Universität zu Köln

Sprute, Rosanne ORCID: 0000-0003-2457-6437, Ardicli, Didem, Oguz, Kader Karli, Malenica-Mandel, Anna, Daimagueler, Hulya-Sevcan, Koy, Anne, Coskun, Turgay, Wang, Haicui, Topcu, Meral and Cirak, Sebahattin (2019). Clinical outcomes of two patients with a novel pathogenic variant in ASNS: response to asparagine supplementation and review of the literature. Hum. Genom. Var., 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2054-345X

Full text not available from this repository.

Abstract

Asparagine synthetase deficiency (ASNSD, OMIM #615574) is a rare autosomal recessive neurometabolic inborn error that leads to severe cognitive impairment. It manifests with microcephaly, intractable seizures, and progressive cerebral atrophy. Currently, there is no established treatment for this condition. In our pediatric cohort, we discovered, by whole-exome sequencing in two siblings from Turkey, a novel homozygous missense mutation in asparagine synthetase at NM_133436.3 (ASNS_v001): c.1108C>T that results in an amino acid exchange p.(Leu370Phe), in the C-terminal domain. After identification of the metabolic defect, treatment with oral asparagine supplementation was attempted in both patients for 24 months. Asparagine supplementation was well tolerated, and no further disease progression was observed during treatment. One of our patients showed mild developmental progress with increased levels of attention and improved nonverbal communication. These results support our hypothesis that asparagine supplementation should be further investigated as a treatment option for ASNSD. We further reviewed all previously reported ASNSD cases with regard for their clinical phenotypes and brain imaging findings to provide an essential knowledge base for rapid diagnosis and future clinical studies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sprute, Rosanne UNSPECIFIED orcid.org/0000-0003-2457-6437 UNSPECIFIED Ardicli, Didem UNSPECIFIED UNSPECIFIED UNSPECIFIED Oguz, Kader Karli UNSPECIFIED UNSPECIFIED UNSPECIFIED Malenica-Mandel, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Daimagueler, Hulya-Sevcan UNSPECIFIED UNSPECIFIED UNSPECIFIED Koy, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Coskun, Turgay UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Haicui UNSPECIFIED UNSPECIFIED UNSPECIFIED Topcu, Meral UNSPECIFIED UNSPECIFIED UNSPECIFIED Cirak, Sebahattin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-147954
DOI:	10.1038/s41439-019-0055-9
Journal or Publication Title:	Hum. Genom. Var.
Volume:	6
Date:	2019
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2054-345X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SYNTHETASE DEFICIENCY; SIBLINGS; SAFETY Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14795