Universität zu Köln

Dafsari, Hormos Salimi, Kawalia, Amit, Sprute, Rosanne ORCID: 0000-0003-2457-6437, Karakaya, Mert, Malenica, Anna, Herkenrath, Peter, Nuernberg, Peter, Motameny, Susanne, Thiele, Holger and Cirak, Sebahattin (2019). Novel mutations in SLC6A5 with benign course in hyperekplexia. Cold Spring Harb. Mol. Case Stud., 5 (6). COLD SPRING HARBOR: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. ISSN 2373-2873

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Abstract

Infants suffering from life-threatening apnea, stridor, cyanosis, and increased muscle tone may often be misdiagnosed with infantile seizures and inappropriately treated because of lack and delay in genetic diagnosis. Here, we report a patient with increased muscle tone after birth and hypertonic attacks with life-threatening apnea but no epileptiform patterns in EEG recordings. We identified novel compound heterozygous variants in SLC6A5 (NM_004211.4:c.[1429T> C];[1430delC]) by trio whole-exome sequencing, containing a base deletion inherited by the asymptomatic mother leading to a frameshift (c.1430delC, p.Ser477PhefsTer9) and a de novo base exchange leading to an amino acid change (c.1429T > C, p.Ser477Pro). To date, there are four known disease-associated genes for primary hyperekplexia, all of which are involved in the functioning of glycinergic synapses. SLC6A5 encodes the sodium- and chloride-dependent glycine transporter 2 (GlyT2), which recaptures glycine, a major inhibitory transmitter in the brainstem and spinal cord. The diagnosis altered the patient's medical care to his benefit because SLC6A5 mutations with rather benign courses of hyperekplexia may be spared of needless pharmacotherapy. Symptoms eventually decreased in frequency until about once in 2 mo at 2 yr age. We present the first report of halting hyperekplexia episodes by maternal soothing in multiple instances. We highlight the importance of clarifying the genetic diagnosis by rapid next-generation sequencing techniques in this group of infantile apneic attacks with hyperekplexia due to the broad differential diagnoses.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dafsari, Hormos Salimi UNSPECIFIED UNSPECIFIED UNSPECIFIED Kawalia, Amit UNSPECIFIED UNSPECIFIED UNSPECIFIED Sprute, Rosanne UNSPECIFIED orcid.org/0000-0003-2457-6437 UNSPECIFIED Karakaya, Mert UNSPECIFIED UNSPECIFIED UNSPECIFIED Malenica, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Herkenrath, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Motameny, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Cirak, Sebahattin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-125104
DOI:	10.1101/mcs.a004465
Journal or Publication Title:	Cold Spring Harb. Mol. Case Stud.
Volume:	5
Number:	6
Date:	2019
Publisher:	COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Place of Publication:	COLD SPRING HARBOR
ISSN:	2373-2873
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MULTIPLE SEQUENCE ALIGNMENT; INHIBITORY GLYCINE RECEPTOR; COPY-NUMBER VARIATION; TRANSPORTER GLYT2; EXPRESSION; GENE; CLONAZEPAM; SUBUNIT; CLONING; MUSCLE Multiple languages Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12510