Open AccessNovel compound heterozygous mutations in TELO 2 in a patient with severe expression of You‐Hoover‐Fong syndrome
Author(s) -
Moosa Shahida,
Altmüller Janine,
Lyngbye Troels,
Christensen Rikke,
Li Yun,
Nürnberg Peter,
Yigit Gökhan,
Vogel Ida,
Wollnik Bernd
Publication year - 2017
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.287
Subject(s) - global developmental delay , microcephaly , compound heterozygosity , exome sequencing , medicine , intellectual disability , loss function , retinitis pigmentosa , genetics , missense mutation , exome , hearing loss , bioinformatics , pediatrics , biology , mutation , audiology , phenotype , gene
Background Very recently, compound heterozygous loss‐of‐function mutations in TELO 2 were shown to underlie the newly‐described You‐Hoover‐Fong syndrome. TELO 2 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 ( PIKK s). Patients with mutations in TELO 2 present with microcephaly and associated intellectual disability, postnatal growth retardation and dysmorphic features. Here, we describe Danish sisters with two novel mutations in TELO 2 . 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 . Methods The 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. Results Two novel, compound heterozygous mutations in TELO 2 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. Conclusion This 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 TELO 2 mutational spectrum.