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Your search keyword '"Yntema, H. G."' showing total 2 results
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2 results on '"Yntema, H. G."'

1. Exploring the missing heritability in subjects with hearing loss, enlarged vestibular aqueducts, and a single or no pathogenic SLC26A4 variant

Author

Smits, J. J. (Jeroen J.), de Bruijn, S. E. (Suzanne E.), Lanting, C. P. (Cornelis P.), Oostrik, J. (Jaap), O’Gorman, L. (Luke), Mantere, T. (Tuomo), D. C. (DOOFNL Consortium), Cremers, F. P. (Frans P. M.), Roosing, S. (Susanne), Yntema, H. G. (Helger G.), de Vrieze, E. (Erik), Derks, R. (Ronny), Hoischen, A. (Alexander), Pegge, S. A. (Sjoert A. H.), Neveling, K. (Kornelia), Pennings, R. J. (Ronald J. E.), Kremer, H. (Hannie), Smits, J. J. (Jeroen J.), de Bruijn, S. E. (Suzanne E.), Lanting, C. P. (Cornelis P.), Oostrik, J. (Jaap), O’Gorman, L. (Luke), Mantere, T. (Tuomo), D. C. (DOOFNL Consortium), Cremers, F. P. (Frans P. M.), Roosing, S. (Susanne), Yntema, H. G. (Helger G.), de Vrieze, E. (Erik), Derks, R. (Ronny), Hoischen, A. (Alexander), Pegge, S. A. (Sjoert A. H.), Neveling, K. (Kornelia), Pennings, R. J. (Ronald J. E.), and Kremer, H. (Hannie)

Abstract

Pathogenic variants in SLC26A4 have been associated with autosomal recessive hearing loss (arHL) and a unilateral or bilateral enlarged vestibular aqueduct (EVA). SLC26A4 is the second most frequently mutated gene in arHL. Despite the strong genotype–phenotype correlation, a significant part of cases remains genetically unresolved. In this study, we investigated a cohort of 28 Dutch index cases diagnosed with HL in combination with an EVA but without (M0) or with a single (M1) pathogenic variant in SLC26A4. To explore the missing heritability, we first determined the presence of the previously described EVA-associated haplotype (Caucasian EVA (CEVA)), characterized by 12 single nucleotide variants located upstream of SLC26A4. We found this haplotype and a delimited V1-CEVA haplotype to be significantly enriched in our M1 patient cohort (10/16 cases). The CEVA haplotype was also present in two M0 cases (2/12). Short- and long-read whole genome sequencing and optical genome mapping could not prioritize any of the variants present within the CEVA haplotype as the likely pathogenic defect. Short-read whole-genome sequencing of the six M1 cases without this haplotype and the two M0/CEVA cases only revealed previously overlooked or misinterpreted splice-altering SLC26A4 variants in two cases, who are now genetically explained. No deep-intronic or structural variants were identified in any of the M1 subjects. With this study, we have provided important insights that will pave the way for elucidating the missing heritability in M0 and M1 SLC26A4 cases. For pinpointing the pathogenic effect of the CEVA haplotype, additional analyses are required addressing defect(s) at the RNA, protein, or epigenetic level.

Published
2021

2. The etiological evaluation of sensorineural hearing loss in children.

Author

van Beeck Calkoen, E. A., Engel, M. S. D., van de Kamp, J. M., Yntema, H. G., Goverts, S.T., Mulder, M.F., Merkus, P., and Hensen, E. F.

Subjects
SENSORINEURAL hearing loss, TEMPORAL bone, CONGENITAL disorders, ETIOLOGY of diseases, CHILDREN, HEARING disorder diagnosis, DIAGNOSIS of deafness, AUDIOMETRY, COMPUTED tomography, DEAFNESS, HEARING disorders, MAGNETIC resonance imaging, GENETIC markers, GENETIC testing, RETROSPECTIVE studies, SEVERITY of illness index
Abstract

This study aims to evaluate the etiology of pediatric sensorineural hearing loss (SNHL). A total of 423 children with SNHL were evaluated, with the focus on the determination of causative genetic and acquired etiologies of uni- and bilateral SNHL in relation to age at diagnosis and severity of the hearing loss. We found that a stepwise diagnostic approach comprising of imaging, genetic, and/or pediatric evaluation identified a cause for SNHL in 67% of the children. The most common causative finding in children with bilateral SNHL was causative gene variants (26%), and in children with unilateral SNHL, a structural anomaly of the temporal bone (27%). The probability of finding an etiologic diagnosis is significantly higher in children under the age of 1 year and children with profound SNHL.Conclusions: With our stepwise diagnostic approach, we found a diagnostic yield of 67%. Bilateral SNHL often has a genetic cause, whereas in unilateral SNHL structural abnormalities of the labyrinth are the dominant etiologic factor. The diagnostic yield is associated with the age at detection and severity of hearing loss: the highest proportion of causative abnormalities is found in children with a young age at detection or a profound hearing loss. What is Known: • Congenital sensorineural hearing loss is one of the most common congenital disorders • Determination of the cause is important for adequate management and prognosis and may include radiology, serology, and DNA analysis What is New: • Using a stepwise diagnostic approach, causative abnormalities are found in 67% both in uni- and bilateral SNHL, with the highest diagnostic yield in very young children and those suffering from profound hearing loss • Bilateral SNHL often has a genetic cause, whereas in unilateral SNHL structural abnormalities of the labyrinth are the dominant etiologic factor. [ABSTRACT FROM AUTHOR]

Published
2019
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