AZOOR con edema discal unilateral: informe de un caso atípico / AZOOR with unilateral disc edema: An atypical case report

El diagnóstico de retinopatía aguda zonal oculta externa (AZOOR) se presenta como un desafío en la práctica del oftalmólogo. En esta enfermedad fueron descritos varios hallazgos atípicos, pero el edema del disco óptico es raro. Pretendemos describir un diagnóstico desafiador de AZOOR. Presentamos el caso de una mujer de 19 años con pérdida de visión del ojo derecho, sin dolor, con 2 semanas de evolución. El fondo de ojo presentaba edema con hiperemia del disco óptico y la campimetría demostraba una mancha ciega aumentada. Se ha considerado como diagnóstico neuritis óptica, sin causa infecciosa, por lo que ha realizado tratamiento con corticoide. Después de 4 meses, la agudeza visual había mejorado, pero persistían las alteraciones en la campimetría con hiperautofluorescencia alrededor del disco óptico. La tomografía óptica de coherencia demostró pérdida generalizada de las capas externas de la retina y disminución de la reflectancia de la región correspondiente. Se concluye que el edema de la papila no es un hallazgo frecuente de AZOOR, por lo que representa una enfermedad de difícil diagnóstico (AU)

Acute zonal occult outer retinopathy (AZOOR) diagnosis is challenging and frequently delayed. Atypical findings were described, nevertheless optic disc edema has not been consistently reported. In this study we pretend to describe a challenging diagnosis of AZOOR. In our case, a 19-year-old female presented painless vision loss in her right eye for 2 weeks. Fundus examination revealed optic disc hyperaemic edema and the visual field (VF) an enlarged blind spot. Non-infectious optic neuritis was assumed and intravenous corticotherapy administered. Four months later, VA had improved, but a VF defect persisted. Funduscopic examination showed mild peripapillary atrophy and autofluorescence zonal hyperautofluorescence around optic disc. Optical coherence tomography demonstrated diffuse loss of outer retinal layers and electroretinogram weakened signal at the corresponding region. In conclusion, unilateral optic disc edema, generally not associated with AZOOR typical presentation, hamper an early diagnosis and expresses this case relevance (AU)

AZOOR with unilateral disc edema: An atypical case report.

Acute zonal occult outer retinopathy (AZOOR) diagnosis is challenging and frequently delayed. Atypical findings were described, nevertheless optic disc edema has not been consistently reported. In this study we pretend to describe a challenging diagnosis of AZOOR. In our case, a 19-year-old female presented painless vision loss in her right eye for 2 weeks. Fundus examination revealed optic disc hyperaemic edema and the visual field (VF) an enlarged blind spot. Non-infectious optic neuritis was assumed and intravenous corticotherapy administered. Four months later, VA had improved, but a VF defect persisted. Funduscopic examination showed mild peripapillary atrophy and autofluorescence zonal hyperautofluorescence around optic disc. Optical coherence tomography demonstrated diffuse loss of outer retinal layers and electroretinogram weakened signal at the corresponding region. In conclusion, unilateral optic disc edema, generally not associated with AZOOR typical presentation, hamper an early diagnosis and expresses this case relevance.

Streptococcus pneumoniae prevalence in nasopharynx, oropharynx and gingival sulcus in Brazilian adults:A preliminary study.

AIM: This study aimed to evaluate the prevalence of S. pneumoniae colonization in three different sites in healthy adults: nasopharynx, oropharynx and gingival sulcus. METHODS: Two-hundred and sixty five adults, aged 20-60 years, who attended dental clinics in one public university (n = 106) and one military institution (n = 159) were enrolled in this study. Pneumococcal detection was performed by direct culture (DC) and PCR for lytA gene after a broth enrichment step. Capsular types were determined by sequential multiplex PCR. RESULTS: We identified 18 (6.8%) pneumococcal carriers among 265 adults by PCR, but only one (0.4%) pneumococcal strain was isolated by DC method. Oropharynx (17; 6.4%) was the main source of S. pneumoniae. Colonization of gingival sulcus and nasopharynx was found in 4 (1.5%) and 2 (0.8%) adults, respectively. Nine distinct capsular types were detected from 9 adults and co-colonization with 2 serotypes was confirmed in 4 (1.5%) subjects. Factors associated with carriage were being females, low level of schooling, non-military and regular medication. We observed a low (6.8%) pneumococcal carriage prevalence, but oropharyngeal samples yielded more sensitive results, especially by the PCR-based detection methodology. CONCLUSION: Gingival sulcus was found to be a possible reservoir for S. pneumoniae independently of the oropharynx or nasopharynx colonization.

Cardiac surgery in infective endocarditis and predictors of in-hospital mortality. / Cirurgia cardíaca na endocardite infeciosa e preditores da mortalidade intra­hospitalar.

INTRODUCTION: Infective endocarditis (IE) is a serious disease with significant in-hospital mortality (15-30%) despite advances in medical and surgical therapy. AIMS: To perform a clinical characterization of patients undergoing cardiac surgery for IE and to identify factors that predict in-hospital mortality. METHODS: We retrospectively analyzed 145 patients with IE admitted between January 2006 and October 2017. RESULTS: The median age was 72 years. IE was acquired mainly in the community (69%), and involved the native aortic valve in 54% of patients, biological prosthetic valves in 22.1% and mechanical valves in 10.3%. Staphylococcus spp. (31.0%) were the most frequent etiological agents. Cardiac surgery was emergent in 29 patients, urgent in 108, and elective in eight. The main indications were heart failure (57.9%), large vegetations (20%), systemic embolism (17.2%) and valve dysfunction (15.2%). Overall, biological valves were implanted in 62.1% of patients and mechanical valves in 37.2%. A total of 19 patients (13.1%) died. Predictors of mortality were preoperative atrial fibrillation and lower left ventricular ejection fraction, postoperative severe valve regurgitation associated with cardiogenic shock, sepsis, septic shock associated with cardiogenic shock, cardiac tamponade, need for renal replacement therapy and, although without statistical significance, emergent surgery. CONCLUSIONS: There is a need for better indicators to enable early identification of surgical candidates for IE, implementation of a heart team, and better surgical strategies, including more rapid intervention, more specific postoperative care, and optimal antibiotic therapy.

Evaluation of bone texture imaging parameters on panoramic radiographs of patients with Sheehan's syndrome: a STROBE-compliant case-control study.

Sheehan's syndrome (SHS) is a rare condition related to the risk of osteoporosis and evaluation of bone texture imaging features on panoramic radiographs would be suitable for this condition, which was the aim of the present study. Fractal dimension, lacunarity, and trabecular morphologic aspects were significantly altered in these patients. INTRODUCTION: SHS is an important public health problem particularly in developing countries. It is characterized as postpartum hypopituitarism secondary to obstetric complications-related ischemic pituitary necrosis that shows significant systemic metabolic repercussions. Thus, this study aimed to evaluate bone texture parameters in digital panoramic radiographs of patients with SHS. METHODS: A case-control study was conducted with 30 SHS patients from an Endocrinology and Diabetology Service of reference in Brazil, and 30 age- and sex-matched healthy controls. A custom computer program measured fractal dimension, lacunarity, and some morphologic features in the following mandibular regions of interest (50 × 50 pixels): below the mental foramen (F1), between the first and second molars (M1), and at the center of the mandibular ramus (R1). RESULTS: The fractal analysis showed a statistically significant difference between the studied groups in all regions of interest. The fractal dimension in F1 (p = 0.016), M1 (p = 0.043), and R1 (p = 0.028) was significantly lower in SHS group, as well as lacunarity in R1 (p = 0.008). Additionally, several morphologic features were statistically significant in the SHS group (p < 0.05). CONCLUSION: Therefore, individuals with SHS showed altered imaging texture parameters on panoramic radiographs, which reflect a smaller spatial organization of the bone trabeculae and, possibly, a state of reduced mineral bone density.

Cone beam computed tomography devices in the evaluation of buccal bone in anterior teeth.

OBJECTIVE: To determine the accuracy of various cone beam computed tomography (CBCT) devices in assessing the buccal bone in anterior teeth. MATERIAL AND METHODS: A skull encased in tissue equivalent material was imaged with six CBCT devices: 3D Accuitomo 170 (J. Morita, Japan), CS 9000 3D (Carestream Dental, France), CS 9300 (Carestream Dental, France), Eagle 3D (Dabi Atlante, Brazil), i-CAT Classic (Imaging Sciences International, USA) and Orthophos XG 3D (Sirona Dental System, USA). The exposure and acquisition protocols were determined using the manufacturer's guidelines, the voxel size adjusted as close as possible to 0.2 mm. Cross-sectional images were evaluated randomly, and the buccal bone was assessed. RESULTS: The statistics were calculated based on a logistic regression model with the significance level set at 5%. All CBCT devices showed high accuracy; however, observers noted that the accuracy and sensitivity of CS 9300 device were slightly superior. CONCLUSION: The diagnostic performance of all CBCT devices was high for the evaluation of buccal bone in anterior teeth. When the clinical usefulness of an imaging modality is equivalent, the choice of appropriate imaging should be directed towards the modality that delivers the least radiation dose to the patient for a specific diagnostic task.

Characterization of a new genotype of Betapapillomavirus HPV 17 through L1, E7, E7 and LCR sequences.

Human papillomavirus (HPV) exhibits epithelial and mucosal tropism. HPV type 17 belongs to the Betapapillomavirus genus and molecular cloning experiments have identified two subtypes (17a and 17b) isolated from epidermodysplasia verruciformis (EV). HPV subtypes are characterized by dissimilarities from 2 to 10% at the nucleotide level from their referenced HPV. The aim of this study was to characterize the L1, E6, E7 and LCR sequences from an isolate, which was recovered from the oral mucosa of an asymptomatic 63 year-old woman. The whole late gene 1 (L1) was amplified using several sets of primers. The complete early genes 6 and 7 (E6, E7) and the long control region (LCR) were amplified using specific primers. Potential binding sites for transcriptional factors within the LCR were also investigated. Within these sets, the DNA sequence was altered at 91 positions (68 in L1, 13 in E6, 8 in E7, and 2 in LCR sequences). L1 analysis showed high dissimilarity compared with the HPV 17 prototype, reaching 4% of nucleotide substitutions and leading to a probable third 17 subtype. The E6 oncoprotein presented the highest modification among the sequences studied, with four amino acid changes in comparison with the prototype isolate. One amino acid was modified at a position 62 (S-T), a zinc-binding domain (CxxC(C)29 CxxC). Our findings provide data on genetic variations seen in this genotype, reaching to dichotomic branching and pointing to an evolutionary process.

Improving outcome in congenital diaphragmatic hernia - experience of a tertiary center without ECMO.

BACKGROUND: Congenital diaphragmatic hernia (CDH) has a high mortality rate, representing a therapeutic challenge. Prenatal diagnosis (PND) is essential in defining optimal perinatal strategy, particularly delivery planning. Hospital Pediátrico de Coimbra is the referral centre for all neonatal surgery, particularly CDH, for the central region of Portugal. The aim was to evaluate clinical management and outcome of newborns with CDH. METHODS: An exploratory retrospective study made up of newborns admitted to PICU with CDH was undertaken between January 1995 and December 2014. Two groups were formed based on their year of admission: group A (1995- 2004) and group B (2005- 2014) and were compared. RESULTS: The mean birth weight of the 69 newborns admitted was 2.762 ± 696 g; the median of the gestational age was 38 weeks. Associated malformations were observed in 28 (40.5%) and 15 (21.7%) had a right-sided diaphragm defect. The global mortality was 13.0%; in group A was significantly higher than in group B (22.2 vs 3.0%; p = 0.029). A reduction in mortality throughout the years was confirmed after adjusting for POS score (OR = 0.77; 95% CI: 0.62- 0.96, p = 0.021). PND was made in 30.6% of cases in the group A and 66.7% in the group B (p = 0.03). Tertiary perinatal hospital birth was achieved in 60% of newborns in the group A versus 84.8% in group B (p = 0.022). Maximum fraction of inspired oxygen showed a statistically significant difference between the two study groups (60% vs 40%; p = 0.009). CONCLUSIONS: A significant decrease in mortality was observed throughout the study. The authors highlight the increase in prenatal diagnosis and an improvement in perinatal care with planning delivery as important contributors to these results.

On the Adult Behavioral Repertoire of the Sawfly Perreyia flavipes Konow, 1899 (Hymenoptera: Pergidae): Movement, Mating, and Thanatosis.

Perreyia flavipes Konow, 1899 (Pergidae: Perreyinae) is a sawfly species with gregarious larvae commonly found in open areas in southern Brazil through Uruguay and northern Argentina. The combination of highly gregarious larvae with the production of a variety of toxins in P. flavipes has led to severe cases of intoxication in a variety of livestock species. Over the years, considerable information was discovered on the larval natural history of P. flavipes; however, virtually nothing is known about the adult behavior, particularly because of its short life-span. In this study, we report on the first extensive study on the adult behavior of P. flavipes, including movement, mating (with oviposition and maternal care), and thanatosis. Our results show some unusual behavioral adaptations presented by P. flavipes, such as irregular activity behavior (i.e., deficient gait pattern), thanatosis behavior-like display, and primitive maternal care. Individual behavioral acts are described and compared among sexes, and their potential functions are discussed.

Panoramic and skull imaging may aid in the identification of multiple myeloma lesions.

BACKGROUND: The purpose of this study was to investigate the presence of punched-out lesions in craniofacial bones using three different radiographic protocols in a large cohort of patients. MATERIAL AND METHODS: One hundred fifty-five MM patients were evaluated using panoramic and skull (frontal and lateral) radiographs, which were performed in all patients at the time of MM diagnosis. The diagnostic potential for detecting punched-out lesions was compared among the radiographic techniques. RESULTS: MM punched-out lesions were identified in 135 (87%) panoramic radiographs, 141 (91%) frontal and 144 (93%) lateral skull radiographs. Punched out-lesions were synchronously present in skull and jawbones in 129 (83.23 %) cases. The lesions were detected exclusively in skull in 18 (11.61%) cases and exclusively in jawbones in 6 (3.87%) cases. Punched out-lesion mainly affected the skull and the jawbones in a synchronous way (p<0.001) rather than separately. CONCLUSIONS: All investigated radiographic techniques (panoramic, frontal and lateral skull approaches) demonstrated high detection rates for MM punched-out lesions in craniofacial bones. Panoramic radiography may aid to the radiographic protocols to identify multiple myeloma bone lesions.

Cone beam computed tomography assessment of the pterygomaxillary region and palatine canal for Le Fort I osteotomy.

The aim of this study was to evaluate the anatomical linear measurements of the descending palatine canal and the pterygomaxillary fissure for Le Fort I preoperative planning. Seventy-five patients, comprising 46 females (61.3%) and 29 males (39.7%), underwent multi-slice computed tomography examinations performed for preoperative orthognathic surgical planning. The images were categorized according to sex, craniofacial side, and skeletal and craniofacial patterns. The anterior length between the descending palatine canal and the lateral wall of the piriform rim showed a higher mean value for males compared to females (P=0.0121). The posterior distance also showed a difference between the sexes and the highest mean was observed in females (P=0.0295). Comparing the posterior width for the skeletal patterns, a statistical difference was observed between classes I and III (P=0.0371), and classes II and III (P=0.0094). Regarding the craniofacial patterns, the brachycephalic (P=0.0078) and mesocephalic (P=0.0015) groups showed a greater posterior width in females. In conclusion, the patient's sex and aspects of the skeletal pattern and craniofacial pattern have an influence on the pterygomaxillary area and descending palatine canal anatomy. A preoperative computed tomography analysis involving this evaluation could reduce the risk of surgical complications.

Pneumococcal nasopharyngeal carriage among children in Brazil prior to the introduction of the 10-valent conjugate vaccine: a culture- and PCR-based survey.

We performed two different approaches (broth enrichment step prior to culture (BEC) and PCR (BEPCR)) for detecting Streptococcus pneumoniae from nasopharyngeal specimens collected from 242 children aged <6 years attending one hospital (n = 140) and one childcare centre (n = 102) in a major urban area in Brazil. These specimens were collected immediately before the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) and the 13-valent vaccine (PCV13) for routine use in Brazil. Results were compared with previous findings obtained with direct culture (DC) on a selective medium. Colonisation prevalence was 58·3% (n = 141), being higher among children attending the childcare centre (62·7% vs. 55%). The culture-based methods (DC and BEC) enabled the detection of S. pneumoniae in 119 (49·2%) and 115 (47·5%) children, respectively. The PCR-based method (BEPCR) was more sensitive and 137 (56·6%) carriers were identified. Twenty-six serogroups/serotypes were identified, predominantly 6B, 19F, 14, 6A, 15C and 23F. Multiple colonisation was observed in 13 (5·4%) children. The estimated serotypes coverage of available PCVs was 40·4% for the 10-valent (included in the Brazilian immunisation programme) and 55·8% for the 13-valent (only available in private clinics). The use of robust approaches to obtain a more realistic insight about the asymptomatic carrier status is of paramount importance to estimate and assess the impact of vaccine implementation. The combination between culture-based and molecular methods constitutes a suitable strategy.

Late reproductive analysis in rat male offspring exposed to nicotine during pregnancy and lactation.

We previously observed that nicotine, administered to rats (Wistar) during pregnancy and lactation periods, provokes, in the progeny, late morphofunctional alterations in Leydig cell, body weight increase in adulthood (90 days post partum, dpp) as well as seminiferous epithelium injury. Aiming to investigate whether the spermatogenic damage previously observed in adult progenies from pregnant and lactating nicotine-exposed rat dams are maintained or whether it is worsened in older rats, we analyzed the morphological testicular alterations after up to two complete periods of spermatogenesis (53 days each), spermatic parameters, and sperm DNA fragmentation. Pregnant and lactating rats were nicotine-exposed (2 mg/kg/day) through an osmotic minipump implanted on the first day of pregnancy and replaced after birth. Absolute Control (no minipump) and Sham Control (minipump without nicotine) groups were established. The offspring were killed at 90, 143, and 196 dpp. Significant alterations in morphometric and stereological testicular parameters, such as concentration of sperm number, daily sperm production, and plasma and intratesticular levels of cholesterol and testosterone were not observed in nicotine-exposed rats. Testicular histopathological analysis showed small intraepithelial vacuolization and an accentuated germ cell desquamation in exposed rats. However, the offspring from nicotine-exposed dams exhibited higher frequency of morphologically abnormal spermatozoa and lower sperm motility in comparison with control groups. In addition, nicotine-exposed groups showed a significant reduction in sperm mitochondrial activity and an increased sperm DNA fragmentation (Comet assay). These results indicate a late reproductive damage in the male progeny caused by maternal nicotine exposure, related to the decrease in sperm quality.

Vertical stratification and effect of petiole and dry leaf size on arthropod feeding guilds in Cecropia pachystachya (Urticaceae).

This study aimed to test for vertical stratification and the effects of dry leaf size on herbivore and predator arthropods and petiole length on insect borers in Cecropia pachystachya. The leaves were sampled in three strata: attached to the plant, suspended on the vegetation and on the ground. We detected vertical stratification only in the guild of predator arthropods associated with dry leaves, with lower richness and abundance in the attached stratum. In addition, larger leaves positively affected the insect herbivore fauna, whereas the richness and abundance of insect borers increased with petiole length. The greater isolation of leaves attached to trees relative to the surrounding vegetation likely creates greater difficulty for dispersal and colonization by non-winged predators such as spiders. Larger dry leaves provide more shelter against predators and climate variations for insect herbivores. Moreover, larger petioles increase the availability of resources and nesting sites for insect borers. These results are consistent with other studies that found a similarity in the structure of feeding guilds across vertical strata and with studies that showed an increase in species richness and abundance of free-feeding insect herbivores with increasing structural complexity of their host.

Overnourishment during lactation induces metabolic and haemodynamic heart impairment during adulthood.

AIM: In this study, the effects of postnatal overfeeding on heart energy homoeostasis and cardiac haemodynamics in adult male Swiss mice were examined. METHODS AND RESULTS: During the suckling period, the mice were divided into four groups of control or overfed pups in combination with baseline or ischaemia/reperfusion treatments (control group baseline, CGBL; overfed group baseline, OGBL; control group ischaemia/reperfusion, CGIR; and overfed group ischaemia/reperfusion, OGIR). End diastolic pressure (EDP), heart contraction speed (Max dP/dt), relaxation speed (Min dP/dt), isovolumetric relaxation time (Tau) and frequency by beats per minute (BPM) were measured. During baseline and ischaemia/reperfusion, key proteins such as AKT1, AKT2, AKT3, pAKT, adenosine monophosphate-activated protein kinase (AMPK), pAMPK, insulin receptor beta (IRß), protein tyrosine phosphatase 1B (PTP1B), insulin receptor substrate 1 (IRS1), fatty acid binding protein (FABP), CD36, phosphoinositide 3-kinase (PI3K) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were studied. The expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), carnitine palmitoyltransferase 1 (CPT1) and uncoupling protein 3 (UCP3) was studied as a marker of cardiac hypertrophy and energetic metabolism. Cardiac fibrosis was analyzed by quantifying collagen deposition, which is increased in the OGBL and OGIR groups compared with the control groups. CONCLUSIONS: The OGBL group showed reduced EDP compared with the CGBL group and high Max dP/dt compared with the OGBL group. Ischaemia/reperfusion increased EDP and Min dP/dt in the intragroup comparison. By contrast, Tau and frequency were not significantly different among groups. The OGIR mice showed significant alterations in heart metabolism proteins, including AKT2, pAKT/AKT1, pAKT/AKT2, AMPK, pAMPK/AMPK, PTP1B, IRS1, FABP and CD36. Furthermore, alterations in ANP, BNP, CPT1 and UCP3 messenger RNA (mRNA) expression indicated hypertrophy and reduction in their efficiency, such that exclusive overnutrition in childhood induces a long-term effect on haemodynamics, metabolism and heart remodelling.

Wolbachia spp. interfere na detecção molecular de Ehrlichia canis e Anaplasma platys em cães com microfilaremia / Wolbachia spp. interferes with molecular detection of Ehrlichia canis and Anaplasma platys in microfilaremic dogs

This report aimed to study the interference in molecular testing for Ehrlichia canis and Anaplasma platys in blood of 155 dogs from the coastal region of Rio de Janeiro. Five Anaplasmataceae positive samples but negative for E. canis and A. platys, from microfilaremic animals, were chosen for sequencing. These sequences, when compared to Gen et Bank database, showed 88% to 100% similarity with Wolbachia spp. denoting an interference in the detection of DNA from other members of Anaplasmataceae, possibly due to a high concentration of Wolbachia spp. DNA.(AU)

Iterative reconstruction of detector response of an Anger gamma camera.

Statistical event reconstruction techniques can give better results for gamma cameras than the traditional centroid method. However, implementation of such techniques requires detailed knowledge of the photomultiplier tube light-response functions. Here we describe an iterative method which allows one to obtain the response functions from flood irradiation data without imposing strict requirements on the spatial uniformity of the event distribution. A successful application of the method for medical gamma cameras is demonstrated using both simulated and experimental data. An implementation of the iterative reconstruction technique capable of operating in real time is presented. We show that this technique can also be used for monitoring photomultiplier gain variations.

Influence of the artefact reduction algorithm of Picasso Trio CBCT system on the diagnosis of vertical root fractures in teeth with metal posts.

OBJECTIVES: To assess the influence of the artefact reduction algorithm (AR) available on the Picasso Trio 3D(®) imaging system (Vatech, Hwaseong, Republic of Korea) on image quality [greyscale values, contrast-to-noise ratio (CNR) and artefact formation] and diagnosis of vertical root fractures (VRFs) in the teeth with intracanal metal posts. METHODS: 30 uniradicular teeth had their crowns removed and their roots endodontically treated to receive intracanal metal posts. In 20 teeth, both complete (n = 10) and incomplete (n = 10) VRFs were created. Each tooth was scanned twice, with and without AR activation. The mean and variation of greyscale values, as well as CNR, were calculated for all images. Subsequently, an evaluator compared the amount of artefact (cupping, white streaks and dark bands) in all images. Five evaluators rated for VRF presence using a five-point scale. RESULTS: Mean greyscale values and CNR were significantly decreased in images acquired with the AR. The usage of the algorithm promoted an overall reduction of image artefacts. Regarding the diagnosis of complete and incomplete VRFs, the use of the AR had an overall negative impact on specificity and accuracy. CONCLUSIONS: While indeed reducing artefact formation, the use of the AR, instead of improving the impact on the diagnosis of VRFs in teeth with intracanal metal posts, had a negative impact on the diagnosis.

Collagen type IV-related nephropathies in Portugal: pathogenic COL4A5 mutations and clinical characterization of 22 families.

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.