Universität zu Köln

Moosa, Shahida ORCID: 0000-0002-4463-3067, Altmueller, Janine, Lyngbye, Troels, Christensen, Rikke, Li, Yun, Nuernberg, Peter, Yigit, Goekhan, Vogel, Ida ORCID: 0000-0002-1125-0393 and Wollnik, Bernd (2017). Novel compound heterozygous mutations in TELO2 in a patient with severe expression of You-Hoover-Fong syndrome. Mol. Genet. Genom. Med., 5 (5). S. 580 - 585. HOBOKEN: WILEY. ISSN 2324-9269

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Abstract

BackgroundVery recently, compound heterozygous loss-of-function mutations in TELO2 were shown to underlie the newly-described You-Hoover-Fong syndrome. TELO2 forms part of the co-chaperone triple T complex (TTT complex), which plays an important role in the maturation and stabilization of the phosphatidylinositol 3-kinase-related protein kinases (PIKKs). Patients with mutations in TELO2 present with microcephaly and associated intellectual disability, postnatal growth retardation and dysmorphic features. Here, we describe Danish sisters with two novel mutations in TELO2. In particular, we highlight the clinical features of the 22-year index patient, which are more severe than the original patients described, thereby expanding the clinical spectrum of YHFS. MethodsThe index patient was clinically examined and subsequently exome sequencing on her DNA was performed using the NimbleGen SeqCap EZ Human Exome Library v2.0 enrichment kit on an Illumina HiSeq2000 sequencer. ResultsTwo novel, compound heterozygous mutations in TELO2 were identified in the index patient and her deceased older sister. Both have clinical features in keeping with the original YHFS patients, although the index patient seems to represent the severe end of the clinical spectrum with very marked prenatal onset growth retardation and microcephaly, severe global developmental delay and facial dysmorphic features. Additional clinical findings include eye anomalies (bilateral congenital cataracts, retinitis pigmentosa, convergent squint), bilateral conductive hearing loss, an abnormal kidney and seizures. ConclusionThis report of Danish siblings with YHFS serves to expand the presentation of this new syndrome to include features in keeping with a form of microcephalic primordial dwarfism on the severe end of the clinical spectrum, and adds two novel mutations to the TELO2 mutational spectrum.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Moosa, Shahida UNSPECIFIED orcid.org/0000-0002-4463-3067 UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Lyngbye, Troels UNSPECIFIED UNSPECIFIED UNSPECIFIED Christensen, Rikke UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Yun UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Yigit, Goekhan UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogel, Ida UNSPECIFIED orcid.org/0000-0002-1125-0393 UNSPECIFIED Wollnik, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-218723
DOI:	10.1002/mgg3.287
Journal or Publication Title:	Mol. Genet. Genom. Med.
Volume:	5
Number:	5
Page Range:	S. 580 - 585
Date:	2017
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2324-9269
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21872