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Leukodystrophy v0.338 Bryony Thompson Copied gene APP from panel Leukodystrophy - adult onset
Leukodystrophy v0.338 APP Bryony Thompson gene: APP was added
gene: APP was added to Leukodystrophy - paediatric. Sources: Expert Review Green,Other
Mode of inheritance for gene: APP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: APP were set to 36845656
Phenotypes for gene: APP were set to early-onset autosomal dominant Alzheimer disease MONDO:0015140
Leukodystrophy v0.219 POLR3K Zornitza Stark gene: POLR3K was added
gene: POLR3K was added to Leukodystrophy - paediatric. Sources: Expert Review
Mode of inheritance for gene: POLR3K was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3K were set to 30584594; 33659930
Phenotypes for gene: POLR3K were set to Hypomyelinating leukodystrophy-21, MIM#619310
Review for gene: POLR3K was set to AMBER
Added comment: Two individuals from same ethnic background reported with a common homozygous missense variant in this gene, suggestive of founder effect. Some functional evidence, and note other gene family members are linked to similar phenotypes.

Neurodegenerative phenotype: global developmental delay apparent from infancy with loss of motor, speech, and cognitive milestones in the first decades of life.
Sources: Expert Review
Leukodystrophy v0.139 POLR3B Zornitza Stark gene: POLR3B was added
gene: POLR3B was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: POLR3B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLR3B were set to 27512013; 22036171; 22036172
Phenotypes for gene: POLR3B were set to Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism, MIM# 614381
Review for gene: POLR3B was set to GREEN
Added comment: More than 10 families reported. Early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism.
Sources: Expert list
Leukodystrophy v0.132 FDX2 Bryony Thompson gene: FDX2 was added
gene: FDX2 was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: FDX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDX2 were set to 30010796
Phenotypes for gene: FDX2 were set to Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy MIM#251900
Review for gene: FDX2 was set to AMBER
Added comment: Two apparently unrelated consanguineous Brazilian families reported with reversible leukoencephalopathy with a paediatric onset as a feature of the condition.
Sources: Expert list
Leukodystrophy v0.85 DARS Zornitza Stark gene: DARS was added
gene: DARS was added to Leukodystrophy - paediatric. Sources: Expert list
Mode of inheritance for gene: DARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DARS were set to 23643384
Phenotypes for gene: DARS were set to Hypomyelination with brainstem and spinal cord involvement and leg spasticity, MIM# 615281
Review for gene: DARS was set to GREEN
Added comment: Onset typically in infancy with lower limb spasticity. Brain MRI shows extensive white matter abnormalities involving the supratentorial white matter, brainstem, cerebellar peduncles, and dorsal columns and lateral corticospinal tracts of the spinal cord. HGNC approved name DARS1.
Sources: Expert list
Leukodystrophy v0.36 PRF1 Bryony Thompson gene: PRF1 was added
gene: PRF1 was added to Leukodystrophy - paediatric_RMH. Sources: Expert list
Mode of inheritance for gene: PRF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRF1 were set to 23443029; 21959744
Phenotypes for gene: PRF1 were set to Hemophagocytic lymphohistiocytosis, familial, 2 603553
Review for gene: PRF1 was set to RED
Added comment: Leukodystrophy does not appear to be a prominent feature of the condition
Sources: Expert list
Leukodystrophy v0.9 COQ8A Bryony Thompson gene: COQ8A was added
gene: COQ8A was added to Leukodystrophy - paediatric_RMH. Sources: Expert list
Mode of inheritance for gene: COQ8A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COQ8A were set to Coenzyme Q10 deficiency, primary, 4 612016
Review for gene: COQ8A was set to RED
Added comment: White matter changes don't appear to be a prominent feature of the condition.
Sources: Expert list
Leukodystrophy v0.3 AIMP2 Bryony Thompson gene: AIMP2 was added
gene: AIMP2 was added to Leukodystrophy - paediatric_RMH. Sources: Literature
Mode of inheritance for gene: AIMP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AIMP2 were set to 29215095
Phenotypes for gene: AIMP2 were set to Leukodystrophy, hypomyelinating, 17 618006
Review for gene: AIMP2 was set to RED
Added comment: Two apparently unrelated consanguineous families with the same truncating variant. The variant lies in a common homozygous region of 940 kb on chromosome 7 and is likely to have been inherited from a common ancestor. No functional analyses conducted.
Sources: Literature