Gain ‐of‐function variants in the ODC1 gene cause a syndromic neurodevelopmental disorder associated with macrocephaly, alopecia, dysmorphic features, and neuroimaging abnormalities

In this report, we present four patients with a distinct neurometabolic disorder associated with de novo heterozygous, gain‐of‐function variants in theODC1 gene. This disorder presents with global developmental delay, ectodermal abnormalities including alopecia, absolute or relative macrocephaly, and characteristic facial dysmorphisms. Neuroimaging variably demonstrates white matter abnormalities, prominent Virchow –Robin spaces, periventricular cysts, and abnormalities of the corpus callosum. Plasma clinical metabolomics analysis demonstrates elevation ofN‐acetylputrescine, the acetylated form of putrescine, with otherwise normal polyamine levels. Therapies aimed at reducing putrescine levels, including ODC1 inhibitors, dietary interventions, and antibiotics to reduce polyamine production by gastrointestinal flora could be considered as disease‐m odifying therapies. As theODC1 gene has been implicated in neoplasia, cancer surveillance may be important in this disorder.

Source: American Journal of Medical Genetics Part A - November 26, 2018 Category: Genetics & Stem Cells Authors: Lance H. Rodan, Kwame Anyane ‐Yeboa, Karen Chong, Jolien S. Klein Wassink‐Ruiter, Ashley Wilson, Lacey Smith, Sanjeev V. Kothare, Farrah Rajabi, Susan Blaser, Min Ni, Ralph J. DeBerardinis, Annapurna Poduri, Gerard T. Berry Tags: RESEARCH ARTICLE Source Type: research