Monogenic short stature

Gene: KHDC3L

Comment on mode of inheritance: MOI based on review from Professor Karen Temple (Clinical Genetics, University Hospital Southampton NHS Foundation Trust).

Created: 2 Feb 2021, 4:13 p.m. | Last Modified: 2 Feb 2021, 4:13 p.m.

Panel Version: 1.54

Red List (low evidence)

This is another maternal affect gene that predisposes to multi locus imprinting disturbance and can likely cause a phenoytpe in the Silver Russell spectrum. Findings of mutations in the mother would lead to methylation testing in the offspring/ proband/ products of cenception. Although there are not many examples of SRS being caused by this gene it is likely that it will be a cause given that it causes recurrent hydatidiform mole (which is a severe form of MLID testing)
Sources: Expert list

Created: 29 Jan 2021, 11:36 a.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
IUGR; Failure to thrive; hydatidiform mole; pregnancy loss

Publications

• Begemann, M., Rezwan, F. I., Beygo, J., Docherty, L. E., Kolarova, J., Schroeder, C., Karin Buiting, Kamal Chokkalingam, Franziska Degenhardt, Emma L Wakeling, Stephanie Kleinle, Daniela González Fassrainer, Barbara Oehl-Jaschkowitz, Claire L S Turner, Michal Patalan, Maria Gizewska, Gerhard Binder, Can Thi Bich Ngoc, Vu Chi Dung, Sarju G Mehta, Gareth Baynam, Julian P Hamilton-Shield, Sara Aljareh, Oluwakemi Lokulo-Sodipe, Rachel Horton, Reiner Siebert, Miriam Elbracht, I Karen Temple, Thomas Eggermann, Mackay, D. J. G.. Maternal variants in NLRP and other maternal-effect proteins are associated with multi-locus imprinting disturbance in offspring. Journal of Medical Genetics, 2018 55:497–504. PMID: 29574422 DOI: 10.1136/jmedgenet-2017-105190
• PMC6047157