Authors:	Häuser, Friederike Rossmann, Heidi Adenaeuer, Anke Shrestha, Annette Marandiuc, Dana Paret, Claudia Faber, Jörg Lackner, Karl J. Lämmle, Bernhard Beck, Olaf
Title:	Hereditary spherocytosis : can next-generation sequencing of the five most frequently affected genes replace time-consuming functional investigations?
Online publication date:	15-Dec-2023
Year of first publication:	2023
Language:	english
Abstract:	Congenital defects of the erythrocyte membrane are common in northern Europe and all over the world. The resulting diseases, for example, hereditary spherocytosis (HS), are often underdiagnosed, partly due to their sometimes mild and asymptomatic courses. In addition to a broad clinical spectrum, this is also due to the occasionally complex diagnostics that are not available to every patient. To test whether next-generation sequencing (NGS) could replace time-consuming spherocytosis-specific functional tests, 22 consecutive patients with suspected red cell membranopathy underwent functional blood tests. We were able to identify the causative genetic defect in all patients with suspected HS who underwent genetic testing (n = 17). The sensitivity of the NGS approach, which tests five genes (ANK1 (gene product: ankyrin1), EPB42 (erythrocyte membrane protein band4.2), SLC4A1 (band3), SPTA1 (α-spectrin), and SPTB (β-spectrin)), was 100% (95% confidence interval: 81.5–100.0%). The major advantage of genetic testing in the paediatric setting is the small amount of blood required (<200 µL), and compared to functional assays, sample stability is not an issue. The combination of medical history, basic laboratory parameters, and an NGS panel with five genes is sufficient for diagnosis in most cases. Only in rare cases, a more comprehensive functional screening is required.
DDC:	500 Naturwissenschaften 500 Natural sciences and mathematics 570 Biowissenschaften 570 Life sciences 610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9760
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	International journal of molecular sciences 24 23
Pages or article number:	17021
Publisher:	Molecular Diversity Preservation International
Publisher place:	Basel
Issue date:	2023
ISSN:	1422-0067
Publisher DOI:	10.3390/ijms242317021
Appears in collections:	DFG-491381577-G