Nermin Baserer

Frequencies of gap- and tight-junction mutations in Turkish families with autosomal-recessive non-syndromic hearing loss

Mutations in genes encoding gap‐ and tight‐junction proteins have been shown to cause distinct forms of hearing loss. We have now determined the GJB2[connexin 26 (Cx26)] mutation spectrum in 60 index patients from mostly large Turkish families with autosomal‐recessive inherited non‐syndromic sensorineural hearing loss (NSSHL). GJB2 mutations were found in 31.7% of the families, and the GJB2–35delG mutation accounted for 73.6% of all GJB2 mutations. The carrier frequency of GJB2–35delG in the normal Turkish population was found to be 1.17% (five in 429). In addition to the described W24X, 233delC, 120delE and R127H mutations, we also identified a novel mutation, Q80R, in the GJB2 gene. Interestingly, the Q80R allele was inherited on the same haplotype as V27I and E114G polymorphisms. As little is known about the mutation frequencies of most other recently identified gap‐ and tight‐junction genes as a cause for hearing loss, we further screened our patients for mutations in GJB3 (Cx31), GJA1 (Cx43), ΔGJB6–D13S1830 (Cx30) and the gene encoding the tight‐junction protein, claudin 14 (CLDN14). Several novel polymorphisms, but no disease‐associated mutations, were identified in the CLND14 and GJA1 genes, and we were unable to detect the ΔGJB6–D13S1830 deletion. A novel putative mutation, P223T, was found in the GJB3 gene in heterozygous form in a family with two affected children. Our data shows that the frequency of GJB2 mutations in Turkish patients with autosomal‐recessive NSSHL and the carrier rate of the GJB2–35delG mutation in the Turkish population, is much lower than described for other Mediterranean countries. Furthermore, mutations in other gap‐ and tight‐junction proteins are not a frequent cause of hearing loss in Turkey.

Does the addition of hyperbaric oxygen therapy to the conventional treatment modalities influence the outcome of sudden deafness

OBJECTIVE : To investigate the therapeutic effects of the addition of hyperbaric oxygen (HBO) therapy to the conventional therapies in sudden deafness (SD) and to investigate the influence of patient age on the effectiveness of HBO therapy. STUDY DESIGN AND SETTING : We undertook a retrospective review of 50 cases of SD treated at a tertiary university hospital. Twenty-five patients (group 1) were treated with betahistine hydrochloride, prednisone, and daily stellate ganglion block. A second group (group 2) of 25 patients received the same basic treatment with the addition of HBO therapy. RESULTS : The mean hearing gain was 20.0 dB in group 1 and 37.9 dB in group 2 (P < 0.05). In group 2 patients, the mean gains were 51.4 and 23.3 dB for those younger and older than 50 years (P < 0.05) and 48.9 and 14.5 dB for those younger and older than 60 years (P < 0.001), respectively. In patients older than 60 years, the mean gains were 14.5 and 14.4 dB in group 2 and group 1, respectively (P > 0.05). CONCLUSIONS : The addition of HBO therapy to the conventional treatment significantly improves the outcome of SD, especially in patients younger than 50 years. Additional HBO therapy provides limited benefit in patients older than 50 years and no benefit in patients older than 60 years.

Incidence of Cochlear Involvement in Hyperbilirubinemic Deafness

Neonatal hyperbilirubinemia remains an important cause of childhood deafness, especially in developing countries. After neonatal hyperbilirubinemia, the auditory neural pathways, cochlea, or both may be affected. In this study, we aimed to determine the incidence of cochlear impairment and the appropriate means of hearing screening in hyperbilirubinemic neonates. A retrospective review of 1,032 pediatric patients with hearing loss revealed 67 cases (6.5%) of severe hyperbilirubinemia in the neonatal period. Thirty of these patients had neonatal hyperbilirubinemia as the single identifiable risk factor for hearing loss. In 26 of 30 cases (87%), otoacoustic emissions (OAEs) were absent, whereas in the remaining 4 cases (13%), robust emissions were detected despite an absent auditory brain stem response (ABR). Auditory screening of newborns with jaundice by OAEs possesses a significant risk of undiagnosed deafness. On the other hand, if the ABR is used as the single means of screening, auditory neuropathic conditions will probably be underlooked. Therefore, we recommend dual screening of hearing by ABR and OAEs in hyperbilirubinemic newborns.

MYO15A (DFNB3) mutations in Turkish hearing loss families and functional modeling of a novel motor domain mutation.

Myosin XVA is an unconventional myosin which has been implicated in autosomal recessive nonsyndromic hearing impairment (ARNSHI) in humans. In Myo15A mouse models, vestibular dysfunction accompanies the autosomal recessive hearing loss. Genomewide homozygosity mapping and subsequent fine mapping in two Turkish families with ARNSHI revealed significant linkage to a critical interval harboring a known deafness gene MYO15A on chromosome 17p13.1‐17q11.2. Subsequent sequencing of the MYO15A gene led to the identification of a novel missense mutation, c.5492G → T (p.Gly1831Val) and a novel splice site mutation, c.8968 − 1G → C. These mutations were not detected in additional 64 unrelated ARNSHI index patients and in 230 Turkish control chromosomes. Gly1831 is a conserved residue located in the motor domains of the different classes of myosins of different species. Molecular modeling of the motor head domain of the human myosin XVa protein suggests that the Gly1831Val mutation inhibits the powerstroke by reducing backbone flexibility and weakening the hydrophobic interactions necessary for signal transmission to the converter domain.

Management of Carotid Artery Invasion in Advanced Malignancies of Head and Neck Comparison of Techniques

The objective of this study was to retrospectively investigate a single institutions experience with carotid artery resection performed as part of an oncological procedure and to determine acute and convalescent complication and survival rates. We performed a record review of 28 patients with head and neck malignancy invading the carotid artery. Immediate carotid artery resection and ligation on an emergent basis was performed on 12 patients (group 1), elective resection and ligation was performed on 8 patients (group 2), and elective resection and revascularization was performed on 8 patients (group 3). In group 1, although 1 patient survived for 1 year and 1 patient survived for 2 years, 1 patient died of severe neurologic deficit, 2 patients experienced neurologic deficit with good recovery, and 1 patient was moderately disabled. In group 2, 2 patients survived without disease for 5 years, and 2 patients experienced neurologic deficit, 1 with good recovery and the other with complete recovery. In group 3, only 1 patient survived for 5 years, and within this group, 1 patient died of severe neurologic deficit, 1 patient had neurologic deficit with moderate recovery, and 1 patient had neurologic deficit with complete recovery. No significant difference in mortality and morbidity rate was observed between the “resection and ligation” group and the “resection and revascularization” group (p = .52, χ2 = 0.79). We conclude that the surgical treatment of patients with an invaded carotid artery, including carotid resection, provides a small but real chance of 5-year survival. The methods of carotid resection and repair should be guided by clinical presentation and by preoperative and intraoperative investigations.

An indolent course of multiple myeloma mimicking a solitary thyroid cartilage plasmacytoma

Multiple myeloma, solitary plasmacytoma, and extramedullary plasmacytoma constitute a continuum of a disease spectrum, which is called plasma cell neoplasms. These three entities can not be differentiated from each other on a histological basis and, for this reason, clinical evaluation is important in their differential diagnoses. Differential diagnosis guides the proper planning of treatment and helps in estimation of survival. Multiple myeloma located within the larynx is very rare. Because of its rarity, any established diagnostic and treatment criteria do not exist. In this report, a case of laryngeal multiple myeloma is presented for its extraordinary presentation and also for educational purposes.

A novel homozygous COL11A2 deletion causes a C-terminal protein truncation with incomplete mRNA decay in a Turkish patient†

Recessive mutations in COL11A2 (collagen, type XI, alpha 2), are responsible for otospondylomegaepiphyseal dysplasia (OSMED) and non‐syndromic hearing loss while dominant mutations are associated with Stickler type III, isolated cleft palate, Robin sequence, non‐ophthalmic Stickler syndrome, early onset osteoarthritis and autosomal dominant hearing loss. We describe here the clinical findings of two Turkish cousins with OSMED carrying a novel homozygous truncating mutation in exon 38 of COL11A2 gene, c.2763delT, identified on cDNA and confirmed at gDNA. This mutation is located on triple helix repeat domain of the collagen alpha‐2(XI) chain, where the majority of the previously identified mutations are located. Real‐time RT‐PCR experiment provided that mutated transcript does not decay completely. Although our analysis displays the partial survival of the mutant transcript from blood tissue, not from cartilage, we propose that this mechanism may play an important role on the variable expressivity of the heterozygous COL11A2 gene mutations.

The Place of Conservation Surgery for T3 Laryngeal Carcinomas With Fixation

Although the traditional surgical treatment of T3 laryngeal carcinomas is total laryngectomy, we have obtained favorable survival results for selected cases with partial laryngectomy, as exemplified in the literature. Extending the indications up to ultimate limits by partial, but radical surgical techniques is the recent trend in the world, for the conservation surgery of laryngeal cancers. The primary treatment of T3 laryngeal cancers, instead of irradiation, should be surgical and, for select cases partial laryngectomy, depending on laryngeal embryological development and lymphatic drainage, may be carried out. We have performed partial laryngectomy with elective or therapeutic and radical or modified radical neck dissection for 43 T3 laryngeal carcinomas at the Department of Otolaryngology, Istanbul Medical Faculty, University of Istanbul in the years 1978-1991 and obtained 2, 3, and 5 years of survival rates, which are 89, 79.4, and 73%, respectively.