ABSTRACT
PURPOSE: To describe the ophthalmological characteristics in a group of Noonan syndrome patients with proven mutations in the PTPN11 gene. METHODS: Thirty-five Noonan syndrome patients with PTPN11 gene mutations underwent ophthalmological exams, which consisted of external inspection, slit-lamp biomicroscopy examination and an ophthalmoscopic examination after instillation of 1.0% tropicamide or 1.0% cyclopentolate. RESULTS: All 35 patients had at least one abnormality upon ophthalmological examination. The eyelid and external eye abnormalities were the prevailing features, followed by prominent corneal nerves on slit-lamp exam. Fundus changes were detected in 8% of the subjects, mainly associated with high myopia. No statistically significant differences were observed among the patients presenting specific mutations in the PTPN11 gene. CONCLUSIONS: The current study further supports the finding that ocular symptoms account for a large fraction of the clinical manifestations of NS. Additional characteristics are described here. The roles for the various mutations of PTPN11 in ocular development are yet to be established.
Subject(s)
Eye Abnormalities/diagnosis , Noonan Syndrome/diagnosis , Adolescent , Adult , Child , Child, Preschool , Eye Abnormalities/genetics , Female , Genotype , Humans , Infant , Male , Mutation , Noonan Syndrome/genetics , Phenotype , Protein Tyrosine Phosphatase, Non-Receptor Type 11/geneticsABSTRACT
Silver-Russell syndrome (SRS) is characterized by severe intrauterine and postnatal growth retardation in association with a typical small triangular face and other variable features. Genetic and epigenetic disturbances are detected in about 50% of the patients. Most frequently, SRS is caused by altered gene expression on chromosome 11p15 due to hypomethylation of the telomeric imprinting center (ICR1) that is present in at least 40% of the patients. Maternally inherited duplications encompassing ICR1 and ICR2 domains at 11p15 were found in a few patients, and a microduplication restricted to ICR2 was described in a single SRS child. We report on a microduplication of the ICR2 domain encompassing the KCNQ1, KCNQ1OT1, and CDKN1C genes in a three-generation family: there were four instances of paternal transmissions of the microduplication from a single male uniformly resulting in normal offspring, and five maternal transmissions, via two clinically normal sisters, with all the children exhibiting SRS. This report provides confirmatory evidence that a microduplication restricted to the ICR2 domain results in SRS when maternally transmitted.
Subject(s)
Chromosomes, Human, Pair 11/genetics , Gene Duplication/genetics , Silver-Russell Syndrome/genetics , Silver-Russell Syndrome/pathology , Telomere/genetics , Child , Child, Preschool , Comparative Genomic Hybridization , Cyclin-Dependent Kinase Inhibitor p57/genetics , DNA Copy Number Variations/genetics , DNA Methylation/genetics , Female , Humans , KCNQ1 Potassium Channel/genetics , Male , Pedigree , Potassium Channels, Voltage-Gated/genetics , Protein Structure, Tertiary/geneticsABSTRACT
Objetivo: Analisar os achados clínicos e radiológicos da displasia cleidocraniana. Método: A Unidade de Genética do ICr-HCFMUSP, em conjunto com o setor da Radiologia, estudou 12 pacientes pertencentes a 8 famílias com displasia cleidocraniana...
Objectives: To analyse the clinical and radiological finding of cleidocranial dysplasia. Methods: The Genetics Unit of ICr-HCFMUSP, along with the Radiology department, performed the study of 12 patients from eight families of cleidocranial dysplasia...