Syndromic Hearing Loss: A Brief Review of Common Presentations and Genetics

Gettelfinger, John D.; Dahl, John P.

doi:10.1055/s-0037-1617454

Cited by 46 publications

(49 citation statements)

References 106 publications

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“…Although more than ten genes can cause this disorder 5 , only four were responsible for Usher syndrome in this Brazilian sample. The overwhelming majority of patients had pathogenic variants in the USH2A and MYO7A genes (90% of Usher cases) 21 , 25 .…”

Section: Discussionmentioning

confidence: 99%

Relative frequency of inherited retinal dystrophies in Brazil

Motta

Martin

Filippelli-Silva

et al. 2018

Sci Rep

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Among the Brazilian population, the frequency rates of inherited retinal dystrophies and their causative genes are underreported. To increase the knowledge about these dystrophies in our population, we retrospectively studied the medical records of 1,246 Brazilian patients with hereditary retinopathies during 20 years of specialized outpatient clinic care. Of these patients, 559 had undergone at least one genetic test. In this cohort, the most prevalent dystrophies were non-syndromic retinitis pigmentosa (35%), Stargardt disease (21%), Leber congenital amaurosis (9%), and syndromic inherited retinal dystrophies (12%). Most patients had never undergone genetic testing (55%), and among the individuals with molecular test results, 28.4% had negative or inconclusive results compared to 71.6% with a conclusive molecular diagnosis. ABCA4 was the most frequent disease-causing gene, accounting for 20% of the positive cases. Pathogenic variants also occurred frequently in the CEP290, USH2A, CRB1, RPGR, and CHM genes. The relative frequency rates of different inherited retinal dystrophies in Brazil are similar to those found globally. Although mutations in more than 250 genes lead to hereditary retinopathies, only 66 genes were responsible for 70% of the cases, which indicated that smaller and cheaper gene panels can be just as effective and provide more affordable solutions for implementation by the Brazilian public health system.

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Section: Discussionmentioning

confidence: 99%

Relative frequency of inherited retinal dystrophies in Brazil

Motta

Martin

Filippelli-Silva

et al. 2018

Sci Rep

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“…Today, ∼466 million people have disabling HL (World Health Organization [WHO], March ), including 1 in 500 newborns (Morton & Nance, ), 34 million children, and one‐half of all individuals over the age of 75 (Yamasoba et al., ). HL can be one feature of a more complex clinical syndrome (Gettelfinger & Dahl, ). Isolated hearing loss, referred to as nonsyndromic autosomal recessive hearing loss (NSARHL), is also genetically heterogenous.…”

Section: Introductionmentioning

confidence: 99%

Global genetic insight contributed by consanguineous Pakistani families segregating hearing loss

Rlp

Faridi

et al. 2018

Human Mutation

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Consanguineous Pakistani pedigrees segregating deafness have contributed decisively to the discovery of 31 of the 68 genes associated with nonsyndromic autosomal recessive hearing loss (HL) worldwide. In this study, we utilized genome-wide genotyping, Sanger and exome sequencing to identify 163 DNA variants in 41 previously reported HL genes segregating in 321 Pakistani families. Of these, 71 (43.6%) variants identified in 29 genes are novel. As expected from genetic studies of disorders segregating in consanguineous families, the majority of affected individuals (94.4%) are homozygous for HL-associated variants, with the other variants being compound heterozygotes. The five most common HL genes in the Pakistani population are SLC26A4, MYO7A, GJB2, CIB2 and HGF, respectively. Our study provides a profile of the genetic etiology of HL in Pakistani families, which will allow for the development of more efficient genetic diagnostic tools, aid in accurate genetic counseling and guide application of future gene-based therapies. These findings are also valuable in interpreting pathogenicity of variants that are potentially associated with HL in individuals of all ancestries. The Pakistani population, and its infrastructure for studying human genetics, will continue to be valuable to gene discovery for HL and other inherited disorders.

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“…The last PBD under the Zellweger spectrum is infantile Refsum disease, where a build-up of phytanic acid and other very-long-chain fatty acids in the body (a result of mutated PEX genes) leads to neurological symptoms such as mixed neuropathy and hearing loss (Warren et al, 2018). Outside the Zellweger spectrum, adult Refsum disease has similar symptoms to infantile Refsum disease, but the adult-onset disease is due to a mutation in the PHYH gene that codes for the peroxisomal enzyme phytanoyl-CoA dioxygenase, which peroxisomes use to break down phytanic acid into pristanic acid (Wanders et al, 2011;Wanders and Poll-The, 2017;Gettelfinger and Dahl, 2018).…”

Section: Pexophagy In Mammalsmentioning

confidence: 99%

Peroxisomal Dysfunction in Neurological Diseases and Brain Aging

Uzor¹,

McCullough

Tsvetkov

2020

Front. Cell. Neurosci.

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Peroxisomes exist in most cells, where they participate in lipid metabolism, as well as scavenging the reactive oxygen species (ROS) that are produced as by-products of their metabolic functions. In certain tissues such as the liver and kidneys, peroxisomes have more specific roles, such as bile acid synthesis in the liver and steroidogenesis in the adrenal glands. In the brain, peroxisomes are critically involved in creating and maintaining the lipid content of cell membranes and the myelin sheath, highlighting their importance in the central nervous system (CNS). This review summarizes the peroxisomal lifecycle, then examines the literature that establishes a link between peroxisomal dysfunction, cellular aging, and age-related disorders that affect the CNS. This review also discusses the gap of knowledge in research on peroxisomes in the CNS.

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Syndromic Hearing Loss: A Brief Review of Common Presentations and Genetics

Cited by 46 publications

References 106 publications

Relative frequency of inherited retinal dystrophies in Brazil

Relative frequency of inherited retinal dystrophies in Brazil

Global genetic insight contributed by consanguineous Pakistani families segregating hearing loss

Peroxisomal Dysfunction in Neurological Diseases and Brain Aging

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