Rare coding variants involving MYO7A and other genes encoding stereocilia link proteins in familial meniere disease.

The MYO7A gene encodes a motor protein with a key role in the organization of stereocilia in auditory and vestibular hair cells. Rare variants in the MYO7A (myosin VIIA) gene may cause autosomal dominant (AD) or autosomal recessive (AR) sensorineural hearing loss (SNHL) accompanied by vestibular dysfunction or retinitis pigmentosa (Usher syndrome type 1B). Familial Meniere's disease (MD) is a rare inner ear syndrome mainly characterized by low-frequency sensorineural hearing loss and episodic vertigo associated with tinnitus. Familial aggregation has been found in 6-8% of sporadic cases, and most of the reported genes were involved in single families. Thus, this study aimed to search for relevant genes not previously linked to familial MD. Through exome sequencing and segregation analysis in 62 MD families, we have found a total of 1 novel and 8 rare heterozygous variants in the MYO7A gene in 9 non-related families. Carriers of rare variants in MYO7A showed autosomal dominant or autosomal recessive SNHL in familial MD. Additionally, some novel and rare variants in other genes involved in the organization of the stereocilia links such as CDH23, PCDH15 or ADGRV1 co-segregated in the same patients. Our findings reveal a co-segregation of rare variants in the MYO7A gene and other structural myosin VIIA binding proteins involved in the tip and ankle links of the hair cell stereocilia. We suggest that recessive digenic inheritance involving these genes could affect the ultrastructure of the stereocilia links in familial MD.

Prognostic impact of CD133 expression in Endometrial Cancer Patients.

To assess the impact of CD133 expression on the prognosis of endometrioid endometrial carcinoma (EEC). We retrospectively assessed CD133 expression in tissue microarray of 116 surgically treated FIGO I-III EEC. Tumors with ≥10% of CD133-expressing cells were considered CD133-positive (CD133+). On the basis of CD133 expression, clinical and pathological parameters, progression-free survival (PFS) and overall survival (OS) were evaluated. Of the EEC studied 85.2% showed CD133-expressing cells. Only 61% (n = 66) of EEC presented ≥10% of CD133 expressing cells and were considered CD133+. The mean OS for CD133+ tumour patients was 161 months (95% CI, 154-168) as compared with 146 months (95% CI, 123-160) for those with CD133- tumors (p = 0.012). The mean PFS for CD133+ tumour was 159 months (95% CI, 149-168) as compared with 147 months (95% CI, 132-161) in those with a CD133-tumour (p = 0.014). CD133+ tumours were less likely to have vascular invasion (p = 0.010) and more likely to be well differentiated (p = 0.034). C133+ tumours predicted favorable OS and PFS of EEC patients, with a Hazard Ratio 4.731 (95% CI, 1.251-17.89; p = 0.022). CD133+ tumor status correlates with favorable prognosis of EEC. Our findings are in agreement with studies addressing brain and colorectal tumours.

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

OBJECTIVES: To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. DESIGN: A cross-sectional study with a two-step cluster analysis. SETTINGS: A tertiary referral multicenter study. PARTICIPANTS: Nine hundred and eighty-eight adult patients with unilateral MD. MAIN OUTCOME MEASURES: best predictors to define clinical subgroups with potential different aetiologies. RESULTS: We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. CONCLUSIONS: Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials.

Prevalence of anti-rubella, anti-measles and anti-mumps IgG antibodies in neonates and pregnant women in Catalonia (Spain) in 2013: susceptibility to measles increased from 2003 to 2013.

Non-immune neonates and non-immune pregnant women are at risk of developing rubella, measles and mumps infections, including congenital rubella syndrome. We describe the seroepidemiology of measles, mumps and rubella (MMR) in neonates and pregnant women in Catalonia (Spain). Anti-rubella, anti-measles and anti-mumps serum IgG titres were assessed using enzyme-linked immunosorbent assay (ELISA) tests in 353 cord blood samples from neonates of a representative sample of pregnant women obtained in 2013. The prevalence of protective antibody titres in neonates was 96 % for rubella IgG (≥8 IU/ml), 90 % for measles IgG (>300 IU/ml) and 84 % for mumps IgG (>460 EU/ml). Slightly lower prevalences of protective IgG titres, as estimated from the cord blood titres, were found in pregnant women: 95 % for rubella IgG, 89 % for measles IgG and 81 % for mumps IgG. The anti-measles and anti-mumps IgG titres and the prevalences of protective IgG titres against measles and mumps increased significantly (p < 0.001) with maternal age. The prevalence of protective anti-measles IgG titres decreased by 7 % [odds ratio (OR) = 0.15, p < 0.001), the prevalence of protective anti-rubella IgG titres increased by 3 % (OR = 1.80, p < 0.05) and the MMR vaccination coverage (during childhood) in pregnant women increased by 54 % (OR = 2.09, p < 0.001) from 2003 to 2013. We recommend to develop an MMR prevention programme in women of childbearing age based on mass MMR vaccination or MMR screening and vaccination of susceptible women to increase immunity levels against MMR.

Familial clustering and genetic heterogeneity in Meniere's disease.

The aims of this study were to estimate the prevalence of familial cases in patients with Meniere's disease (MD) and to identify clinical differences between sporadic and familial MD. We recruited 1375 patients with definite MD according to the American Academy of Otolaryngology-Head and Neck Surgery criteria, obtaining the familial history of hearing loss or episodic vertigo by direct interview or a postal survey in 1245 cases in a multicenter study. Familial clustering was estimated by the recurrence risk ratio in siblings (λs ) and offspring (λo ) using intermediate and high prevalence values for MD in European population. A total of 431 patients (34%) reported a familial history of hearing loss or recurrent vertigo and 133 patients had a relative with possible MD. After clinical reevaluation, 93 relatives in 76 families were diagnosed of definite MD (8.4%), including three pairs of monozygotic twins. λs and λo were 16-48 and 4-12, respectively. We observed genetic heterogeneity, but most families had an autosomal dominant inheritance with anticipation. No clinical differences were found between sporadic and familial MD, except for an early onset in familial cases. We may conclude that MD has a strong familial aggregation and that sporadic and familial MDs are clinically identical.

[Benign paroxysmal positional vertigo of the horizontal canal: A multicenter study]. / Estudio multicéntrico en pacientes con vertigo posicional paroxístico benigno del canal horizontal.

OBJECTIVE: BPPV localized in the horizontal semicircular canal is an infrequent entity. Nowadays there are controversies about the different treatments available. The objective of this study is to present our results. MATERIAL AND METHODS: A multicenter and retrospective study was performed in 31 patients diagnosed of BPPV-HSC between January 1996 and May 2004. RESULTS: cupulolithiasis was diagnosed in 48% on the patients. Symptoms disappeared before signs (p<0.05). Global cure rate was 85%, while relapses were 16% at one year. No relations were found between cure rate and relapses and age, gender, duration of symptoms, canalithiasis and cupulolithiasis. CONCLUSION: Our results support that there are not differences between the treatments performed in the BPPV-HSC. Symptoms disappeared before signs when canalith repositioning particles (CRP) maneuver was performed.

[Superficial siderosis of the central nervous system: report of two new cases]. / Siderosis superficial del sistema nervioso central: descripción de dos nuevos casos.

INTRODUCTION: Superficial siderosis of the central nervous system (CNS) is a rare disease characterized by deafness, ataxia and pyramidal dysfunction. It is due to hemosiderin deposition in the subpial membranes of the brain, spinal cord and cranial nerves. Most cases are secondary to chronic or recurrent bleeding into the subarachnoid space. Diagnosis is permitted by magnetic resonance imaging (MRI). CASE REPORTS: We report two patients with a chronic, slowly progressive cerebellar ataxia and hearing loss. MRI showed T2 hypointense signals in the brain, cerebellum and spinal cord diagnostic of superficial siderosis of the CNS. Xanthochromia was present in one patient. Evoked potentials showed retrochoclear hearing loss. Extensive vascular studies were negative for bleeding sources. One patient, treated with oral anticoagulants, benefited from reduction of the International Normalized Ratio. CONCLUSION: Due to its rarity, clinical suspicion is essential for diagnosis of superficial siderosis of the CNS.