Monogenic short stature

Gene: NLRP7

Submitted on behalf of NHS GMS "This gene does not go on the panel as linked to MLID and suggest separate panel for this. Genes NLRP5, NLRP7, PAD16, NLRP2 & KHDC3L"

Created: 3 Mar 2022, 1:49 p.m. | Last Modified: 3 Mar 2022, 1:49 p.m.

Panel Version: 1.100

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.

Created: 3 Mar 2022, 1:49 p.m. | Last Modified: 3 Mar 2022, 1:49 p.m.

Panel Version: 1.100

Green List (high evidence)

Comment on mode of inheritance: Review from Eamonn Maher: I think it would be better that these are maternal effect genes for which biallelic variants in a healthy women cause a reproductive phenotype that may include miscarriage, hydatidiform mole or children with a congenital imprinting disorder

Created: 21 Apr 2021, 2:43 p.m. | Last Modified: 21 Apr 2021, 2:43 p.m.

Panel Version: 1.61

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, 2:36 p.m. | Last Modified: 2 Feb 2021, 2:36 p.m.

Panel Version: 1.50

Comment on list classification: Based on review from Professor Karen Temple (Clinical Genetics, University Hospital Southampton NHS Foundation Trust) for the involvement of NLRP7 variants in Multi Locus Imprinting Disturbance

Created: 1 Feb 2021, 8:53 a.m. | Last Modified: 2 Feb 2021, 2:47 p.m.

Panel Version: 1.52

Green List (high evidence)

NOte that this gene is tested for in recurrent hydatidiform mole. But some pregnancies progress with growth disorders due to multilocus imprinting disturbance. This can missed on genome testing and so patients require methylation testing at imprinted loci to confirm The mutation in NLRP7 is in the mother of the proband.
Sources: Expert list

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

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
IUGR; Short stature; fetal wastage

Publications

• Eur J Hum Genet. 2017 Aug
• 25(8):924-929. PMID: 28561018 doi: 10.1038/ejhg.2017.94. Epub 2017 May 31. Maternal heterozygous NLRP7 variant results in recurrent reproductive failure and imprinting disturbances in the offspring. Soellner L(1), Begemann M(1), Degenhardt F(2), Geipel A(3), Eggermann T(1), Mangold E(2).