Neurodevelopmental deficits in Pierson (microcoria-congenital nephrosis) syndrome
| Autor: | Verena Matejas, Pierre Cochat, Thomas Aigner, Elke Wühl, Olaf Wendler, André Reis, Rene G. VanDeVoorde, Jillene Kogan, Martin Zenker, Aleksandra Zurowska, Raymonde Bouvier, Iga Lesniewska, Joachim Weis |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Pathology Nephrotic Syndrome Neuromuscular disease Molecular Sequence Data Severe muscular hypotonia Blindness Internal medicine Genetics medicine Humans Abnormalities Multiple Eye Abnormalities Muscle Skeletal Congenital nephrotic syndrome Genetics (clinical) Base Sequence Psychomotor retardation business.industry Genetic disorder Infant Syndrome Microcoria medicine.disease Endocrinology Child Preschool Mutation Muscle Hypotonia Female Laminin Psychomotor Disorders medicine.symptom Psychomotor disorder business Nephrotic syndrome |
| Zdroj: | American Journal of Medical Genetics Part A. :311-319 |
| ISSN: | 1552-4833 1552-4825 |
| DOI: | 10.1002/ajmg.a.31564 |
| Popis: | Pierson syndrome is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct eye abnormalities with microcoria reported as the most prominent clinical feature. LAMB2 mutations leading to lack of laminin beta2 were identified as the molecular cause underlying Pierson syndrome. Although LAMB2 is known to be expressed in the neuromuscular system, and defects of the neuromuscular junctions had been found in laminin beta2-deficient mice, no consistent neurological phenotype has been described clinically in murine or human laminin beta2-deficiency before. This is likely due to the early lethality from renal failure. Here we provide a detailed description of neurological manifestations and development in four patients affected by Pierson syndrome, who survived until the age of 1.3-4.8 years owing to renal replacement therapy. Severe muscular hypotonia, psychomotor retardation, and blindness were present in three patients harboring truncating mutations on both LAMB2 alleles. These symptoms were not attributable to complications of chronic renal failure, thus representing a primary feature of the genetic disorder. Alterations in skeletal muscle tissue from one case were compatible with a chronic denervating process. One affected girl, however, exhibited a milder course of renal disease, normal development, and preserved vision, presumably owing to some residual LAMB2 function. Our findings indicate that severe neurodevelopmental deficits have to be considered as part of Pierson syndrome, at least in the presence of biallelic functional null mutations (complete lack of laminin beta2). This is an important issue in the counseling of parents of an affected newborn or infant. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text