Whole exome sequencing identifies a novel variant in an apoptosis-inducing factor gene associated with X-linked recessive hearing loss in a Chinese family

We report on the genetic analysis of a Chinese family in which four male patients presented with postlingual progressive hearing loss, associated with distal muscle wasting and unsteady ataxic gait. Using whole exome sequencing, we identified a new pathogenic variant (c.1463C>T, p.Pro488Leu) in the AIFM1 gene, which encodes the apoptosis-inducing factor mitochondrion-associated 1 precursor. AIFM1 is involved in the mitochondrial respiratory chain and cellular caspase-independent apoptosis pathway and has been reported to cause multiple phenotypes including hearing loss. The p.Pro488Leu missense variant segregated with symptoms in the pedigree. It was not found in the dbSNP database, databases of genomes and SNPs in the Chinese population, in 74 patients with sporadic hearing loss, or in 108 normal individuals.We also verified that this AIFM1variant enhanced cell apoptosis rates compared in 293T cells transfected with wild-type AIFM1. Different variations of AIFM1 give rise to different phenotypes in patients, and this is the second reported family with a variant in the C-terminal domain of AIFM1 showing the phenotype of hearing loss and peripheral neuropathy.
Source: Genetics and Molecular Biology - Category: Genetics & Stem Cells Source Type: research

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Publication date: Available online 9 December 2019Source: Canadian Journal of DiabetesAuthor(s): Lingning Huang, Yongze Zhang, Yunmin Wang, Ximei Shen, Sunjie YanAbstractAimsInvestigate association between diabetic peripheral neuropathy (DPN)and above normal blood pressure in non-hypertensive patients with type 2 diabetes mellitus(T2DM). Compare the achievement of clinical target for DPN and non-DPN withT2DM .MethodsA retrospective survey was administered to 3810 patients with type 2 diabetes. Cases were grouped according to the Toronto Clinical Scoring System (TCSS): Non-DPN, Mild DPN, Moderate DPN and Severe DPN. 1835 pa...
Source: Canadian Journal of Diabetes - Category: Endocrinology Source Type: research
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Source: Life Sciences - Category: Biology Source Type: research
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Source: JAIDS Journal of Acquired Immune Deficiency Syndromes - Category: Infectious Diseases Tags: Clinical Science Source Type: research
CONCLUSION: Hypervitaminosis B6 remains a possible cause of peripheral neuropathy and it may be caused by self-administration of over-the-counter vitamin-containing drugs. PMID: 31796339 [PubMed - as supplied by publisher]
Source: Revue de Medecine Interne - Category: Internal Medicine Tags: Rev Med Interne Source Type: research
Conclusions Our findings can contribute to the development of breast cancer survivorship care plans by emphasizing posttreatment SM. Implications for Practice Future SM support intervention for BCSs after treatment should focus on training SM skills, enhancing the survivor-provider relationship, and building survivor self-confidence.
Source: Cancer Nursing - Category: Nursing Tags: ARTICLES Source Type: research
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Source: Journal of Integrative Medicine - Category: Complementary Medicine Source Type: research
Research indicates that neurosteroids are locally synthesized in the central nervous system and play an important modulatory role in nociception. While the neurosteroidogenic enzyme, cytochrome P450 side-chain cleavage enzyme (P450scc), is the initiating enzyme of steroidogenesis, P450scc has not been examined under the pathophysiological conditions associated with peripheral neuropathy. Thus, we investigated whether chronic constriction injury (CCI) of the sciatic nerve increases the expression of P450scc in the spinal cord and whether this increase modulates serine racemase (Srr) expression and D-serine production contri...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In conclusion, we show that NCS1–InsP3R1 interaction enhances intracellular Ca2+ signaling in cells and can be modulated by altering or occluding the hydrophobic pocket of NCS1. This improved understanding of the NCS1–InsP3R1 interaction may facilitate the development of management strategies for diseases resulting from aberrant NCS1 expression.
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Signal Transduction Source Type: research
Authors: Hus I, Mańko J, Jawniak D, Jurczyszyn A, Charliński G, Poniewierska-Jasak K, Usnarska-Zubkiewicz L, Sawicki M, Druzd-Sitek A, Świderska A, Kopińska A, Grząśko N, Raźny M, Wędłowska A, Perzyński A, Gałązka A, Dytfeld D, Kubicki T, Rodzaj M, Waszczuk-Gajda A, Drozd-Sokołowska J, Pogłódek B, Pasternak A, Długosz-Danecka M, Szymczyk A, Dmoszyńska A Abstract The present retrospective analysis evaluated the efficacy and safety of the VTD (bortezomib, thalidomide, dexamethasone) regimen in 205 newly-diagnosed patients with multiple myeloma (MM) eligible for high dose therapy and autologous ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Machado R, Pinto-Basto J, Negrão L Abstract CMT disease caused by NEFL gene mutations is rare. The mode of inheritance can be dominant or recessive and nerve conduction velocities can be normal, reduced (demyelinating) or presenting intermediate values. Two Portuguese adult related members in two successive generations were affected by peripheral neuropathy, one with a chronic ataxic peripheral neuropathy and the other with a classical Charcot-Marie-Tooth phenotype. An axonal sensorimotor peripheral neuropathy was described at neurophysiology. A missense heterozygous mutation, c.794A> G (p.Tyr265...
Source: Acta Myologica - Category: Neurology Tags: Acta Myol Source Type: research
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