Universität zu Köln

Bamborschke, Daniel, Oezdemir, Oezkan, Kreutzer, Mona, Motameny, Susanne, Thiele, Holger ORCID: 0000-0002-0169-998X, Kribs, Angela, Doetsch, Joerg, Altmueller, Janine, Nuernberg, Peter and Cirak, Sebahattin (2021). Ultra-rapid emergency genomic diagnosis of Donahue syndrome in a preterm infant within 17 hours. Am. J. Med. Genet. A, 185 (1). S. 90 - 97. HOBOKEN: WILEY. ISSN 1552-4833

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Abstract

Genetic diseases are a major cause of neonatal morbidity and mortality. The clinical differential diagnosis in severely ill neonates, especially in premature infants, is challenging. Next generation sequencing (NGS) diagnostics is a valuable tool, but the turnaround time is often too long to provide a diagnosis in the time needed for clinical guidance in newborn intensive care units (NICU). To minimize turnaround time, we developed an ultra-rapid whole genome sequencing pipeline and tested it in clinical practice. Our pilot case, was a preterm infant presenting with several crises of dehydration, hypoglycaemia and hyponatremia together with nephrocalcinosis and hypertrophic cardiomyopathy. Whole genome sequencing was performed using a paired-end 2x75bp protocol. Sequencing data were exported after 50 sequencing cycles for a first analysis. After run completion, the rapid-sequencing protocol, a second analysis of the 2 x 75 paired-end run was performed. Both analyses comprised read-mapping and SNP-/indel calling on an on-site Edico Genome DRAGEN server, followed by functional annotation and pathogenicity prediction using in-house scripts. After the first analysis within 17 h, the emergency ultra-rapid protocol identified twonovelcompound heterozygous variants in the insulin receptor gene (INSR), pathogenic variants in which cause Donohue Syndrome. The genetic diagnosis could be confirmed by detection of hyperinsulinism and patient care adjusted. Nonetheless, we decided to pursue RNA studies, proving the functional effect of thenovelsplice variant and reduced expression levels ofINSRin patients skin fibroblasts.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bamborschke, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Oezdemir, Oezkan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreutzer, Mona UNSPECIFIED UNSPECIFIED UNSPECIFIED Motameny, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED orcid.org/0000-0002-0169-998X UNSPECIFIED Kribs, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Cirak, Sebahattin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-315142
DOI:	10.1002/ajmg.a.61917
Journal or Publication Title:	Am. J. Med. Genet. A
Volume:	185
Number:	1
Page Range:	S. 90 - 97
Date:	2021
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1552-4833
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INSULIN-RECEPTOR; DONOHUE SYNDROME; MUTATION Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31514