RESUMO
BACKGROUND/AIMS: Osteoporosis-pseudoglioma (OPPG) syndrome is a rare disorder characterized by congenital or infancy-onset visual loss and severe juvenile osteoporosis. OPPG is caused by homozygous mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. We present three novel homozygous LRP5 mutations found in 3 unrelated Turkish children with consanguineous parents, along with clinical phenotypes and response to treatment with bisphosphonates (bisP). METHODS/RESULTS: The LRP5 gene was analyzed by direct sequencing after PCR amplification. Mutation screening for LRP5 revealed homozygous nonsense R1002X mutation in the first patient and homozygous missense mutations V336M and G507S in the second and third patient, respectively. The parents were heterozygous for these mutations. The patients' eye symptoms began during the first months of life but the OPPG diagnoses were made based on skeletal deformities and osteopenia after 4 years of age. The patients' bone mineral density Z scores were very low and consistent with osteopenia. All patients were treated with bisP for 3.5-7 years. CONCLUSION: We report three novel LRP5 mutations in 3 Turkish patients with OPPG. We show that the response of bisP therapy has improved the lumbar spinal bone mineral density Z scores and the patients' quality of life as the bone pains decreased.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Resistência a Medicamentos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Mutação , Osteogênese Imperfeita/tratamento farmacológico , Osteogênese Imperfeita/genética , Substituição de Aminoácidos , Densidade Óssea/efeitos dos fármacos , Criança , Pré-Escolar , Códon sem Sentido , Consanguinidade , Oftalmopatias/tratamento farmacológico , Oftalmopatias/genética , Feminino , Heterozigoto , Humanos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Masculino , Mutação de Sentido Incorreto , Osteogênese Imperfeita/metabolismo , Osteogênese Imperfeita/fisiopatologia , Medição da Dor/efeitos dos fármacos , TurquiaRESUMO
Tunisian Androctonus species, for long time discussed, were recognized on the basis of mitochondrial 16S rDNA sequences. Although the analysed nucleotide sequence is rather short (about 300 bp), the obtained phlogenetic trees revealed that A. amoreuxi and A. aeneas form two well-supported sister clades against A. australis haplotypes. Each specimen of the very rare species A. aeneas showed a specific haplotype, but together formed a well-defined clade. Some A. amoreuxi specimens highlighted unidirectional mitochondrial introgression from neighbouring A. australis population. Within A. australis, previously described, subspecies subdivision (A. a .hector and A. a. garzonii) was not supported.
