Camille Beaufils1, Delphine Farlay2, Irma Machuca-Gayet2, Alice Fassier3, Martin Zenker4, Caroline Freychet5, Edith Bonnelye2, Aurélia Bertholet-Thomas5, Bruno Ranchin5, Justine Bacchetta6. 1. Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices, Civils de Lyon, 69677 Bron, France. Electronic address: Camille.beaufils@chu-lyon.fr. 2. INSERM, UMR 1033, Université Claude Bernard Lyon 1, Lyon, France. 3. Service de Chirurgie Orthopédique Pédiatrique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France. 4. Institute of Human Genetics, University Hospital Magdeburg, Germany. 5. Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices, Civils de Lyon, 69677 Bron, France. 6. Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices, Civils de Lyon, 69677 Bron, France; INSERM, UMR 1033, Université Claude Bernard Lyon 1, Lyon, France; Service de Chirurgie Orthopédique Pédiatrique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France; Institute of Human Genetics, University Hospital Magdeburg, Germany; Faculté de Médecine Lyon Est, Université de Lyon, France, Lyon. Electronic address: justine.bacchetta@chu-lyon.fr.
Abstract
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 50mL/min per 1.73m2), and parameters of calcium/phosphate metabolism were normal (calcium 2.45mmol/L, phosphorus 1.30mmol/L, PTH 81ng/L, ALP 334U/L, 25OH-D 73nmol/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.
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 50mL/min per 1.73m2), and parameters of calcium/phosphate metabolism were normal (calcium 2.45mmol/L, phosphorus 1.30mmol/L, PTH 81ng/L, ALP 334U/L, 25OH-D 73nmol/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.