Rare anaemiaGene: NHLRC2
Comment on list classification: On recommendation of Genomics England clinical team, changing rating from red to amber with recommendation of review by the GMS with regards to phenotypic fit for this panel. Sufficient cases to make green if appropriate.
Created: 23 Dec 2020, 4:05 p.m. | Last Modified: 23 Dec 2020, 4:08 p.m.
Panel Version: 1.6
PMID: 29423877 Uusimaa et al 2018 - report 3 patients from 2 unrelated non-consanguineous Finnish families in which the children were born asymptomatic but by 2 months of age they had developed a progressive multi-organ disorder. The main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. All three patients were found using WES to be compound heterozygous for NM_198514:c.442G>T, p.Asp148Tyr and c.601_602delAG, p.Arg201GlyfsTer6. Segregation data for both families is provided. The family history of the two families, traced back 7–9 generations, showed that they did not have common ancestors. Both variants are rare in both Finnish (Sequencing Initiative Suomi - 0.003 and 0.0001 respectively) and non-Finnish populations (Exac). Patient fibroblasts expressed only mRNA with the c.442G>T missense variant, and at low levels. Development of Nhlrc2 null mice stalled before the morula stage. Morpholino knockdown of nhlrc2 in zebrafish embryos showed that nhlrc2 has a role in cellular integrity of the central nervous system during development.
PMID: 32435055 - Brodsky et al 2020 - report a 2 year old Ukranian patient with FINCA syndrome who was found by WES to have compound heterozygous variants in NHLRC2 (c.442T>G, p.D148Y and c.428C>A, p.H143P). The c.428C>A variant is not found in the gnomAD database. Each parent was a carrier for one of the variants.
Created: 23 Dec 2020, 4:03 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
FINCA syndrome OMIM:618278
Gene: nhlrc2 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: NHLRC2.
gene: NHLRC2 was added gene: NHLRC2 was added to Rare anaemia. Sources: Literature Mode of inheritance for gene: NHLRC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NHLRC2 were set to 29423877; 32435055 Phenotypes for gene: NHLRC2 were set to FINCA syndrome OMIM:618278 Review for gene: NHLRC2 was set to GREEN