Likely inborn error of metabolism

Gene: KIAA0391

Green List (high evidence)

Comment on list classification: KIAA0391 (PRORP) has already been promoted to green rating on Mitochondrial disorders panel (https://panelapp.genomicsengland.co.uk/panels/112/gene/KIAA0391/) as detailed in the below reviews copied from that panel.

As there is sufficient evidence available for the gene-disease association, this gene can be promoted to green rating on this panel in the next GMS update.

Created: 7 Jun 2025, 9:38 p.m. | Last Modified: 7 Jun 2025, 9:38 p.m.

Panel Version: 8.27

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency 54, OMIM:619737

Green List (high evidence)

PRORP is the HGNC approved gene name for KIAA0391 https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:19958

Created: 9 Dec 2021, 5:26 p.m. | Last Modified: 9 Dec 2021, 5:26 p.m.

Panel Version: 2.64

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 9 Dec 2021, 5:24 p.m. | Last Modified: 9 Dec 2021, 5:24 p.m.

Panel Version: 2.64

Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID 34715011 reports six variants in four unrelated families with pleiotropic multisystem presentations. The authors of this report that the PRORP should be
considered another as another gene be associated with the Perrault syndrome clinical spectrum.

Created: 9 Dec 2021, 5:23 p.m. | Last Modified: 9 Dec 2021, 5:23 p.m.

Panel Version: 2.63

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Perrault syndrome clinical spectrum

Green List (high evidence)

Four unrelated families with multisystem disease associated with bi-allelic variants in PRORP, HGNC approved name is KIAA0391. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes.

-1 consanguineous family with homozygous missense in 3 affected sisters, het parents unaffected. Siblings had profound bilateral SNHL in infancy. In teens developed primary amenorrhea/Perrault syndrome, and hypergonadotropic hypogonadism.
-1 unrelated male with compound het missense, each inherited from an unaffected parent. Hearing loss noted at 3, diagnosed at 5.
-1 unrelated male compound het for a missense and a frameshift. appendicular hypertonia in infancy, mild dysmorphism. Severe global dev delay at 20 months. Normal hearing at 18 months, but at 3 years had bilateral SNHL.
-an affected mother and her 2 affected children (son and daughter), homozygous for a missense. Father is heterozygous and unaffected. Son has psychotic disorder, autistic traits. Sister had intrauterine growth retardation, global developmental delay, and seizures in the first years of life. Mother presented with retrobulbar optic neuritis and tonic pupil at 39 years of age, then with asthenia, myalgias, memory loss, and frequent headaches.
Sources: Literature

Created: 4 Dec 2021, 7:59 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hearing loss, intellectual disability

Publications

• 34715011

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