Intracerebral calcification disorders

Gene: FARSB

Green List (high evidence)

Comment on list classification: Following consultation with Helen Brittain (Genomics England Clinical Team), it was agreed that there is sufficient evidence/number of cases with the relevant phenotype to rate this gene Green.

Created: 12 Oct 2020, 1:08 p.m. | Last Modified: 12 Oct 2020, 1:32 p.m.

Panel Version: 1.24

Associated with Rajab interstitial lung disease with brain calcifications in OMIM, but not in G2P.

Biallelic variants are associated with a multisystem disorder characterised by interstitial lung disease, cerebral aneurysms and brain calcifications, cirrhosis, and failure to thrive.

Antonellis et al. (2018) (PMID: 29573043) - Compound heterozygous variants (c.767C>T, p.Thr256Met; c.1486delCinsAA, p.His496Lysfs*14) identified in a male. No report of brain calcification, however the patient died at 32 months. Expression studies using patient fibroblasts showed severe depletion in protein levels, with indication of a loss-off-function effect.

Xu et al. 2018 (PMID: 29979980) - five affected individuals from four families with biallelic FARSB variants. Brain calcifications were detected in three patients (from two families). The remaining two patients, brain MRI was not assessed in one, and showed no significant abnormality at 4 months in the other.

Zadjali et al. (2018) (PMID: 30014610) - eight affected individuals from a large consanguineous Omani family revealed homozygosity for a missense variant (c.853G>A, p.Glu285Lys). Widespread brain calcifications were evident among all affected individuals.

Created: 3 Aug 2020, 2:52 p.m. | Last Modified: 3 Aug 2020, 2:52 p.m.

Panel Version: 1.18

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 29573043
• 29979980
• 30014610

Green List (high evidence)

7 unrelated families reported.
Sources: Expert list

Created: 24 Jul 2020, 8:39 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Rajab syndrome, MIM#613658; interstitial lung disease; brain calcifications; microcephaly; intellectual disability

Publications

• 29573043
• 19161147
• 29979980
• 30014610

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