium 2.45 mmol/L, phosphorus 1.30 mmol/L, PTH 81 ng/L, ALP 334 U/L, 25OH-D 73 nmol/L). Radiographs showed major deformations such as scoliosis, genu varum and diffuse epiphyseal abnormalities. A high resolution scanner (HR-pQCT) was performed, demonstrating a bone of “normal low” quantity and quality; major radial and cubital deformations were observed. Stainings of laminin β2 were performed on bone and renal samples from the patient and healthy controls: as expected, laminin β2 was expressed in the control kidney but not in the patient's renal tissue, and a similar pattern was observed in bone. Conclusion This is the first case of skeletal impairment ever described in Pierson syndrome. Integrin α3β1, receptor for laminin β2, are found in podocytes and osteoblasts, and the observation of both the presence of laminin β2 staining in healthy bone and its absence in the patient's bone raises the question of a potential role of laminin β2 in bone physiology.
Databáze: OpenAIRE
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