RESUMO
BACKGROUND: Genetic variants involving the MED13L gene can lead to an autosomal dominant syndrome characterised by intellectual disability/developmental delay and facial dysmorphism. METHODS: We investigated two cases (one familial and one isolated) of intellectual disability with speech delay and dysmorphic facial features by whole-exome sequencing analyses. Further, we performed a literature review about clinical and molecular aspects of MED13L gene and syndrome. RESULTS: Two MED13L variants have been identified [MED13L(NM_015335.5):c.4417C>T and MED13L(NM_015335.5):c.2318delC] and were classified as pathogenic according to the ACMG (American College of Medical Genetics and Genomics) guidelines. One of the variants was present in sibs. CONCLUSIONS: The two pathogenic variants identified have not been previously reported. Importantly, this is the first report of a familial case of MED13L nonsense mutation. Although the parents of the affected children were no longer available for analysis, their apparently normal phenotypes were surmised from familial verbal descriptions corresponding to normal mental behaviour and phenotype. In this situation, the familial component of mutation transmission might be caused by gonadal mosaicism of a MED13L mutation in a gonad from either the father or the mother. The case reports and the literature review presented in this manuscript can be useful for genetic counselling.
Assuntos
Deficiência Intelectual , Complexo Mediador , Humanos , Deficiência Intelectual/genética , Complexo Mediador/genética , FenótipoRESUMO
PURPOSE: A case-control study was done to confirm the higher prevalence of sensorineural hearing loss (SNHL) among sickle cell patients (HbSS) from southern Brazil. PATIENTS AND METHODS: Twenty-eight patients and 28 matched normal controls were studied. Besides complete anamneses and physical otolaryngological examination, all individuals had audiometric and tympanometric testings to determine the presence of SNHL or middle ear problems. The only significant difference between groups was the presence of a positive history of otologic symptoms (hearing loss, dizziness or tinnitus) and neurological sequelae in the HbSS patients. RESULTS: Six patients (21.4%) presented with SNHL compared with one control (3.6%) (Fisher's one-tailed P = .05; OR, 7.36 (95% CI, 0.82, 65.83). The average age of HbSS diagnosis was higher among the patients with SNHL (10 years +/- 8.3) than those without SNHL (5.43 years +/- 5.65), but this was not significant (analysis of variance P > .05). More patients 25 years and older on the examination date had SNHL than younger patients (Fisher's 2-tailed P < .05). Sixty-seven percent of the patients with SNHL had alterations in the acoustic reflex, and a surprising 27% of the patients without NSHL also presented with some elevation or an absence of acoustic reflex. CONCLUSIONS: These data indicate that patients with HbSS from southern Brazil are more predisposed to the development of sensorineural hearing problems than the general population.
Assuntos
Anemia Falciforme/epidemiologia , Perda Auditiva Neurossensorial/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Brasil/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Comorbidade , Feminino , Humanos , Masculino , Prevalência , Medição de Risco , Distribuição por Sexo , Estatísticas não ParamétricasRESUMO
The flexible approach to tympanoplasty has been found to be adaptable to various forms of pathologic conditions found in the temporal bone, including inflammation and infection, congenital stenosis, benign and malignant tumors, and traumatic injuries. This approach finds its best indication among all pathologic conditions in the temporal bone, in the surgical treatment of otitis media, and its sequelae. A procedure conceived to treat this dynamic process must be adaptable to new circumstances and new findings and be ready to manage unexpected situations. The flexible tympanoplasty is a step-wise approach designed to explore the contents of the middle ear methodically and in the process disclose, confirm, and often treat disease.