Possible mitochondrial disorder - nuclear genes

Gene: HSPA9

Green List (high evidence)

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

Created: 4 Dec 2024, 11:42 a.m. | Last Modified: 4 Dec 2024, 11:42 a.m.

Panel Version: 3.113

Comment on list classification: There is sufficient evidence available for the association of biallelic variants in HSPA9 gene to Even-plus syndrome. Hence, this gene should be promoted to green rating in the next GMS review.

Created: 16 Nov 2023, 1:20 p.m. | Last Modified: 16 Nov 2023, 1:20 p.m.

Panel Version: 3.68

As reviewed by Hannah Knight, there are more than three unrelated cases identified with biallelic HSPA9 variants and reported with Even-plus syndrome (MIM #616854).

However, there are only two unrelated families identified with monoallelic HSPA9 variants and reported with sideroblastic anemia-4 (MIM #182170) (PMID:26491070).

Created: 16 Nov 2023, 1:15 p.m. | Last Modified: 16 Nov 2023, 1:16 p.m.

Panel Version: 3.65

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Even-plus syndrome, OMIM:616854; Anemia, sideroblastic, 4, OMIM:182170

Publications

• 26491070
• 26598328
• 32869452
• 35779070
• 36052765

Green List (high evidence)

>3 independent cases now reported
PMID: 26598328 describes the identification of biallelic variants in HSPA9 in three patients (two of which are siblings), with EVEN-PLUS syndrome
PMID: 32869452 reported another patient
PMID: 35779070 reported two siblings
PMID: 36052765 reported first Chinese patient

Created: 2 Nov 2023, 9:09 a.m. | Last Modified: 2 Nov 2023, 9:09 a.m.

Panel Version: 3.51

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Even-plus syndrome 616854

Publications

• 26598328
• 32869452
• 35779070
• 36052765

Red List (low evidence)

Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group.

Created: 4 Feb 2019, 1:36 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Anemia, sideroblastic, 4, 182170; Even-plus syndrome, 616854; Also Parkinson disease association?

Comment on list classification: Discussed in the Analysis & Interpretation meeting and decided to make this red for now.

Created: 25 Apr 2016, 12:18 p.m.

Comment on list classification: PMID: 26598328 describes the identification of biallelic variants in HSPA9 in three patients (two of which are siblings), with EVEN-PLUS syndrome (a proposed syndrome name), and discussed the evidence for likely effect on HSPA9 function due to its role as a mitochondrial chaperone.

Created: 15 Feb 2016, 11:46 a.m.

Comment on mode of inheritance: One patient was compound heterozygous, the two siblings were homozygous for a seperate mutation. Unaffected parents were heterozygous.

Created: 15 Feb 2016, 11:44 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal