Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Kim, Nayoung K.D.; Kim, Ah Reum; Park, Kyung Tae; Kim, So Young; Kim, Min Young; Nam, Jae Yong; Woo, Se Jun; Oh, Seung Ha; Park, Woong-Yang; Choi, Byung Yoon

doi:10.1038/gim.2014.213

Cited by 48 publications

(55 citation statements)

References 37 publications

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“…Although for the majority of this group the de novo mutation represented a single dominant hit causative of the phenotype, in one case the de novo mutation was in fact the second hit in an autosomal recessive form of retinitis pigmentosa. Similarly, in a cohort suffering from mild-to-moderate sensorineural hearing loss, de novo mutations were identified in two out of eleven sporadic cases [149], also suggesting a role for de novo mutations in this heterogeneous disorder.…”

Section: De Novo Mutations In Human Diseasementioning

confidence: 99%

New insights into the generation and role of de novo mutations in health and disease

2016

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Aside from inheriting half of the genome of each of our parents, we are born with a small number of novel mutations that occurred during gametogenesis and postzygotically. Recent genome and exome sequencing studies of parent–offspring trios have provided the first insights into the number and distribution of these de novo mutations in health and disease, pointing to risk factors that increase their number in the offspring. De novo mutations have been shown to be a major cause of severe early-onset genetic disorders such as intellectual disability, autism spectrum disorder, and other developmental diseases. In fact, the occurrence of novel mutations in each generation explains why these reproductively lethal disorders continue to occur in our population. Recent studies have also shown that de novo mutations are predominantly of paternal origin and that their number increases with advanced paternal age. Here, we review the recent literature on de novo mutations, covering their detection, biological characterization, and medical impact.

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Section: De Novo Mutations In Human Diseasementioning

confidence: 99%

New insights into the generation and role of de novo mutations in health and disease

2016

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“…Various techniques, such as whole exome sequencing and targeted exome sequencing (TES), have made it possible to screen candidate genes in an extremely high-throughput manner. 1 However, making a conclusive molecular diagnosis still requires time and rigorous effort in many cases, particularly in nonsyndromic cases with rare variants. Thus, we recently suggested the importance of phenotype-driven genetic testing focusing on candidate genes according to the clinical phenotypes of the affected subjects.…”

Section: Introductionmentioning

confidence: 99%

Unraveling of Enigmatic Hearing-Impaired GJB2 Single Heterozygotes by Massive Parallel Sequencing

Kim

et al. 2016

Medicine

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“…Severe-to-profound congenital or prelingual hearing loss results in the delay of language and behavioural development at an early age5. Therefore, early diagnosis of hearing loss should be mandatory in screening procedures such as newborn hearing screening.…”

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confidence: 99%

“…Whole exome sequencing (WES) has also been successfully used for analysis of genetic factors for hearing loss514, Additionally, WES has facilitated the identification of novel genes associated with Mendelian disorders including hearing loss151617. Recent studies have identified several causative genes for NSHL, including GPSM2, DNMT1, ELMOD3, GRXCR2 , and ADCY1 , by WES1516181920.…”

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confidence: 99%

Genetic Predisposition to Sporadic Congenital Hearing Loss in a Pediatric Population

Jung

Lee

Cho

et al. 2017

Sci Rep

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Discriminating between inherited and non-inherited sporadic hearing loss is challenging. Here, we attempted to delineate genetic inheritance in simplex cases of severe-to-profound congenital hearing loss in Korean children. Variations in SLC26A4 and GJB2 in 28 children with bilateral severe-to-profound non-syndromic hearing loss (NSHL) without familial history were analyzed using Sanger sequencing. Genetic analysis of individuals without mutations in SLC26A4 and GJB2 was performed by whole exome sequencing (WES). Bi-allelic mutations in SLC26A4 and GJB2 were identified in 12 and 3 subjects, respectively. Of the 13 individuals without mutations in SLC26A4 and GJB2, 2 and 1 carried compound heterozygous mutations in MYO15A and CDH23, respectively. Thus, 64.3% (18/28) of individuals with NSHL were determined to be genetically predisposed. Individuals with sporadic severe-to-profound NSHL were found to mostly exhibit an autosomal recessive inheritance pattern. Novel causative candidate genes for NSHL were identified by analysis of WES data of 10 families without mutations in known causative genes. Bi-allelic mutations predisposing to NSHL were identified in 64.3% of subjects with sporadic severe-to-profound NSHL. Given that several causative genes for NSHL are still unidentified, genetic inheritance of sporadic congenital hearing loss could be more common than that indicated by our results.

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Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Cited by 48 publications

References 37 publications

New insights into the generation and role of de novo mutations in health and disease

New insights into the generation and role of de novo mutations in health and disease

Unraveling of Enigmatic Hearing-Impaired GJB2 Single Heterozygotes by Massive Parallel Sequencing

Genetic Predisposition to Sporadic Congenital Hearing Loss in a Pediatric Population

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