Mackenzie's Mission_Reproductive Carrier Screening

Gene: ADPRHL2

I agree this is a straightforward GREEN for Mackenzie's Mission. Clearly severe enough phenotype and meets evidence criteria. Only two publications (three if you count PMC5589982) but both with multiple families, consistent phenotype. Change of gene symbol important to note from pipeline point of view.

Note - I don't think I selected a rating when I entered the above, not certain if this matters.

Created: 6 Dec 2020, 5:27 a.m. | Last Modified: 6 Dec 2020, 5:31 a.m.

Panel Version: 0.49

Green List (high evidence)

Fourteen unrelated families reported with stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS), an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. The disorder is characterised by cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some individuals develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy.

New HGNC approved name is ADPRS.
Sources: Expert Review

Created: 12 Sep 2020, 1:45 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MIM#618170

Publications

• 30100084
• 30401461