Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features

American Journal of Medical Genetics. Part a
Caleb P BuppAndré S Bachmann

Abstract

The ornithine decarboxylase 1 (ODC1) gene plays an important role in physiological and cell developmental processes including embryogenesis, organogenesis, and neoplastic cell growth. Here, we report an 32-month-old Caucasian female with a heterozygous de novo nonsense mutation in the ODC1 gene that leads to a premature abrogation of 14-aa residues at the ODC protein c-terminus. This is the first human case confirming similar symptoms observed in a transgenic ODC1 mouse model first described over 20 years ago. Phenotypic manifestations include macrosomia, macrocephaly, developmental delay, alopecia, spasticity, hypotonia, cutaneous vascular malformation, delayed visual maturation, and sensorineural hearing loss. We here describe for the first time a new pediatric disorder that is directly linked to a de novo pathogenic variant in the ODC1 gene. The ODC1 gene mutation (c.1342 A>T) was identified by whole-exome sequencing and confirmed by Sanger sequencing. Red blood cells obtained from our patient showed elevated ODC protein and polyamine levels compared to healthy controls. Our autosomal dominant patient who carries this gain-of-function ODC1 mutation may benefit from treatment with α-difluoromethylornithine, a well-tolerated, ...Continue Reading

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Citations

Nov 9, 2018·The Journal of Biological Chemistry·André S Bachmann, Dirk Geerts
Dec 21, 2018·American Journal of Medical Genetics. Part a·Carlos R Ferreira
May 30, 2019·American Journal of Medical Genetics. Part a·Maximilian Muenke
Sep 29, 2019·International Journal of Molecular Sciences·Kamyar ZahediManoocher Soleimani
Dec 14, 2018·Medical Sciences : Open Access Journal·Tracy Murray-StewartRobert A Casero
Mar 30, 2019·Frontiers in Nutrition·Bruno Ramos-MolinaRafael Peñafiel
Oct 16, 2020·Journal of Neuroinflammation·Kamyar ZahediManoocher Soleimani
Nov 20, 2020·Brain : a Journal of Neurology·Danique Beijer, Jonathan Baets
Apr 4, 2021·Genes·Jeremy W ProkopAndré S Bachmann
Jun 3, 2021·Medical Sciences : Open Access Journal·Shima Nakanishi, John L Cleveland
Jun 16, 2021·Cancer Chemotherapy and Pharmacology·Chad R SchultzAndré S Bachmann
Sep 4, 2021·American Journal of Medical Genetics. Part a·Elizabeth A VanSickleCaleb P Bupp
Oct 26, 2021·Journal of Medicinal Chemistry·Mukund P TantakOtto Phanstiel

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