Literature Watch
Hospitalization costs of cystic fibrosis in the United States: a retrospective analysis.
Hospitalization costs of cystic fibrosis in the United States: a retrospective analysis.
Hosp Pract (1995). 2018 Aug 01;:
Authors: Vadagam P, Kamal KM
Abstract
Objective To determine patient, hospital, and clinical characteristics associated with the length of stay (LOS), total hospital charges, and total hospital costs in cystic fibrosis (CF). Methods Hospital discharge records with primary and secondary diagnoses of CF were identified from the 2012 Kids' Inpatient Database (KID) consisting of inpatient records of ages 0-20 years; and 2012 National Inpatient Sample (NIS) consisting of inpatient records of ages 21 and above. Both the databases are part of the Healthcare Cost and Utilization Project (HCUP). Patient demographics, hospital characteristics, clinical characteristics and outcome measures from KID and NIS were utilized in the analyses. Univariate and multivariate statistical analyses were conducted using IBM SPSS Statistics 24.0. Results A total of 3,142 and 10,258 CF-related hospital discharges were identified from 2012 KID and 2012 NIS databases, respectively. Among children, the mean (SD) LOS was 9.79 (10.51) days with a mean hospital costs of $26,249.23 (40,592.81). Adults had a mean LOS of 8.54 (8.42) days with a mean hospital costs of $21,600.91 (31,997.52). Number of procedures and total comorbidities were identified as the most important predictors of LOS, total hospital charges, and total hospital costs in both datasets. Conclusions Hospitalizations contribute significantly to the economic burden of CF. As inpatient costs in CF vary by patient, clinical, and hospital characteristics, healthcare decision makers need to utilize a targeted approach in different age groups to reduce hospital admission rates and the overall economic burden of CF.
PMID: 30067115 [PubMed - as supplied by publisher]
The pulmonary microbiome: challenges of a new paradigm.
The pulmonary microbiome: challenges of a new paradigm.
J Bras Pneumol. 2018 Jul 30;:0
Authors: Costa AN, Costa FMD, Campos SV, Salles RK, Athanazio RA
Abstract
The study of the human microbiome-and, more recently, that of the respiratory system-by means of sophisticated molecular biology techniques, has revealed the immense diversity of microbial colonization in humans, in human health, and in various diseases. Apparently, contrary to what has been believed, there can be nonpathogenic colonization of the lungs by microorganisms such as bacteria, fungi, and viruses. Although this physiological lung microbiome presents low colony density, it presents high diversity. However, some pathological conditions lead to a loss of that diversity, with increasing concentrations of some bacterial genera, to the detriment of others. Although we possess qualitative knowledge of the bacteria present in the lungs in different states of health or disease, that knowledge has advanced to an understanding of the interaction of this microbiota with the local and systemic immune systems, through which it modulates the immune response. Given this intrinsic relationship between the microbiota and the lungs, studies have put forth new concepts about the pathophysiological mechanisms of homeostasis in the respiratory system and the potential dysbiosis in some diseases, such as cystic fibrosis, COPD, asthma, and interstitial lung disease. This departure from the paradigm regarding knowledge of the lung microbiota has made it imperative to improve understanding of the role of the microbiome, in order to identify possible therapeutic targets and to develop innovative clinical approaches. Through this new leap of knowledge, the results of preliminary studies could translate to benefits for our patients.
PMID: 30066739 [PubMed - as supplied by publisher]
Two NAD-independent l-lactate dehydrogenases drive l-lactate utilization in Pseudomonas aeruginosa PAO1.
Two NAD-independent l-lactate dehydrogenases drive l-lactate utilization in Pseudomonas aeruginosa PAO1.
Environ Microbiol Rep. 2018 Aug 01;:
Authors: Wang Y, Xiao D, Liu Q, Zhang Y, Hu C, Sun J, Yang C, Xu P, Ma C, Gao C
Abstract
Pseudomonas aeruginosa often establishes a chronic infection in the airways of patients with cystic fibrosis (CF). l-Lactate is the most abundant carbon source in CF sputum, and l-lactate utilization may be important for P. aeruginosa to survive in the lungs of CF patients. In this study, the key enzymes involved in l-lactate utilization by P. aeruginosa PAO1 were characterized using synthetic CF sputum medium (SCFM). A highly conserved membrane-bound NAD-independent l-lactate dehydrogenase (l-iLDH) encoded by lldD (PA4771) and a novel flavin-containing membrane-bound l-iLDH encoded by lldA (PA2382) were both found to contribute to l-lactate utilization by P. aeruginosa PAO1, and an lldD and lldA double mutant was incapable of growing in a medium containing l-lactate as the sole carbon source. This study clarifies the mechanism and importance of l-lactate catabolism and demonstrates the first Pseudomonas spp. expressing two l-lactate-oxidizing enzymes. This article is protected by copyright. All rights reserved.
PMID: 30066495 [PubMed - as supplied by publisher]
Proteomic interaction profiling reveals KIFC1 as a factor involved in early targeting of F508del-CFTR to degradation.
Proteomic interaction profiling reveals KIFC1 as a factor involved in early targeting of F508del-CFTR to degradation.
Cell Mol Life Sci. 2018 Jul 31;:
Authors: Canato S, Santos JD, Carvalho AS, Aloria K, Amaral MD, Matthiesen R, Falcao AO, Farinha CM
Abstract
Misfolded F508del-CFTR, the main molecular cause of the recessive disorder cystic fibrosis, is recognized by the endoplasmic reticulum (ER) quality control (ERQC) resulting in its retention and early degradation. The ERQC mechanisms rely mainly on molecular chaperones and on sorting motifs, whose presence and exposure determine CFTR retention or exit through the secretory pathway. Arginine-framed tripeptides (AFTs) are ER retention motifs shown to modulate CFTR retention. However, the interactions and regulatory pathways involved in this process are still largely unknown. Here, we used proteomic interaction profiling and global bioinformatic analysis to identify factors that interact differentially with F508del-CFTR and F508del-CFTR without AFTs (F508del-4RK-CFTR) as putative regulators of this specific ERQC checkpoint. Using LC-MS/MS, we identified kinesin family member C1 (KIFC1) as a stronger interactor with F508del-CFTR versus F508del-4RK-CFTR. We further validated this interaction showing that decreasing KIFC1 levels or activity stabilizes the immature form of F508del-CFTR by reducing its degradation. We conclude that the current approach is able to identify novel putative therapeutic targets that can be ultimately used to the benefit of CF patients.
PMID: 30066085 [PubMed - as supplied by publisher]
Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
New Paradigms in Tissue Communication-from mediators to metabolic function (RC2 Clinical Trials Optional)
Notice of Information to the Specific Areas of Research Interest for PAR-16-021 "NHLBI TOPMed: Omics Phenotypes of Heart, Lung, and Blood Disorders (X01)"
"systems biology"; +31 new citations
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Chemical-induced disease extraction via recurrent piecewise convolutional neural networks.
Chemical-induced disease extraction via recurrent piecewise convolutional neural networks.
BMC Med Inform Decis Mak. 2018 Jul 23;18(Suppl 2):60
Authors: Li H, Yang M, Chen Q, Tang B, Wang X, Yan J
Abstract
BACKGROUND: Extracting relationships between chemicals and diseases from unstructured literature have attracted plenty of attention since the relationships are very useful for a large number of biomedical applications such as drug repositioning and pharmacovigilance. A number of machine learning methods have been proposed for chemical-induced disease (CID) extraction due to some publicly available annotated corpora. Most of them suffer from time-consuming feature engineering except deep learning methods. In this paper, we propose a novel document-level deep learning method, called recurrent piecewise convolutional neural networks (RPCNN), for CID extraction.
RESULTS: Experimental results on a benchmark dataset, the CDR (Chemical-induced Disease Relation) dataset of the BioCreative V challenge for CID extraction show that the highest precision, recall and F-score of our RPCNN-based CID extraction system are 65.24, 77.21 and 70.77%, which is competitive with other state-of-the-art systems.
CONCLUSIONS: A novel deep learning method is proposed for document-level CID extraction, where domain knowledge, piecewise strategy, attention mechanism, and multi-instance learning are combined together. The effectiveness of the method is proved by experiments conducted on a benchmark dataset.
PMID: 30066652 [PubMed - in process]
Drug Repurposing in Parkinson's Disease.
Drug Repurposing in Parkinson's Disease.
CNS Drugs. 2018 Jul 31;:
Authors: Athauda D, Foltynie T
Abstract
The development of an intervention to slow or halt disease progression remains the greatest unmet therapeutic need in Parkinson's disease. Given the number of failures of various novel interventions in disease-modifying clinical trials in combination with the ever-increasing costs and lengthy processes for drug development, attention is being turned to utilizing existing compounds approved for other indications as novel treatments in Parkinson's disease. Advances in rational and systemic drug repurposing have identified a number of drugs with potential benefits for Parkinson's disease pathology and offer a potentially quicker route to drug discovery. Here, we review the safety and potential efficacy of the most promising candidates repurposed as potential disease-modifying treatments for Parkinson's disease in the advanced stages of clinical testing.
PMID: 30066310 [PubMed - as supplied by publisher]
Variants of FasL and ABCC5 are predictive of outcome after chemotherapy-based treatment in osteosarcoma.
Variants of FasL and ABCC5 are predictive of outcome after chemotherapy-based treatment in osteosarcoma.
J Bone Oncol. 2018 Sep;12:44-48
Authors: Xu L, Xia C, Sun Q, Sheng F, Xiong J, Wang S
Abstract
Objectives: Previous pharmacogenetics studies showed that genetic variants could be indicative of the response to chemotherapy. We aimed to investigate whether variants of FasL, MSH2, ABCC5, CASP3 and CYP3A4 are associated with the outcome after chemotherapy-based treatment in osteosarcoma.
Methods: 132 osteosarcoma patients who had completed the neoadjuvant chemotherapy in our center were included. 5-year progression-free survival (PFS) was assessed from the initial treatment to the earliest sign of disease progression or death from any cause. 5 SNPs were genotyped using TaqMan SNP Genotyping Assay, including rs763110 of FasL, rs4638843 of MSH2, rs939338 of ABCC5, rs2720376 of CASP3 and rs4646437 of CYP3A4. Patients were classified into two groups according to the 5-year PFS (event/no event). The chi-square test was used to analyze difference of genotype frequency. Logistic regression analysis was used to determine the independent predictors of the PFS rate.
Results: The overall 5-year PFS was 61.4% (81/132). Genotype TT/CT of rs763110 and genotype GG/AG of rs939338 were significantly associated with the event of 5-year PFS (p = 0.028 for rs763110; p = 0.039 for rs939338). Patients with no risk allele showed a 5-year PFS of 73.7% (42/57), which was significantly higher than a PFS of 54.2% (26/48) for patients with one risk allele and 48.1% (13/27) for patients with two different risk alleles (p = 0.03). Logistic regression analysis showed that allele T of FasL rs763110 and allele G of ABCC5 rs939338 were independent risk factors of the 5-year PFS. The ORs were 2.14 (95%CI = 1.13-3.35, p = 0.01) for rs763110 and 1.73 (95%CI = 1.05-2.52, p = 0.03) for rs939338, respectively.
Conclusions: The association of variants of FASL and ABCC5 with survival outcome after chemotherapy was validated in patients with osteosarcoma. Our findings may provide a new insight into a more personalized treatment for patients with osteosarcoma.
PMID: 30065912 [PubMed]
Psychotherapy and Genetic Neuroscience: An Emerging Dialog.
Psychotherapy and Genetic Neuroscience: An Emerging Dialog.
Front Genet. 2018;9:257
Authors: Jiménez JP, Botto A, Herrera L, Leighton C, Rossi JL, Quevedo Y, Silva JR, Martínez F, Assar R, Salazar LA, Ortiz M, Ríos U, Barros P, Jaramillo K, Luyten P
Abstract
Recent research in psychiatric genetics has led to a move away from simple diathesis-stress models to more complex models of psychopathology incorporating a focus on gene-environment interactions and epigenetics. Our increased understanding of the way biology encodes the impact of life events on organisms has also generated more sophisticated theoretical models concerning the molecular processes at the interface between "nature" and "nurture." There is also increasing consensus that psychotherapy entails a specific type of learning in the context of an emotional relationship (i.e., the therapeutic relationship) that may also lead to epigenetic modifications across different therapeutic treatment modalities. This paper provides a systematic review of this emerging body of research. It is concluded that, although the evidence is still limited at this stage, extant research does indeed suggest that psychotherapy may be associated with epigenetic changes. Furthermore, it is argued that epigenetic studies may play a key role in the identification of biomarkers implicated in vulnerability for psychopathology, and thus may improve diagnosis and open up future research opportunities regarding the mechanism of action of psychotropic drugs as well as psychotherapy. We review evidence suggesting there may be important individual differences in susceptibility to environmental input, including psychotherapy. In addition, given that there is increasing evidence for the transgenerational transmission of epigenetic modifications in animals and humans exposed to trauma and adversity, epigenetic changes produced by psychotherapy may also potentially be passed on to the next generation, which opens up new perspective for prevention science. We conclude this paper stressing the limitations of current research and by proposing a set of recommendations for future research in this area.
PMID: 30065751 [PubMed]
A Genetic Score Associates With Pioglitazone Response in Patients With Non-alcoholic Steatohepatitis.
A Genetic Score Associates With Pioglitazone Response in Patients With Non-alcoholic Steatohepatitis.
Front Pharmacol. 2018;9:752
Authors: Kawaguchi-Suzuki M, Cusi K, Bril F, Gong Y, Langaee T, Frye RF
Abstract
Pioglitazone is used effectively to treat non-alcoholic steatohepatitis (NASH), but there is marked variability in response. This study examined whether genetic variation contributes to pioglitazone response variability in patients with NASH. This genetic substudy includes 55 participants of a randomized controlled trial designed to determine the efficacy of long-term pioglitazone treatment in patients with NASH. The primary outcome of the clinical trial was defined as ≥2-point reduction in the non-alcoholic fatty liver disease activity score (NAS). In this substudy, single nucleotide polymorphisms (SNPs) in putative candidate genes were tested for association with primary and secondary outcomes. A genetic response score was constructed based on the sum of response alleles for selected genes. The genetic response score was significantly associated with achievement of the primary outcome (odds ratio 1.74; 95% CI 1.27-2.54; p = 0.0015). ADORA1 rs903361 associated with resolution of NASH (p = 0.0005) and change in the ballooning score among Caucasian and Hispanic patients (p = 0.0005). LPL rs10099160 was significantly associated with change in ALT (p = 0.0005). The CYP2C8∗3 allele, which confers faster pioglitazone clearance in allele carriers, was associated with change in fibrosis score (p = 0.026). This study identified key genetic factors that explain some of the inter-individual variability in response to pioglitazone among patients with NASH.
PMID: 30065651 [PubMed]
Identification of Novel Protein Expression Changes Following Cisplatin Treatment and Application to Combination Therapy.
Identification of Novel Protein Expression Changes Following Cisplatin Treatment and Application to Combination Therapy.
J Proteome Res. 2017 Nov 03;16(11):4227-4236
Authors: Stark AL, Madian AG, Williams SW, Chen V, Wing C, Hause RJ, To LA, Gill AL, Myers JL, Gorsic LK, Ciaccio MF, White KP, Jones RB, Dolan ME
Abstract
Determining the effect of chemotherapeutic treatment on changes in protein expression can provide important targets for overcoming resistance. Due to challenges in simultaneously measuring large numbers of proteins, a paucity of data exists on global changes. To overcome these challenges, we utilized microwestern arrays that allowed us to measure the abundance and modification state of hundreds of cell signaling and transcription factor proteins in cells following drug exposure. HapMap lymphoblastoid cell lines (LCLs) were exposed to cisplatin, a chemotherapeutic agent commonly used to treat testicular, head and neck, non-small cell lung, and gynecological cancers. We evaluated the expression of 259 proteins following 2, 6, and 12 h of cisplatin treatment in two LCLs with discordant sensitivity to cisplatin. Of these 259 proteins, 66 displayed significantly different protein expression changes (p < 0.05). Fifteen of these proteins were evaluated in a second pair of LCLs with discordant sensitivities to cisplatin; six demonstrated significant differences in expression. We then evaluated a subset of 63 proteins in a second set of LCLs with discordant sensitivity, and 40% of those that were significant in the first pair were also significant in the second part with concordant directionality (p < 0.05). We functionally validated one of the top proteins identified, PDK1, and demonstrated a synergistic relationship between cisplatin and a PDK1 inhibitor in multiple lung cancer lines. This study highlights the potential for identifying novel targets through an understanding of cellular changes in protein expression and modification following drug treatments.
PMID: 28902521 [PubMed - indexed for MEDLINE]
Feed My Heart or Eat It: miR-22 Decides.
Feed My Heart or Eat It: miR-22 Decides.
J Am Coll Cardiol. 2016 10 04;68(14):1572-4
Authors: Matkovich SJ, Dorn GW
PMID: 27687199 [PubMed - indexed for MEDLINE]
Reply to: "miR-122 expression is not regulated during activation of hepatic stellate cells".
Reply to: "miR-122 expression is not regulated during activation of hepatic stellate cells".
J Hepatol. 2016 10;65(4):868
Authors: Li J, Li S
PMID: 27388922 [PubMed - indexed for MEDLINE]
Medical Genetics Summaries
Medical Genetics Summaries
Book. 2012
Authors: Pratt V, McLeod H, Rubinstein W, Dean L, Malheiro A
Abstract
Carvedilol (brand name Coreg) is used to treat heart failure and high blood pressure (hypertension). It is also used in patients who developed left ventricular dysfunction after having a heart attack (myocardial infarction, MI). In patients with cardiovascular disease, carvedilol is associated with improvements in quality of life, hospitalization rates, and survival. Carvedilol is a non-selective beta blocker (beta 1 and beta 2) and an alpha 1 blocker. It reduces the energy demands on the heart by blocking cardiac beta receptors, which decreases the heart rate and the force of heart contractions. Carvedilol lowers blood pressure by blocking alpha receptors on blood vessels, which relaxes and dilates blood vessels. CYP2D6 is one of the primary enzymes involved in activating and metabolizing carvedilol. Approximately 8% of Caucasians and 2% of most other populations have absent CYP2D6 activity and are predicted to be “CYP2D6 poor metabolizers.” The FDA-approved drug label for carvedilol states that plasma concentrations of carvedilol may be higher in CYP2D6 poor metabolizers compared to normal metabolizers, but does not discuss altering carvedilol dosing based on a patient’s CYP2D6 genotype (1). However, the label does state the dose of carvedilol should be individualized, and the dose should be monitored as it is gradually increased (up-titrated), based on tolerability and clinical response (Table 1). The Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP) recommend that no action is needed for carvedilol and CYP2D6 genotype. For CYP2D6 poor metabolizers, DPWG states that the plasma concentration of carvedilol can be elevated, but this does not result in an increase in side effects (Table 2) (2).
PMID: 30067327
Familial non-syndromic macular pseudocoloboma secondary to homozygous CLDN19 mutation.
Familial non-syndromic macular pseudocoloboma secondary to homozygous CLDN19 mutation.
Ophthalmic Genet. 2018 Aug 01;:1-7
Authors: Khan AO, Patel N, Ghazi NG, Alzahrani SS, Arold ST, Alkuraya FS
Abstract
PURPOSE: The purpose of this study is to uncover the genetic cause for non-syndromic macular "coloboma" (pseudocoloboma) in three brothers from a consanguineous family.
METHODS: Homozygosity mapping for the three affected brothers and whole-exome sequencing in one affected brother, followed by confirmatory Sanger sequencing and segregation analysis of the candidate gene for all immediate family members; molecular modeling of the candidate mutation; and review of clinical, imaging, and laboratory findings.
RESULTS: Three otherwise-healthy brothers (age 10, 10, and 6 years) had macular pseudocoloboma. Both parents and the fourth brother were not affected. Parents were first cousins. A novel homozygous missense variant in claudin 19 (CLND19: NM_148960.2:c. 263T>A; p.Val88Glu) segregated with the phenotype, and molecular modeling predicts an unfavorable effect to protein function. All prior reported biallelic CLND19 mutations cause symptomatic hypomagnesemia with hypercalciuria and nephrocalcinosis, often with concurrent macular pseudocoloboma. However, general physical assessment, metabolic profile, and renal imaging for the three affected brothers were normal.
CONCLUSIONS: A homozygous CLDN19 mutation can cause macular pseudocoloboma without evidence for systemic disease in children. This is the first reported family with CLDN19 mutations to have an ocular phenotype only; however, those identified to harbor biallelic CLDN19 mutations should be considered at risk for the extraocular manifestations that have previously been associated with mutations in the gene.
PMID: 30067419 [PubMed - as supplied by publisher]
Exploring the Clinical and Genetic Spectrum of Steroid Resistant Nephrotic Syndrome: The PodoNet Registry.
Exploring the Clinical and Genetic Spectrum of Steroid Resistant Nephrotic Syndrome: The PodoNet Registry.
Front Pediatr. 2018;6:200
Authors: Trautmann A, Lipska-Ziętkiewicz BS, Schaefer F
Abstract
Background: Steroid resistant nephrotic syndrome (SRNS) is a rare condition, accounting for 10-15% of all children with idiopathic nephrotic syndrome. SRNS can be caused by genetic abnormalities or immune system dysfunction. The prognosis of SRNS varies from permanent remission to progression to end-stage kidney disease, and post-transplant recurrence is common. Objectives: The PodoNet registry project aims to explore the demographics and phenotypes of immune-mediated and genetic forms of childhood SRNS, to assess genotype-phenotype correlations, to evaluate clinical management and long-term outcomes, and to search for novel genetic entities and diagnostic and prognostic biomarkers in SRNS. Methods: In 2009, an international registry for SRNS was established to collect retro- and prospective information on renal and extrarenal disease manifestations, histopathological and genetic findings and information on family history, pharmacotherapy responsiveness and long-term outcomes. To date, more than 2,000 patients have been enrolled at 72 pediatric nephrology centers, constituting the largest pediatric SRNS cohort assembled to date. Results: In the course of the project, traditional Sanger sequencing was replaced by NGS-based gene panel screening covering over 30 podocyte-related genes complemented by whole exome sequencing. These approaches allowed to establish genetic diagnoses in 24% of the patients screened, widened the spectrum of genetic disease entities presenting with SRNS phenotype (COL4A3-5, CLCN5), and contributed to the discovery of new disease causing genes (MYOE1, PTPRO). Forty two percent of patients responded to intensified immunosuppression with complete or partial remission of proteinuria, whereas 58% turned out multi-drug resistant. Medication responsiveness was highly predictive of a favorable long-term outcome, whereas the diagnosis of genetic disease was associated with a high risk to develop end-stage renal disease during childhood. Genetic SRNS forms were generally resistant to immunosuppressive treatment, justifying to avoid such pharmacotherapies altogether once a genetic diagnosis is established. Even symptomatic anti-proteinuric treatment with RAS antagonists seems to be challenging and of limited efficacy in genetic forms of SRNS. The risk of post-transplant disease recurrence was around 30% in non-genetic SRNS whereas it is negligible in genetic cases. Conclusion: In summary, the PodoNet Registry has collected detailed clinical and genetic information in a large SRNS cohort and continues to generate fundamental insights regarding demographic and etiological disease aspects, genotype-phenotype associations, the efficacy of therapeutic strategies, and long-term patient and renal outcomes including post-transplant disease recurrence.
PMID: 30065916 [PubMed]
An OTOF Frameshift Variant Associated with Auditory Neuropathy Spectrum Disorder.
An OTOF Frameshift Variant Associated with Auditory Neuropathy Spectrum Disorder.
Curr Genomics. 2018 Aug;19(5):370-374
Authors: Xia H, Huang X, Xu H, Guo Y, Hu P, Deng X, Yang Z, Liu A, Deng H
Abstract
Background: Auditory Neuropathy Spectrum Disorder (ANSD) is manifested as impairment of auditory nerve activity but preservation of the outer hair cell function.
Objective: This study was to detect the disease-causing gene and variant(s) in a Chinese ANSD family.
Methods: A four-generation consanguineous Chinese ANSD family and 200 unrelated healthy controls were enrolled. Exome sequencing and Sanger sequencing were applied to identify the genetic basis for ANSD in this family.
Results: Exome sequencing detected a c.1236delC variant of the otoferlin gene in an apparently homozygous state. Sanger sequencing confirmed that the variant co-segregating with the phenotype of hearing impairments in this family. The variant was not detected in 200 healthy controls. The c.1236delC alteration may result in a truncated otoferlin missing the C2C-C2F domains and the C-terminal transmembrane domain, and thus severely damages Ca2+-dependent synaptic vesicle fusion and targeting function of the otoferlin.
Conclusion: Our study suggested that the c.1236delC alteration in the otoferlin gene may be the disease-causing variant in this family, and also shed new light on genetic counseling to this ANSD family.
PMID: 30065612 [PubMed]
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