Unknown Prevalence Research Articles

ROS1-GOPC/FIG: a novel gene fusion in hepatic angiosarcoma.

Hepatic angiosarcoma (HAS) is a rare and highly lethal malignancy with few effective systemic treatments. Relatively little is known about the genetic abnormalities that drive this disease. As a result, there has been minimal progress towards applying targeted therapies to the treatment of HAS. We describe the first reported case of a patient with HAS that harbored a fusion of ROS1 with GOPC/FIG. Similar to other rearrangements involving ROS1, the resulting fusion protein is believed to act as a major driver of carcinogenesis and may be subject to inhibition by drugs that target ROS1 such as crizotinib. We then queried the MSK-IMPACT clinical sequencing cohort and cBioportal datasets, demonstrating the previously unknown prevalence of ROS1-GOPC fusions in soft tissue sarcomas and hepatobiliary cancers. Amplification of these genes was also found to correlate with reduced overall survival. This is followed by a review of the role played by ROS1 rearrangements in cancer, as well as the evidence supporting the use of targeted therapies against the resulting fusion protein. We suggest that testing for ROS1 fusion and, if positive, treatment with a targeted therapy could be considered at the time of diagnosis for patients with angiosarcoma. This report also highlights the need for further investigation into the molecular pathophysiology of this deadly disease.

Cultural Snapshots: A Method to Capture Social Contexts in Development of Prejudice and Stereotyping.

The scientific identification of how social environments transmit intergroup biases is a transparently complex endeavor. Existing research has examined the emergence of intergroup biases such as racial prejudice and stereotypes in many ways, including correlations between racial diversity and children's prejudice, content analyses of features in the media, or experiments testing the influence of selected variables with unknown prevalence in children's environments. Yet, these approaches have left unanswered how the social environments that children engage with cause them to acquire racial prejudice and stereotypes. We provide a review of the existing literature on socialization of racial prejudice and stereotypes and then present a methodological approach that can be used to quantify and test causal relations between the features of children's social environments and intergroup biases. We provide examples of how this method has and can be used alongside a discussion of unique considerations when applied to child samples.

Assessment of metabolic syndrome risk factors among rural-dwelling older adults requires innovation: partnerships and a mobile unit can help

Purpose Older adults are at risk for developing metabolic syndrome (MSX). Given the growing rural older adult population and the unknown prevalence rate of MSX in rural communities, the purpose of this paper is to assess the risk factors for MSX among rural elders. Design/methodology/approach Individuals aged 55+ from four West Alabama rural communities were assessed by an interdisciplinary healthcare team via a mobile unit (n=216). Descriptive analyses and analysis of variances (ANOVA) were conducted to assess the effect of gender, race and community on the number of risk factors of MSX among rural elders. Findings Results of a three-way ANOVA revealed a significant interaction between gender, age and community on the number of MSX risk factors [F (16,193)= 2.41, p <0.01]. Rural communities with lower social economic status (SES) and predominantly African American residents were at higher risk for developing MSX compared to communities with higher SES [F(3, 68) = 7.42, p<0.05]. Practical implications Findings suggest low SES rural communities are at risk of developing MSX. Innovative approaches such as mobile healthcare delivery are crucial to providing quality healthcare and preventive health screens to underserved rural older adult communities. Originality/value Limited research is available on assessing rural midlife and older adults at risk for metabolic syndrome largely due to lack of communication or transportation infrastructure and their history of negative experiences with public institutions. This research demonstrates that these barriers can be addressed.

Relatively high rate of postpartum thyroiditis in the Straits of Messina area. Predictivity of both postpartum thyroiditis and permanent hypothyroidism by performing, in the first trimester of gestation, thyroid ultrasonography and measurement of serum thyroperoxidase and thyroglobulin autoantibodies

The prevalence of postpartum thyroiditis (PPT) averages 5%, with a range from 1% (Thailand) to 22% (Wales, UK, and Liguria, Italy), but 3.6% in another Italian region (Puglia). Evolution of PPT into permanent hypothyroidism (PH) occurs in approximately 50% of cases. Positive thyroperoxidase autoantibodies (TPOAb) in a pregnant woman is a strong predictor of PPT. Because in previous gestational cohorts we found an approximate 12% rate of TPOAb positivity, which compares with 15% in the Liguria cohort and 6% in the Puglia cohort, we hypothesized that the currently unknown prevalence of PPT in Sicily would approximate the said Liguria prevalence. We also explored the predictive value of serum thyroglobulin Ab (TgAb) positivity and ultrasonographic signs suggestive of thyroiditis (UST) at first trimester of gestation for PPT.Of 412 pregnant women who were followed-up for 1 year after delivery, 63 (15.3%) developed PPT, and 54% of them had PH. Gestational rates of TPOAb positivity alone, TgAb positivity alone or UST were 11.4%, 7.8% or 35.0%, with associated PPT rates of 66%, 45% or 36%. TgAb assay allowed detection of 9/63 PPT women (14.3%) who were TPOAb-negative. However, TPOAb remained a better predictor compared to TgAb or UST (odds ratio = 32 vs 10 or 13). Lowering the positivity threshold for either Ab to ≥61 U/ml, Ab-positive were 23.8% of PPT women and 17.7% of pH women. UST was detected in 82.5% of women who developed PPT, precisely 88% of those who evolved into PH and 75.9% of those who did not.Ours is the second study of the new millennium showing a PPT frequency >10%. The dual Ab and lowered threshold strategy correctly predicts more cases of PPT and PH compared to the sole TPOAb strategy. We confirm that half of the PPT women will have PH.

Clinical relevance of screening checklists for detecting cancer predisposition syndromes in Asian childhood tumours

Assessment of cancer predisposition syndromes (CPS) in childhood tumours is challenging to paediatric oncologists due to inconsistent recognizable clinical phenotypes and family histories, especially in cohorts with unknown prevalence of germline mutations. Screening checklists were developed to facilitate CPS detection in paediatric patients; however, their clinical value have yet been validated. Our study aims to assess the utility of clinical screening checklists validated by genetic sequencing in an Asian cohort of childhood tumours. We evaluated 102 patients under age 18 years recruited over a period of 31 months. Patient records were reviewed against two published checklists and germline mutations in 100 cancer-associated genes were profiled through a combination of whole-exome sequencing and multiplex ligation-dependent probe amplification on blood-derived genomic DNA. Pathogenic germline mutations were identified in ten (10%) patients across six known cancer predisposition genes: TP53, DICER1, NF1, FH, SDHD and VHL. Fifty-four (53%) patients screened positive on both checklists, including all ten pathogenic germline carriers. TP53 was most frequently mutated, affecting five children with adrenocortical carcinoma, sarcomas and diffuse astrocytoma. Disparity in prevalence of germline mutations across tumour types suggested variable genetic susceptibility and implied potential contribution of novel susceptibility genes. Only five (50%) children with pathogenic germline mutations had a family history of cancer. We conclude that CPS screening checklists are adequately sensitive to detect at-risk children and are relevant for clinical application. In addition, our study showed that 10% of Asian paediatric solid tumours have a heritable component, consistent with other populations.

Seroprevalence of fourteen human polyomaviruses determined in blood donors.

The polyomavirus family currently includes thirteen human polyomavirus (HPyV) species. In immunocompromised and elderly persons HPyVs are known to cause disease, such as progressive multifocal leukoencephalopathy (JCPyV), haemorrhagic cystitis and nephropathy (BKPyV), Merkel cell carcinoma (MCPyV), and trichodysplasia spinulosa (TSPyV). Some recently discovered polyomaviruses are of still unknown prevalence and pathogenic potential. Because HPyVs infections persist and might be transferred by blood components to immunocompromised patients, we studied the seroprevalence of fourteen polyomaviruses in adult Dutch blood donors. For most polyomaviruses the observed seroprevalence was high (60–100%), sometimes slightly increasing or decreasing with age. Seroreactivity increased with age for JCPyV, HPyV6 and HPyV7 and decreased for BKPyV and TSPyV. The most recently identified polyomaviruses HPyV12, NJPyV and LIPyV showed low overall seroprevalence (~5%) and low seroreactivity, questioning their human tropism. Altogether, HPyV infections are common in Dutch blood donors, with an average of nine polyomaviruses per subject.

Genetic testing for lymphedema-distichiasis syndrome

Abstract We studied the scientific literature and disease guidelines to summarize the clinical utility of genetic testing for lymphedema distichiasis (LD) syndrome. LD is inherited in an autosomal dominant manner, and has unknown prevalence. It is caused by variations in the FOXC2 gene. Clinical diagnosis involves clinical examination, targeted at identifying primary lymphedema (chronic swelling of the extremities) and distichiasis (double row of eyelashes). The genetic test is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Non-coeliac gluten sensitivity and the spectrum of gluten-related disorders: an updated overview.

The spectrum of gluten-related disorders includes coeliac disease (CD), wheat allergy (WA) and the suggested entity of non-coeliac gluten sensitivity (NCGS). An increasing number of the world's population are avoiding gluten due to the assumption of health benefits and self-diagnosed gastrointestinal and/or extra-intestinal symptoms. Unlike CD and WA, NCGS is a relatively new entity with an unknown prevalence and mechanisms, complicated by recent literature suggesting that gluten is not the only food component that may trigger symptoms experienced by this group of patients. The term 'non-coeliac wheat sensitivity' has been proposed as a more accurate term, allowing inclusion of other non-gluten wheat components such as fructans and amylase-trypsin inhibitors. There is inconsistent evidence when evaluating the effects of a gluten challenge in patients with suspected NCGS and there is a need for a standardised procedure to confirm the diagnosis, ultimately enabling the optimisation of clinical care. The present review will give an overview of the different gluten-related disorders and discuss the most recent scientific evidence investigating NCGS.

Leishmania (Mundinia) orientalis n. sp. (Trypanosomatidae), a parasite from Thailand responsible for localised cutaneous leishmaniasis

BackgroundLeishmaniasis is an emerging disease in Thailand with an unknown incidence or prevalence. Although the number of properly characterized and clinically confirmed cases is about 20, it is suspected that this low number masks a potentially high prevalence, with clinical disease typically manifesting itself against an immunocompromised background, but with a substantial number of subclinical or cured cases of infection. To date leishmaniasis in Thailand has been mainly ascribed to two taxa within the recently erected subgenus Mundinia Shaw, Camargo & Teixeira, 2016, Leishmania (Mundinia) martiniquensis Desbois, Pratlong & Dedet, 2014 and a species that has not been formally described prior to this study.ResultsA case of simple cutaneous leishmaniasis was diagnosed in a patient from Nan Province, Thailand. Molecular analysis of parasites derived from a biopsy sample revealed this to be a new species of Leishmania Ross, 1908, which has been named as Leishmania (Mundinia) orientalis Bates & Jariyapan n. sp. A formal description is provided, and this new taxon supercedes some isolates from the invalid taxon “Leishmania siamensis”. A summary of all known cases of leishmaniasis with a corrected species identification is provided.ConclusionsThree species of parasites are now known to cause leishmaniasis is Thailand, L. martiniquensis and L. orientalis n. sp. in the subgenus Mundinia, which contains the type-species Leishmania enriettii Muniz & Medina, 1948, and a single case of Leishmania infantum Nicolle, 1908. This study now enables epidemiological and other investigations into the biology of these unusual parasites to be conducted. It is recommended that the use of the taxonomically invalid name “L. siamensis” should be discontinued.

Non-celiac gluten/wheat sensitivity (NCGS)-acurrently undefined disorder without validated diagnostic criteria and of unknown prevalence: Position statement of the task force on food allergy of the German Society of Allergology and Clinical Immunology (DGAKI).

Within the last decade, non-celiac gluten/wheat sensitivity (NCGS) has been increasingly discussed not only in the media but also among medical specialties. The existence and the possible triggers of NCGS are controversial. Three international expert meetings which proposed recommendations for NCGS were not independently organized and only partially transparent regarding potential conflicts of interest of the participants. The present position statement reflects the following aspects about NCGS from an allergist’s and nutritionist’s point of view: (A) Validated diagnostic criteria and/or reliable biomarkers are still required. Currently, this condition is frequently self-diagnosed, of unknown prevalence and non-validated etiology. (B) Gluten has not been reliably identified as an elicitor of NCGS because of high nocebo and placebo effects. Double-blind, placebo-controlled provocation tests are of limited value for the diagnosis of NCGS and should be performed in a modified manner (changed relation of placebo and active substance). (C) Several confounders hamper the assessment of subjective symptoms during gluten-reduced or gluten-free diets. Depending on the selection of food items, e.g., an increased vegetable intake with soluble fibers, diets may induce physiological digestive effects and can modify gastrointestinal transit times independent from the avoidance of gluten. (D) A gluten-free diet is mandatory in celiac disease based on scientific evidence. However, a medically unjustified avoidance of gluten may bear potential disadvantages and risks. (E) Due to a lack of diagnostic criteria, a thorough differential diagnostic work-up is recommended when NCGS is suspected. This includes a careful patient history together with a food-intake and symptom diary, if necessary an allergy diagnostic workup and a reliable exclusion of celiac disease. We recommend such a structured procedure since a medically proven diagnosis is required before considering the avoidance of gluten.

Sequential prevalence estimation with pooling and continuous test outcomes.

Prevalence estimation is crucial for controlling the spread of infections and diseases and for planning of health care services. Prevalence estimation is typically conducted via pooled, or group, testing due to limited testing budgets. We study a sequential estimation procedure that uses continuous pool readings and considers the dilution effect of pooling so as to efficiently estimate an unknown prevalence rate. Embedded into the sequential estimation procedure is an optimization model that determines the optimal pooling design (number of pools and pool sizes) under a limited testing budget, considering the trade-off between testing cost and estimation accuracy. Our numerical study indicates that the proposed sequential estimation procedure outperforms single-stage procedures, or procedures that use binary test outcomes. Further, the sequential procedure provides robust prevalence estimates in cases where the initial estimate of the unknown prevalence rate is poor, or the assumed distribution of the biomarker load in infected subjects is inaccurate. Thus, when limited and unreliable information is available about the current status of, or biomarker dynamics related to, an infection, the sequential procedure becomes an attractive estimation strategy, due to its ability to mitigate the initial bias.

The effect of a controlled gluten challenge in a group of patients with suspected non-coeliac gluten sensitivity: A randomized, double-blind placebo-controlled challenge.

Non-coeliac gluten-sensitivity (NCGS) has been proposed as a new entity with unknown prevalence and mechanisms, and there is a need for a standardized procedure to confirm the diagnosis. The objective of this study was to characterize the response to an oral gluten-challenge in patients with a symptom-relief when following a gluten free-diet (GFD). Twenty patients (14F/6M, age range: 21-62years) with suspected NCGS, without coeliac disease and wheat-allergy, were included while on a gluten-free diet. All patients went through four periods of double-blinded provocation, two with gluten and two with placebo in randomized order. They consumed two muffins a day (11/0g gluten) for 4days, followed by a 3-day wash-out. Gastrointestinal symptoms were recorded with questionnaires at baseline and after each provocation. We also investigated whether patients were able to correctly identify periods with gluten-exposure. Collectively the whole group reported the most severe symptoms after placebo (P=.012). Four out of twenty patients correctly identified the two periods when they received gluten, hence were diagnosed with NCGS. The diagnosed-group tended to show higher symptom scores than the not-diagnosed group both at baseline, after gluten exposure and after placebo, but no clear difference was seen between provocation with gluten and placebo. The not-diagnosed group showed more severe symptoms with placebo than with gluten (P=.029). The present study showed that the majority of patients with suspected NCGS are not able to identify when challenged with gluten in a double-blind placebo-controlled food challenge, indicating that gluten is not the cause of their symptoms.

Unknown HIV Infection Prevalence and Associated Factors: Findings from A University Teaching Hospital in Tanzania

Background: Early detection and effective treatment with antiretroviral drugs would help preserve/improve the immune system, ameliorate quality of life of persons with HIV/AIDS and prevent unintentional spread of the virus. To that end provider initiated HIV counseling and testing (PIHCT) is recommended as standard of care for all patients attending health facilities in HIV endemic countries. This study aimed at determining the prevalence and factors associated with unknown HIV infection among medical admissions at Muhimbili National Hospital (MNH) as an indicator of PIHTC practice in Dares salaam, Tanzania. Methods: Patients newly hospitalized into MNH medical wards with unknown HIV sero-status were recruited in this hospital based cross sectional study. Patients were interviewed, examined, counseled and tested for HIV. CD4+ T lymphocytes count was determined for HIV positive and patients were followed up to determine in hospital outcome and duration of stay. Results: Of the 505 patients with unknown HIV status, 30 (5.9%) tested positive for HIV and all of them had visited another health facility before being referred to MNH compared to 78.5% among those who tested negative (p=0.004). More than two thirds (66.7%) of the newly diagnosed HIV patients had advanced disease. But, history of chronic diarrhea and/or severe weight loss, severe wasting (Slim disease) common features of AIDS in the 1980s were not apparent despite the late clinical presentation. Patients presenting with fever, oral ulcers, oral candidiasis, altered mental status, generalized lymphadenopathy were more likely to be diagnosed with HIV infection. Age of ≥50 years had a negative correlation towards a new diagnosis of HIV infection. Conclusion: Over 85% of medical patients referred to MNH did not know their HIV status. Newly diagnosed HIV sero-positive patients did not present with AIDS defining illnesses although over two thirds of them had advanced disease and in hospital mortality was high.

Estimation of minimal disease prevalence from population genomic data: Application to primary familial brain calcification.

Primary Familial Brain Calcification (PFBC) is a rare calcifying disorder of the brain with autosomal dominant inheritance, of unknown prevalence. Four causal genes have been identified so far: SLC20A2, PDGFB, PDGFRB, and XPR1, with pathogenic, probably pathogenic or missense variants of unknown significance found in 27.7% probands in the French PFBC series. Estimating PFBC prevalence from a clinical input is arduous due to a large diversity of symptoms and ages of onset and to incomplete clinical penetrance. Abnormal calcifications on CT scan can be used as a reliable diagnostic biomarker whatever the clinical status, but differential diagnoses should be ruled out including the challenging exclusion of common basal ganglia calcifications. Our primary aim was to estimate the minimal prevalence of PFBC due to a variant in one of the known genes. We extracted variants from the four known genes present in the gnomAD database gathering genomic data from 138,632 individuals. We interpreted all variants based on their predicted effect, their frequency, and previous studies on PFBC patients. Using the most conservative estimate, the minimal prevalence of PFBC related to a variant in one of the four known genes was 4.5 p. 10,000 (95%CI [3.4-5.5] p. 10,000). We then used variant detection rates in patients to extrapolate an overall minimal prevalence of PFBC to 2.1 p. 1,000 (95%CI [1.9-2.4] p. 1,000). The population-based genomic analysis indicates that PFBC is not an exceptionally rare disorder, still underestimated and underdiagnosed.

Genetic testing for Refsum disease

Abstract We reviewed the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for Refsum disease. The disease has autosomal recessive inheritance, unknown prevalence, and is caused by variations in PEX7 and PHYH genes. Clinical diagnosis is based on clinical findings, ophthalmological examination, electroretinography, optical coherence tomography and phytanic acid assay. The genetic test is useful for confirming diagnosis, for differential diagnosis, couple risk assessment and access to clinical trials.

Myocarditis: A Rare Complication of 5-ASA Therapy

Introduction: Mesalamine is an unconjugated 5-aminosalicylate (5-ASA) approved for the treatment of inflammatory bowel disease (IBD). Developed as an alternative to sulfasalazine the 5-ASA agents are well tolerated with a favorable safety profile, but concerning side effects include paradoxical colitis, pancreatitis, pneumonitis, and nephrotoxicity. We present the case of hypersensitivity myocarditis, an exceedingly rare complication of mesalamine therapy. Case Report: A 27-year-old male with recently diagnosed Crohn's disease well controlled on oral mesalamine started three weeks prior presented with two days of sharp chest pain improved with sitting upright. He was tachycardic and hypotensive despite IV fluid resuscitation. Initial labs revealed normal lactate, but elevated inflammatory markers, troponin I (0.92ng/mL), and BNP (3753pg/mL). EKG was without ischemic changes and echocardiogram showed reduced systolic function, EF 25-30% with biventricular dilation. He was admitted to the ICU, started on IV steroids, and mesalamine discontinued. Cardiac MRI demonstrated late enhancement of the subepicardial lateral wall consistent with myocarditis. Extensive infectious and rheumatologic workup was unremarkable and the patient rapidly improved without further intervention. The heart failure service recommended right heart catheterization with endomyocardial biopsy, however, the patient declined. The etiology was determined a hypersensitivity myocarditis secondary to recent mesalamine use. He was discharged on prednisone and continued to improve at outpatient follow up. Discussion: Myocarditis is an incredibly rare complication of 5-ASA therapy with unknown prevalence. Two years of mesalamine safety data in France identified three possible cases of myocarditis of 130 adverse events, but is otherwise limited to case reports. Deemed a hypersensitivity reaction, patients respond rapidly to withdrawal of agent and have immediate recurrence when re-challenged. It is dose independent occurring days to months after exposure and may be delayed by steroid use. Misdiagnosis is common as it mimics serositis, a known reactive extraintestinal manifestation of IBD mirroring intestinal activity. There is no definitive diagnosis, however, correlation with recent 5-ASA initiation and myocardial biopsy showing eosinophilic infiltration are highly suggestive. Fatalities are documented but early identification is crucial as patients will do well with cessation of medication.

Scrotoschisis: a case report

BackgroundScrotoschisis is a rare congenital anomaly of the scrotal wall with idiopathic etiology and unknown prevalence. This pathology is extremely rare. We report a new case and review the literature for relevant data.Case presentationA 3-day-old full-term baby boy of African ethnicity, who had a homebirth, with birth weight of 2.7 kg presented to our emergency department with exteriorization of left testis; after clinical examination and proper investigations the diagnosis was scrotoschisis. Surgical treatment was performed by primary closure with excellent follow-up. We reviewed the literature to elaborate on the etiology of this pathology and its management.ConclusionsScrotoschisis is a rare congenital anomaly affecting healthy babies. Early management is substantial. Further studies are recommended to learn more about the etiology and long-term results, including the effect on the fertility.

Charles Bonnet syndrome in a child with congenital glaucoma

Abstract Case report The case is presented of a 12 year-old boy with congenital glaucoma and low visual acuity diagnosed with Charles Bonnet syndrome. This consisted of the acute onset of complex, repetitive, persistent, and with visual hallucinations (people, brooms and coffeemakers) of self-limited evolution without treatment. The patient was diagnosed with congenital glaucoma at 3 years of age, and subjected to a trabeculectomy in right eye, and trabeculectomy and keratoplasty in his left eye. Discussion Charles Bonnet syndrome symptoms have been described in adults, but their presence in children is poorly reflected in literature, with unknown characteristics and prevalence.

An Adaptive Approach to Locating Mobile HIV Testing Services.

Public health agencies suggest targeting "hotspots" to identify individuals with undetected HIV infection. However, definitions of hotspots vary. Little is known about how best to target mobile HIV testing resources. We conducted a computer-based tournament to compare the yield of 4 algorithms for mobile HIV testing. Over 180 rounds of play, the algorithms selected 1 of 3 hypothetical zones, each with unknown prevalence of undiagnosed HIV, in which to conduct a fixed number of HIV tests. The algorithms were: 1) Thompson Sampling, an adaptive Bayesian search strategy; 2) Explore-then-Exploit, a strategy that initially draws comparable samples from all zones and then devotes all remaining rounds of play to HIV testing in whichever zone produced the highest observed yield; 3) Retrospection, a strategy using only base prevalence information; and; 4) Clairvoyance, a benchmarking strategy that employs perfect information about HIV prevalence in each zone. Over 250 tournament runs, Thompson Sampling outperformed Explore-then-Exploit 66% of the time, identifying 15% more cases. Thompson Sampling's superiority persisted in a variety of circumstances examined in the sensitivity analysis. Case detection rates using Thompson Sampling were, on average, within 90% of the benchmark established by Clairvoyance. Retrospection was consistently the poorest performer. We did not consider either selection bias (i.e., the correlation between infection status and the decision to obtain an HIV test) or the costs of relocation to another zone from one round of play to the next. Adaptive methods like Thompson Sampling for mobile HIV testing are practical and effective, and may have advantages over other commonly used strategies.

Discovering the Unexpected with the Utilization of NGS in Diagnostics of Non-syndromic Hearing Loss Disorders: The Family Case of ILDR1-Dependent Hearing Loss Disorder

Sensorineural hearing loss (SNHL) is a heterogeneous family of hearing disabilities with congenital (including genetic) as well as acquired etiology. Congenital SNHL of genetic etiology is further sub-divided into autosomal dominant, autosomal recessive and X-linked SNHL. More than 60 genes are involved in the etiology of autosomal recessive non-syndromic hearing loss (ARNSHL) commonly manifesting as heterogeneous pre-lingual profound to severe non-progressive clinical phenotype. ILDR1-dependent ARNSHL (DFNB42, OMIM: # 609646) is a very rare sub-type of hearing disability, with unknown prevalence, caused by function-damaging genetic variants in ILDR1 gene reported in families of Middle-Eastern origin. ILDR1 (Immunoglobulin-Like Domain-containing Receptor 1) is involved in the development of semicircular canal, tricellular tight junction and auditory hair cells. An apparently non-consanguineous family of European ancestry with two affected siblings with profound progressive hearing loss characterized in their infancy and successfully treated with cochlear implants (CI) is presented. Genetic analysis of common ARNSHL genetic causes in the population of origin was negative, thus the next-generation sequencing (NGS) and family segregation analysis to identify underlying causative genetic variant was performed. Unexpectedly and atypical for the population of origin a homozygous non-sense variant ILDR1 c.942C > A (p.Cys314Ter) inherited from both heterozygous parents was identified in both patients. Contrary to the commonly reported phenotype, indices of a progressive hearing loss and potential compensatory mechanism of vestibular function were revealed with the analysis of clinical data. The utilization of NGS was demonstrated as an invaluable tool for the detection of atypical rare variants in diagnostics of unidentified hearing loss disorders.