A founder TMIE mutation is a frequent cause of hearing loss in southeastern Anatolia.

Using Affymetrix 10K arrays, we searched for regions of homozygosity in 51 Turkish families including at least three members with either congenital or prelingual autosomal recessive non-syndromic sensorineural hearing loss (ARNSSNHL), and identified four families whose deafness mapped to the DFNB6 locus on 3p21 containing the TMIE gene. Mutation analysis revealed the p.R84W mutation in all four families. Screening of this mutation in 254 families with ARNSSNHL, without GJB2 mutations, revealed four additional affected families. A novel mutation was found in a non-complementary marriage between a deaf couple who were homozygous for p.R84W and p.W57X, respectively with two affected children who were compound heterozygotes. Six of the TMIE families originated from southeastern Anatolia, making p.R84W a common cause of hearing loss in that region with a relative frequency of 10.3% (95% CI is 2.5-18.1%). The overall prevalence of the p.R84W mutation in ARNSSNHL in Turkey is 2.4% (95% CI is 0.7-4.0%). Genotyping of single-nucleotide polymorphisms flanking the TMIE gene revealed a conserved haplotype, suggesting a single origin for p.R84W from a common ancestor 1250 years ago (95% CI is 650-2500 years). We conclude that p.R84W could be a common mutation in other Middle Eastern populations and should be included in mutation screening offered to individuals with ARNSSNHL.

Homozygous FGF3 mutations result in congenital deafness with inner ear agenesis, microtia, and microdontia.

Homozygous mutations in the fibroblast growth factor 3 (FGF3) gene have recently been discovered in an autosomal recessive form of syndromic deafness characterized by complete labyrinthine aplasia (Michel aplasia), microtia, and microdontia (OMIM 610706 - LAMM). In order to better characterize the phenotypic spectrum associated with FGF3 mutations, we sequenced the FGF3 gene in 10 unrelated families in which probands had congenital deafness associated with various inner ear anomalies, including Michel aplasia, with or without tooth or external ear anomalies. FGF3 sequence changes were not found in eight unrelated probands with isolated inner ear anomalies or with a cochlear malformation along with auricle and tooth anomalies. We identified two new homozygous FGF3 mutations, p.Leu6Pro (c.17T>C) and p. Ile85MetfsX15 (c.254delT), in four subjects from two unrelated families with LAMM. The p.Leu6Pro mutation occurred within the signal site of FGF3 and is predicted to impair its secretion. The c.254delT mutation results in truncation of FGF3. Both mutations completely co-segregated with the phenotype, and heterozygotes did not have any of the phenotypic findings of LAMM. Some affected children had large skin tags on the upper side of the auricles, which is a distinctive clinical component of the syndrome. Enlarged collateral emissary veins associated with stenosis of the jugular foramen were noted on computerized tomographies of most affected subjects with FGF3 mutations. However, similar venous anomalies were also detected in persons with non-syndromic Michel aplasia, suggesting that a direct causative role of impaired FGF3 signaling is unlikely.

Visualization of the normal appendix in children by non-contrast MDCT.

OBJECTIVE: We studied the proportion of normal appendices, identified on non-contrast MDCT scans of the abdomen and pelvis in children with possible renal stones. MATERIALS AND METHODS: A total of 105 patients were included in the study, comprising 40 girls (38%) and 65 (62%) boys, with a mean age of 7.3 years. Non-enhanced abdominal computed tomographies were evaluated retrospectively, and the visualization, location, contents, diameter of the appendix, and the amount of abdominal fat were recorded. RESULTS: The appendix was clearly distinguished in 72 patients (68.5%). The difference in appendix visualization rates between patients with low and medium amounts of abdominal fat was statistically significant (p < 0.001). Visualization increased with age. The greatest external diameter was between 2.8 and 10 mm, with a mean of 5 +/- 1.34 mm. CONCLUSION: MDCT without contrast will be more useful when used in patients of 6 years old and over, for visualization of the appendix. A better visualization of retrocaecal appendix by MDCT provides a greater advantage over US. Prospective comparative studies will determine the role of this method in the diagnosis of acute appendicitis in pediatric patients.