This report describes a Drosophila model of IMAGe syndrome. The gene implicated in this disease is CDKN1C (cyclin-dependent kinase inhibitor 1C), an inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. IMAGe syndrome is inherited in an autosomal dominant manner, but because the gene is subject to genomic imprinting only maternal transmission of a pathogenic variant results in IMAGe syndrome. There are multiple similar cyclin-dependent kinase inhibitors in both species, but none of the fly genes is closely related to CDKN1C.
CDKN1C is also implicated in a second disease (Beckwith-Wiedemann Syndrome, MIM:130650); this Drosophila model makes use of two variants specifically associated with IMAGe syndrome.
Multiple UAS constructs of the human Hsap\CDKN1C gene have been introduced into flies, including wild-type and variants associated with IMAGe syndrome. This work in flies supported identification of CDKN1C variants as causative in development of IMAGe syndrome. Variant(s) implicated in human disease tested (as transgenic human gene, CDKN1C): the F276V and K278E variant forms have been introduced into flies; both of these variants are implicated in IMAGe syndrome. Other CDKN1C variants tested: L42P, c.826delT.
[updated Sep. 2017 by FlyBase; FBrf0222196]
[INTRAUTERINE GROWTH RETARDATION, METAPHYSEAL DYSPLASIA, ADRENAL HYPOPLASIA CONGENITA, AND GENITAL ANOMALIES; IMAGE](https://omim.org/entry/614732)
[CYCLIN-DEPENDENT KINASE INHIBITOR 1C; CDKN1C](https://omim.org/entry/600856)
IMAGE syndrome is characterized by intrauterine growth retardation, severe adrenal insufficiency, skeletal abnormalities, genital abnormalities in males, and mild dysmorphic features. [from MIM:137215; 2017.09.11]
CDKN1C is located within an imprinted cluster of genes on chromosome 11 that regulate prenatal and postnatal growth and development. [Genetics Home Reference, CDKN1C; 2017.09.11]
A CDKN1C pathogenic variant causing IMAGe syndrome is inherited in an autosomal dominant manner, however, only maternal transmission of the pathogenic variant results in IMAGe syndrome. [Gene Reviews, IMAGe Syndrome; 2017.09.11]
CDKN1C is subject to genomic imprinting, with preferential expression of the maternal allele. [Gene Cards, CDKN1C; 2017.09.11]
IMAGE syndrome can be caused by heterozygous mutation in the CDKN1C gene [from MIM:614732; 2017.09.11]
The CDKN1C gene encodes Cyclin Dependent Kinase Inhibitor 1C, a tight-binding, strong inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. It may play a role in maintenance of the non-proliferative state throughout life (may act as a tumor suppressor gene). [Gene Cards, CDKN1C; 2017.09.11]
There are multiple similar genes in both species, but none of the fly genes is closely related to CDKN1C.
