White matter disorders and cerebral calcification - narrow panel

Gene: KIAA1161

Green List (high evidence)

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

Created: 30 Jan 2023, 4:26 p.m. | Last Modified: 30 Jan 2023, 4:26 p.m.

Panel Version: 2.9

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.

Created: 28 Jun 2021, 12:53 p.m. | Last Modified: 28 Jun 2021, 12:53 p.m.

Panel Version: 1.186

Comment on mode of inheritance: MOI has been changed from "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" to "Biallelic, autosomal or pseudoautosomal" after consulting the Genomics England Clinical Team. As not all carriers exhibit the phenotype and the age of for the carriers that do exhibit the phenotype is not appropriate for this panel. Therefore the Biallelic MOI was assigned.

Created: 28 Jun 2021, 12:41 p.m. | Last Modified: 28 Jun 2021, 12:41 p.m.

Panel Version: 1.185

Comment on publications: PMID: 31951047 - "89.5% (34 of 38) of individuals with heterozygous mutations remained asymptomatic at the time of examination and 4 of them exhibited symptoms with uncertain clinical significance (nonspecific depression, epilepsy, and late‐onset parkinsonism)". Age at CT scans range from 28-84. "brain calcifications of varying severity, from mild calcifications limited to the basal ganglia that were hard to differentiate from physiological calcifications to diffuse and moderate calcium deposits".

PMID: 30656188 - 2 families, carriers were all asymptomatic. Family 1 had no calcifications/no information. Family 2, 3/4 carriers had symmetrical punctuate calcification limited to the globus pallidus. The carriers were scanned <40yo.

PMID: 30895394 - proband's father (carrier) had diffuse bilateral cerebral calcifications with no symptoms other than very mild postural tremor. Scan age 68.

PMID: 31009047 - 3 families. Fathers of all probands were carriers. 2 had lenticulo-cerebellar calcifications - one of these 2 carriers had depression and cognitive impairment (age unknown), the other carrier was asymptomatic and was 65 yo when scan was done. 3rd father had calcifications restricted to the lenticular nuclei and was asymptomatic (age unknown).

Created: 28 Jun 2021, 12:32 p.m. | Last Modified: 28 Jun 2021, 12:32 p.m.

Panel Version: 1.184

added new-gene-name tag, new approved HGNC gene symbol for KIAA1161 is MYORG

Created: 12 May 2021, 2:11 p.m. | Last Modified: 12 May 2021, 2:11 p.m.

Panel Version: 1.88

Green List (high evidence)

PMID 31951047: In a cohort study comprising 435 individuals with primary brain calcification, 38 individuals identified with mono-allelic variants in this gene, in addition to 14 with bi-allelic variants. Clinical and imaging penetrance of individuals with bi-allelic variants were 100%, whereas among individuals with heterozygous variants, penetrance of imaging phenotype was reduced to 73.7% (28 of 38) and clinical penetrance was much lower. Most (34 of 38) remained asymptomatic whereas 4 had symptoms of uncertain clinical significance (nonspecific depression, epilepsy and late-onset parkinsonism). Compared with individuals with biallelic MYORG variants, individuals with heterozygous variants had brain calcifications with much lower calcification scores (P < 2e-16). HGNC approved name is MYORG.

Note additional publications supporting association with bi-allelic variants.
Sources: Literature

Created: 5 Oct 2020, 9:01 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

• 30656188
• 30649222
• 30460687
• 29910000
• 31951047