PurposeAutosomal recessive non-syndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity with reported mutations in 58 different genes. This study was designed to detect deafness causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES).MethodsAfter excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador and Puerto Rico to screen for mutations in all known ARNSD genes.ResultsWe detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%) and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes suggesting founder effects.ConclusionWe report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.

The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg (SOX10 and MITF), Kallmann (CHD7 and SOX10), Noonan/LEOPARD (PTPN11), CHARGE (CHD7), or Kabuki (KMT2D). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies.

The mean platelet volume (MPV), red cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR) comprise laboratory markers in ankylosing spondylitis (AS). There is a controversy in the literature regarding which type of ear involvement is characteristic of AS. The aim of this study was to simultaneously investigate the MPV, RDW, platelet to lymphocyte (PLR) and NLR in patients with AS and their relationships with high-frequency hearing thresholds. Thirty patients with AS and 35 age-matched healthy subjects were included. Each subject was tested with low- (250, 500, 1000 and 2000 Hz) and high- (4000, 8000, 10,000, 12,000, 14,000 and 16,000 Hz) frequency audiometry. Additionally, the case and control groups were evaluated regarding the average hearing thresholds in bone conduction. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured. The RDW, MPV, neutrophils, lymphocytes and platelet counts were evaluated with the complete blood count. Furthermore, the NLR and PLR were calculated. The complete blood count, platelet numbers, ESR, CRP and NLR levels were significantly increased in the AS patients compared with the healthy controls (p < 0.001, p = 0.007, p < 0.001, p < 0.001 and p = 0.047, respectively). There was no statistically significant difference in the RDW, PLR or MPV levels (p > 0.05) in the AS patients compared with the healthy controls. The BASDAI score and disease duration were not correlated with the ESR, CRP levels, MPV, PLR, RDW or NLR in patients with AS (all; p > 0.05). The AS patients had increased average measurement values for the hearing threshold in both ears at frequencies of 250, 500, 1000 and 2000 Hz; however, there was no statistically significant difference (p > 0.05). The average values of the hearing threshold in both ears at the high frequencies of 4000, 6000, 8000, 10,000, 12,000 and 14,000 Hz were significantly increased in the case group; however, it was not significantly increased at 16,000 Hz. The current study is the first to investigate the PLR, NLR, MPV and RDW levels in acute AS. We identified a significantly increased NLR, leukocyte count, ESR and CRP in AS patients. Sensorineural hearing loss, especially at extended high frequencies, is common in patients with AS and may represent an extra-articular feature of the disease. The combined use of NLR with the leukocyte count and other clinical assessments may facilitate the diagnostic process of ankylosing spondylitis.

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