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.
Bone. 2018 Jan;106:187-193. doi: 10.1016/j.bone.2017.10.015. Epub 2017 Oct 16.
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.
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 1.73m), 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.
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.
皮尔逊综合征是由编码层粘连蛋白β2 的 LAMB2 基因突变引起的。临床表现多样，但通常与先天性肾病综合征（CNS）和眼部异常有关。也有神经肌肉损伤的描述。
我们报告了一例 15 岁女孩，患有皮尔逊综合征，在青春期时出现严重的骨骼畸形。该患者最初表现为 CNS 和小瞳孔，导致临床诊断为皮尔逊综合征。基因分析显示 LAMB2 存在截断突变和剪接位点突变。患者在 3 岁时接受了肾移植（R-Tx）。R-Tx 后，肾功能正常，患者接受低剂量皮质类固醇、他克莫司和霉酚酸酯治疗。12 岁时，骨骼畸形逐渐出现。在骨损伤时，肾功能异常（使用 iohexol 清除率的肾小球滤过率为 50mL/min/1.73m），钙/磷代谢参数正常（钙 2.45mmol/L，磷 1.30mmol/L，PTH 81ng/L，碱性磷酸酶 334U/L，25-羟维生素 D 73nmol/L）。影像学显示严重畸形，如脊柱侧凸、膝内翻和弥漫性骨骺异常。进行了高分辨率扫描（HR-pQCT），显示“正常低值”的骨量和质量；观察到主要的桡骨和尺骨畸形。对患者和健康对照者的骨和肾组织进行了层粘连蛋白β2 的染色：正如预期的那样，层粘连蛋白β2 在对照肾脏中表达，但在患者的肾脏组织中不表达，在骨骼中也观察到类似的模式。
这是皮尔逊综合征中首次描述的骨骼损伤病例。整合素 α3β1 是层粘连蛋白β2 的受体，存在于足细胞和成骨细胞中，在健康骨骼中观察到层粘连蛋白β2 的染色存在，而在患者的骨骼中观察到其缺失，这提出了层粘连蛋白β2 在骨骼生理学中可能具有潜在作用的问题。
