A patient with a novel homozygous missense mutation in FTO and concomitant nonsense mutation in CETP.

TitleA patient with a novel homozygous missense mutation in FTO and concomitant nonsense mutation in CETP.
Publication TypeJournal Article
Year of Publication2016
AuthorsÇağlayan, AO, Tuysuz, B, Coşkun, S, Quon, J, Harmancı, AS, Baranoski, JF, Baran, B, E Erson-Omay, Z, Henegariu, O, Mane, SM, Bilguvar, K, Yasuno, K, Günel, M
JournalJ Hum Genet
Date Published2016 May
KeywordsAlpha-Ketoglutarate-Dependent Dioxygenase FTO, Apoptosis, Biopsy, Child, Preschool, Cholesterol Ester Transfer Proteins, Computational Biology, Consanguinity, DNA Copy Number Variations, DNA Mutational Analysis, Exome, Female, Gene Expression, Gene Expression Profiling, Genetic Association Studies, Genotype, High-Throughput Nucleotide Sequencing, Homozygote, Humans, Mutation, Missense, Phenotype, Transcriptome

The fat mass and obesity associated (FTO) gene has previously been associated with a variety of diseases and conditions, notably obesity, acute coronary syndrome and metabolic syndrome. Reports describing mutations in FTO as well as in FTO animal models have further demonstrated a role for FTO in the development of the brain and other organs. Here, we describe a patient born of consanguineous union who presented with microcephaly, developmental delay, behavioral abnormalities, dysmorphic facial features, hypotonia and other various phenotypic abnormalities. Whole-exome sequencing revealed a novel homozygous missense mutation in FTO and a nonsense mutation in the cholesteryl ester transfer protein (CETP). Exome copy number variation analysis revealed no disease-causing large duplications or deletions within coding regions. Patient's, her parents' and non-related control' fibroblasts were analyzed for morphologic defects, abnormal proliferation, apoptosis and transcriptome profile. We have shown that FTO is located in the nucleus of cells from each tested sample. Western blot analysis demonstrated no changes in patient FTO. Quantitative (qPCR) analysis revealed slightly decreased levels of FTO expression in patient cells compared with controls. No morphological or proliferation differences between the patient and control fibroblasts were observed. There is still much to be learned about the molecular mechanisms by which mutations in FTO contribute to such severe phenotypes.

Alternate JournalJ. Hum. Genet.
PubMed ID26740239
PubMed Central IDPMC4880488
Grant ListU54 HG006504 / HG / NHGRI NIH HHS / United States
UL1 TR001863 / TR / NCATS NIH HHS / United States