Izvorni znanstveni članak
https://doi.org/10.3325/cmj.2024.65.198
Spectrum of genetic variants in 306 patients with nonsyndromic hearing loss from Croatia
Ivona Sansović
; Department of Medical and Laboratory Genetics, Endocrinology and Diabetology, Children’s Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia
*
Ana-Maria Meašić
; Department of Medical and Laboratory Genetics, Endocrinology and Diabetology, Children’s Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia
Adriana Bobinec
; Department of Medical and Laboratory Genetics, Endocrinology and Diabetology, Children’s Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia
Leona Morožin Pohovski
; Department of Medical and Laboratory Genetics, Endocrinology and Diabetology, Children’s Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia
Ljubica Odak
; Department of Medical and Laboratory Genetics, Endocrinology and Diabetology, Children’s Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia
Katarina Vulin
; Department of Medical and Laboratory Genetics, Endocrinology and Diabetology, Children’s Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia
Bernarda Lozić
; Paediatric Diseases Department, University Hospital of Split, Split, Croatia
Mijana Kero
; Paediatric Diseases Department, University Hospital of Split, Split, Croatia
Sanda Huljev Frković
; Department of Pediatrics, University Hospital Centre Zagreb, University of Zagreb, School of Medicine, Zagreb, Croatia
Silvija Pušeljić
; Department of Pediatrics, University Hospital Center Osijek, Osijek, Croatia
* Dopisni autor.
Sažetak
Aim To determine the spectrum and frequency of diseasecausing variants in patients with non-syndromic hearing
loss (NSHL) and to investigate the diagnostic yield of the
applied genetic methods.
Methods The study enrolled 306 unrelated patients with
childhood-onset, mild-to-profound NSHL referred to Chil
-
dren’s Hospital Zagreb for genetic testing between March
2006 and October 2023. The GJB2 variants were analyzed
with the multiplex ligation-dependent probe amplifica
-
tion method and Sanger sequencing of the coding region
of the GJB2 gene. In 21 patients negative for GJB2 biallelic
variants, clinical exome sequencing (CES) was performed.
Results Among 234 disease-associated GJB2 alleles de
-
tected, 19 were clinically relevant, of which 18 were report
-
ed as pathogenic/likely pathogenic. The c.35delG variant
accounted for 73.5% of the mutated alleles. More than half
of the patients with biallelic GJB2 variants (64/110, 58.2%)
were 35delG homozygotes. Seventeen non-GJB2 variants
were found in 10 genes (TECTA, NOG, SLC26A4, PCDH15,
TMPRSS3, USH2A, GATA3, MYO15A, SOX10, COL2A1) in 11
participants, and 5 variants (in TECTA, NOG, PCDH15, and
SOX10) were novel (29.4%).
Conclusion We were able to elucidate the genetic cause
of hearing loss in 121 patients, with an overall diagnostic
rate of 39.5%. The c.35delG was the most common vari
-
ant. CES allowed us to diagnose almost half of the patients
with HL; to distinguish NSHL from the syndromic form of
HL in cases where the phenotype was unclear or where
symptoms were absent from an early age; and to discover
novel variants.
Ključne riječi
Hrčak ID:
331955
URI
Datum izdavanja:
16.6.2024.
Posjeta: 0 *