Novel compound heterozygous mutations in TELO2 in a patient with severe expression of You-Hoover-Fong syndrome

Shahida Moosa; Janine Altmüller; T. Lyngbye; Rikke Christensen; Yun Li; Peter Nürnberg; Gökhan Yigit; Ida Vogel; Bernd Wollnik

doi:10.1002/mgg3.287

Novel compound heterozygous mutations in TELO2 in a patient with severe expression of You-Hoover-Fong syndrome

Shahida Moosa, Janine Altmüller, T. Lyngbye, Rikke Christensen, Yun Li, Peter Nürnberg, Gökhan Yigit, Ida Vogel, Bernd Wollnik

Department of Biomedicine - Research and Education, Bartholin Building

Research output: Contribution to book/anthology/report/proceeding › Book chapter › Research › peer-review

13 Citations (Scopus)

Abstract

Background: Very 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. 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 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. 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 TELO2 mutational spectrum.

Original language	English
Title of host publication	Molecular Genetics & Genomic Medicine
Number of pages	5
Volume	5
Publication date	Sept 2017
Pages	580-584
DOIs	https://doi.org/10.1002/mgg3.287
Publication status	Published - Sept 2017

Keywords

Novel mutations
TELO2
You-Hoover-Fong syndrome
syndromic ID

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title = "Novel compound heterozygous mutations in TELO2 in a patient with severe expression of You-Hoover-Fong syndrome",

abstract = "Background: Very 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. 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 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. 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 TELO2 mutational spectrum.",

keywords = "Novel mutations, TELO2, You-Hoover-Fong syndrome, syndromic ID",

author = "Shahida Moosa and Janine Altm{\"u}ller and T. Lyngbye and Rikke Christensen and Yun Li and Peter N{\"u}rnberg and G{\"o}khan Yigit and Ida Vogel and Bernd Wollnik",

year = "2017",

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doi = "10.1002/mgg3.287",

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T1 - Novel compound heterozygous mutations in TELO2 in a patient with severe expression of You-Hoover-Fong syndrome

AU - Moosa, Shahida

AU - Altmüller, Janine

AU - Lyngbye, T.

AU - Christensen, Rikke

AU - Li, Yun

AU - Nürnberg, Peter

AU - Yigit, Gökhan

AU - Vogel, Ida

AU - Wollnik, Bernd

PY - 2017/9

Y1 - 2017/9

N2 - Background: Very 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. 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 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. 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 TELO2 mutational spectrum.

AB - Background: Very 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. 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 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. 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 TELO2 mutational spectrum.

KW - Novel mutations

KW - TELO2

KW - You-Hoover-Fong syndrome

KW - syndromic ID

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U2 - 10.1002/mgg3.287

DO - 10.1002/mgg3.287

M3 - Book chapter

C2 - 28944240

VL - 5

SP - 580

EP - 584

BT - Molecular Genetics & Genomic Medicine

ER -

Novel compound heterozygous mutations in TELO2 in a patient with severe expression of You-Hoover-Fong syndrome

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