A recessive form of extreme macrocephaly and mild intellectual disability complements the spectrum of PTEN hamartoma tumour syndrome
Schwerd T, Khaled AV, Schürmann M, Chen H, Händel N, Reis A, Gillessen-Kaesbach G, Uhlig HH, Abou Jamra R (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
Abstract
PTEN hamartoma tumour syndrome (PHTS) is caused by heterozygous variants in PTEN and is characterised by tumour predisposition, macrocephaly, and cognition impairment. Bi-allelic loss of PTEN activity has not been reported so far and animal models suggest that bi-allelic loss of PTEN activity is embryonically lethal. Here, we report the identification of a novel homozygous variant in PTEN, NM_000314.4; c.545T>C; p.Leu182Ser, in two adolescent siblings with severe macrocephaly and mild intellectual disability. The variant is predicted to be damaging and is associated with significantly increased phospho-S6 downstream of PTEN. The absence of tumours in the two homozygous siblings as well as lack of symptoms of PHTS in the heterozygous carriers of the family suggest that this particular variant is functionally hypomorphic rather than deleterious.European Journal of Human Genetics advance online publication, 7 October 2015; doi:10.1038/ejhg.2015.209.
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APA:
Schwerd, T., Khaled, A.V., Schürmann, M., Chen, H., Händel, N., Reis, A.,... Abou Jamra, R. (2015). A recessive form of extreme macrocephaly and mild intellectual disability complements the spectrum of PTEN hamartoma tumour syndrome. European Journal of Human Genetics. https://doi.org/10.1038/ejhg.2015.209
MLA:
Schwerd, Tobias, et al. "A recessive form of extreme macrocephaly and mild intellectual disability complements the spectrum of PTEN hamartoma tumour syndrome." European Journal of Human Genetics (2015).
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