Cargando…

Postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous SUOX variant causing isolated sulfite oxidase deficiency

Rapid whole-genome sequencing (rWGS) has shown that genetic diseases are a common cause of infant mortality in neonatal intensive care units. Dried blood spots collected for newborn screening allow investigation of causes of infant mortality that were not diagnosed during life. Here, we present a ne...

Descripción completa

Detalles Bibliográficos
Autores principales: Owen, Mallory J., Lenberg, Jerica, Feigenbaum, Annette, Gold, Jeffrey, Chau, Kevin, Bezares-Orin, Zaira, Ding, Yan, Chowdhury, Shimul, Kingsmore, Stephen F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208044/
https://www.ncbi.nlm.nih.gov/pubmed/34117075
http://dx.doi.org/10.1101/mcs.a006091
_version_ 1783708876726599680
author Owen, Mallory J.
Lenberg, Jerica
Feigenbaum, Annette
Gold, Jeffrey
Chau, Kevin
Bezares-Orin, Zaira
Ding, Yan
Chowdhury, Shimul
Kingsmore, Stephen F.
author_facet Owen, Mallory J.
Lenberg, Jerica
Feigenbaum, Annette
Gold, Jeffrey
Chau, Kevin
Bezares-Orin, Zaira
Ding, Yan
Chowdhury, Shimul
Kingsmore, Stephen F.
author_sort Owen, Mallory J.
collection PubMed
description Rapid whole-genome sequencing (rWGS) has shown that genetic diseases are a common cause of infant mortality in neonatal intensive care units. Dried blood spots collected for newborn screening allow investigation of causes of infant mortality that were not diagnosed during life. Here, we present a neonate who developed seizures and encephalopathy on the third day of life that was refractory to antiepileptic medications. The patient died on day of life 16 after progressive respiratory failure and sepsis. The parents had lost two prior children after similar presentations, neither of whom had a definitive diagnosis. Postmortem rWGS of a dried blood spot identified a pathogenic homozygous frameshift variant in the SUOX gene associated with isolated sulfite oxidase deficiency (c.1390_1391del, p.Leu464GlyfsTer10). This case highlights that early, accurate molecular diagnosis has the potential to influence prenatal counseling and guide management in rare, genetic disorders and has added importance in cases of a strong family history and risk factors such as consanguinity.
format Online
Article
Text
id pubmed-8208044
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-82080442021-06-30 Postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous SUOX variant causing isolated sulfite oxidase deficiency Owen, Mallory J. Lenberg, Jerica Feigenbaum, Annette Gold, Jeffrey Chau, Kevin Bezares-Orin, Zaira Ding, Yan Chowdhury, Shimul Kingsmore, Stephen F. Cold Spring Harb Mol Case Stud Research Report Rapid whole-genome sequencing (rWGS) has shown that genetic diseases are a common cause of infant mortality in neonatal intensive care units. Dried blood spots collected for newborn screening allow investigation of causes of infant mortality that were not diagnosed during life. Here, we present a neonate who developed seizures and encephalopathy on the third day of life that was refractory to antiepileptic medications. The patient died on day of life 16 after progressive respiratory failure and sepsis. The parents had lost two prior children after similar presentations, neither of whom had a definitive diagnosis. Postmortem rWGS of a dried blood spot identified a pathogenic homozygous frameshift variant in the SUOX gene associated with isolated sulfite oxidase deficiency (c.1390_1391del, p.Leu464GlyfsTer10). This case highlights that early, accurate molecular diagnosis has the potential to influence prenatal counseling and guide management in rare, genetic disorders and has added importance in cases of a strong family history and risk factors such as consanguinity. Cold Spring Harbor Laboratory Press 2021-06 /pmc/articles/PMC8208044/ /pubmed/34117075 http://dx.doi.org/10.1101/mcs.a006091 Text en © 2021 Owen et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.
spellingShingle Research Report
Owen, Mallory J.
Lenberg, Jerica
Feigenbaum, Annette
Gold, Jeffrey
Chau, Kevin
Bezares-Orin, Zaira
Ding, Yan
Chowdhury, Shimul
Kingsmore, Stephen F.
Postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous SUOX variant causing isolated sulfite oxidase deficiency
title Postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous SUOX variant causing isolated sulfite oxidase deficiency
title_full Postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous SUOX variant causing isolated sulfite oxidase deficiency
title_fullStr Postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous SUOX variant causing isolated sulfite oxidase deficiency
title_full_unstemmed Postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous SUOX variant causing isolated sulfite oxidase deficiency
title_short Postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous SUOX variant causing isolated sulfite oxidase deficiency
title_sort postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous suox variant causing isolated sulfite oxidase deficiency
topic Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208044/
https://www.ncbi.nlm.nih.gov/pubmed/34117075
http://dx.doi.org/10.1101/mcs.a006091
work_keys_str_mv AT owenmalloryj postmortemwholegenomesequencingonadriedbloodspotidentifiesanovelhomozygoussuoxvariantcausingisolatedsulfiteoxidasedeficiency
AT lenbergjerica postmortemwholegenomesequencingonadriedbloodspotidentifiesanovelhomozygoussuoxvariantcausingisolatedsulfiteoxidasedeficiency
AT feigenbaumannette postmortemwholegenomesequencingonadriedbloodspotidentifiesanovelhomozygoussuoxvariantcausingisolatedsulfiteoxidasedeficiency
AT goldjeffrey postmortemwholegenomesequencingonadriedbloodspotidentifiesanovelhomozygoussuoxvariantcausingisolatedsulfiteoxidasedeficiency
AT chaukevin postmortemwholegenomesequencingonadriedbloodspotidentifiesanovelhomozygoussuoxvariantcausingisolatedsulfiteoxidasedeficiency
AT bezaresorinzaira postmortemwholegenomesequencingonadriedbloodspotidentifiesanovelhomozygoussuoxvariantcausingisolatedsulfiteoxidasedeficiency
AT dingyan postmortemwholegenomesequencingonadriedbloodspotidentifiesanovelhomozygoussuoxvariantcausingisolatedsulfiteoxidasedeficiency
AT chowdhuryshimul postmortemwholegenomesequencingonadriedbloodspotidentifiesanovelhomozygoussuoxvariantcausingisolatedsulfiteoxidasedeficiency
AT kingsmorestephenf postmortemwholegenomesequencingonadriedbloodspotidentifiesanovelhomozygoussuoxvariantcausingisolatedsulfiteoxidasedeficiency