Severe microcephaly

Gene: TP53RK

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 10 Mar 2022, 1:37 p.m. | Last Modified: 10 Mar 2022, 1:37 p.m.

Panel Version: 2.292

Green List (high evidence)

Comment on list classification: Promoting from grey to amber, but with a recommendation for green rating following GMS review. Following consultation with the Genomics England clinical team it was decided that a green recommendation would be appropriate as primary microcephaly might be the presenting feature before renal issues appear.

Created: 30 Jun 2021, 12:05 p.m. | Last Modified: 30 Jun 2021, 12:05 p.m.

Panel Version: 2.211

Associated with Galloway-Mowat syndrome 4 #617730 (AR) in OMIM with microcephaly as a clinical feature.

PMID:28805828 - Braun et al 2017 - using WES and high-throughput exon sequencing they screened the coding regions of OSGEP, TP53RK, TPRKB and LAGE3 in 907 individuals with Nephrotic syndrome including 91 individuals with Galloway-Mowat syndrome and found TP53RK mutations in 4 individuals from 3 families (2 siblings were compound het, 2 others were homozygous). Parents were heterozygous. All had primary microcephaly but the severity is not stated.

PMID:30053862 - Sun Hyan et al 2018 - report a family with 3 siblings with GAMOS in which a TP53RK mutation (NM_033550, c.194A > T, p.Lys65Met) was identified using WES. The 3 patients had similar phenotypes with very early-onset nephrotic syndrome (8 days, 1 day, and 1 day after birth, respectively), microcephaly, dysmorphic faces, and early fatality. Head circumference of all at birth was <3rd percentile.

Created: 26 May 2021, 9:58 p.m. | Last Modified: 26 May 2021, 9:58 p.m.

Panel Version: 2.187

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Galloway-Mowat syndrome 4, OMIM:17730

Publications

• 28805828
• 30053862

Green List (high evidence)

At least 4 unrelated families reported with renal-neurologic disease characterised by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities, and delayed psychomotor development. Most individuals have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable.
Sources: Expert Review

Created: 4 Sep 2020, 2:16 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Galloway-Mowat syndrome 4, MIM# 617730

Publications

• 28805828
• 30053862

Variants in this GENE are reported as part of current diagnostic practice