Severe microcephaly
Gene: TP53RKThe 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
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
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 ReviewCreated: 4 Sep 2020, 2:16 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Galloway-Mowat syndrome 4, MIM# 617730
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q2_21_rating was removed from gene: TP53RK.
Source Expert Review Green was added to TP53RK. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: tp53rk has been classified as Amber List (Moderate Evidence).
Tag Q2_21_rating tag was added to gene: TP53RK.
Phenotypes for gene: TP53RK were changed from Galloway-Mowat syndrome 4, MIM# 617730 to Galloway-Mowat syndrome 4, OMIM:617730
gene: TP53RK was added gene: TP53RK was added to Severe microcephaly. Sources: Expert Review Mode of inheritance for gene: TP53RK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TP53RK were set to 28805828; 30053862 Phenotypes for gene: TP53RK were set to Galloway-Mowat syndrome 4, MIM# 617730 Review for gene: TP53RK was set to GREEN gene: TP53RK was marked as current diagnostic