RESUMO
Point mutation and loss of heterozygosity (LOH) analyses were performed in 12 Polish patients with a classic symptom of NF2 - bilateral vestibular schwannomas (BVS). In 5 patients (41.7%), germline mutations were found in the NF2 gene: 2 previously reported substitutions (c.592C>T and c.52C>T) and 3 novel mutations (c.1001_1002insG, c.1029_1030insCC, c.774_778dupGAATG). In addition, LOH analysis of 30 tumour samples from 10 patients revealed a molecular basis of NF2 in 3 patients (25%) that did not have any germline mutation. The molecular defects in sporadic cases of NF2 are still being discussed.
Assuntos
Mutação em Linhagem Germinativa/genética , Perda de Heterozigosidade , Neurofibromatose 2/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Neurofibromatose 2/diagnóstico , Neurofibromatose 2/epidemiologia , Polônia/epidemiologia , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita SimplesRESUMO
Noonan syndrome (NS) belongs to one of the most frequent genetic disorders with autosomal dominant pattern of inheritance. The main symptoms of NS are short stature, congenital heart defects, thorax deformities and specific dysmorphic features: hypertelorism, low set ears. short and wide neck, wide spaced nipples. The clinical picture ofNS changes with the age, which impedes the proper diagnosis in adults. We present two familial cases of Noonan syndrome with mutated PTPN11 gene in probands and one of their parents and siblings. We analyzed clinical features with regards to NS diagnostic criteria.
Assuntos
Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Adulto , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , LinhagemRESUMO
Noonan syndrome (NS; MIM 163950) is an autosomal dominant disorder. With incidence of 1/1000 to 1/2500 live births, NS belongs to the most common genetic disorders. Typical features of NS are: short stature, chest deformities, congenital heart defects, cryptorchidism and dysmorphic features. Mutations of PTPN11 gene (located on chromosome 12q24.1) are responsible for NS and are identified in 33-60% cases. Less than half of the cases are familial. This paper presents current opinion on clinical symptoms, molecular pathogenesis and possibilities of growth hormone therapy. The genotype--phenotype correlation is also discussed.