Universität zu Köln

Karakaya, Mert, Heller, Raoul, Kunde, Volkmar, Zimmer, Klaus-Peter, Chao, Cho-Ming, Nuernberg, Peter and Cirak, Sebahattin (2016). Novel Mutations in the Nonselective Sodium Leak Channel (NALCN) Lead to Distal Arthrogryposis with Increased Muscle Tone. Neuropediatrics, 47 (4). S. 273 - 278. STUTTGART: GEORG THIEME VERLAG KG. ISSN 1439-1899

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Abstract

Distal arthrogryposis (DA) is a feature in genetically and clinically heterogeneous groups of disorders. Mostly myopathic and neurogenic defects have been described, but many patients remain without genetic diagnosis. We are elaborating on the clinical presentation of neonatal cases with DA who carry novel mutations in the nonselective sodium leak channel (NALCN). Two patients reported herein were remarkable for central hypertonicity in addition to DA. By trio-whole exome sequencing, two undescribed de novo mutations in NALCN were revealed. Both mutations (p.F317C and p.V595F) are located on pore-forming segments of NALCN. Dominant NALCN mutations in the pore-forming segments have been identified in similar patients, whereas recessive mutations outside the pore-forming segments result in different phenotypes. Our findings with central hypertonia broaden the phenotypic spectrum of de novo mutations in the pore-forming segments of NALCN. Recent findings of successful acetazolamide treatment in patients with channelopathies might point to potential therapies based on the ion channel similarities and the location of the mutation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Karakaya, Mert UNSPECIFIED UNSPECIFIED UNSPECIFIED Heller, Raoul UNSPECIFIED UNSPECIFIED UNSPECIFIED Kunde, Volkmar UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmer, Klaus-Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Chao, Cho-Ming UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Cirak, Sebahattin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-268446
DOI:	10.1055/s-0036-1584084
Journal or Publication Title:	Neuropediatrics
Volume:	47
Number:	4
Page Range:	S. 273 - 278
Date:	2016
Publisher:	GEORG THIEME VERLAG KG
Place of Publication:	STUTTGART
ISSN:	1439-1899
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HYPOTONIA; GENOTYPE; DELAY Multiple languages Clinical Neurology; Pediatrics Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26844