FamilyKDC: Korea

FamilyPresentingHPOs: HP:0001251, HP:0002321, HP:0002018 (Ataxia, Vertigo, Nausea)

HPOsFreeText: N/A

FamilyNotHPOs: N/A

NotHPOsFreeText: N/A

FamilyGenotypingMethod: Genomic DNA was extracted fom patient blood samples. Whole exome sequencing was performed. Sequence variants in KCNA1, CACNA1A, CACNB4 and SLC1A3 were all searched with pathogenicity-based variant filtering. The found variant was further confirmed via PCR and Sanger sequencing.

FamilyPreviousTesting: Ataxic episodes usually provoked by stress; Responded to treatment with acetazolamide

FamilyAddInfo: N/A

Variant: NM_004172.5:c.1177G>A (p.Val393Ile)

CAID: CA3235626, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA3235626

gnomAD: 0.0002940, https://gnomad.broadinstitute.org/variant/5-36680579-G-A NOTE FREQUENCY VERY HIGH

Affected: 2

Segregations: 1

AddSegregationInfo: NOTE INCONSISTENT SEGREGATIONS, Not enough info to count, Pedigree in Figure 1A

FamilyDEVR: Europe

FamilyPresentingHPOs: HP:0002078, HP:0002066, HP:0002321, HP:0002017, HP:0000613, HP:0002183, HP:0000639 (Truncal ataxia, Gait ataxia, Vertigo, Nausea and vomiting, Photophobia, Phonophobia, Nystagmus)

HPOsFreeText: N/A

FamilyNotHPOs: HP:0002411 (Myokymia)

NotHPOsFreeText: N/A

FamilyGenotypingMethod: Genomic DNA was isolated from peripheral leukocytes. All exons and flanking introns of the SLC1A3 gene were amplified and sequenced. Restriction digest verified the results.

FamilyPreviousTesting: Attacks were generally triggered by emotional stress, with some triggered by fatigue; Acetazolamide significantly reduced the frequency of attacks in all 3 affected family members;

FamilyAddInfo: N/A

Variant: NM_004172.5(SLC1A3):c.556T>A (p.Cys186Ser)

ClinVar: 9442, https://www.ncbi.nlm.nih.gov/clinvar/variation/9442/

gnomAD: Not in gnomAD

Affected: 4

Segregations: 2

AddSegregationInfo: Not enough info

CasePAII-1: Female, 18 yrs onset

CasePresentingHPOs: HP:0000147, HP:0040292, HP:0002083, HP:0003401, HP:0001251, HP:0000640, HP:0006855, HP:0006744 (Polycystic ovary disease, Left hemiplegia, Migraine without aura, Paresthesia, Ataxia, Gaze-evoked nystagmus, Cerebellar vermis atrophy, Adrenocortical carcinoma)

HPOsFreeText: N/A

CaseNotHPOs: HP:0000505 (Visual impairments)

NotHPOsFreeText: N/A

CaseAddInfo: Parents are consanguineous, Mother has similar symptoms but declined to be clinically examined

CasePreviousTesting: Episodes triggered by menstruation but also by stress and preceded by a sensorimotor march; EEG and electroneurography were normal; Pathologic CAG expansions in CACNA1A and conventional mutations in CACNA1A, ATP1A2, and SCN1A were ruled out; Treatment with ACZ (250 mg twice daily) prevented hemiplegic spells and interictal GEN receded; MRS demonstrated low combined glutamate and glutamine peak that responded to ACZ treatment during an episode

CaseGenotypingMethod: Targeted genotyping analysis was performed.

Variant: NM_004172.5:c.379_383del (p.Tyr127Aspfs*60)

CAID: CA1139532263, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA1139532263

gnomAD: Not in gnomAD

CaseIW: Female, 10 yrs report,

CasePresentingHPOs: HP:0002078, HP:0000486, HP:0002080, HP:0001350 (Truncal ataxia, Strabismus, Intention tremor, Slurred speech)

HPOsFreeText: Hypoperfusion of cerebellum and brainstem at 8 yrs

CaseNotHPOs: HP:0001270 (Motor delay)

NotHPOsFreeText: N/A

CaseAddInfo: Parents are healthy and non-consanguineous and have no family history of neurological symptoms; Proband is confirmed de novo heterozygous via parental testing

CasePreviousTesting: Treatment with acetazolamide helped with symptoms

CaseGenotypingMethod: Genomic DNA was isolated from peripheral blood leukocytes and subject to whole exome sequencing. Variants were filtered according to likely pathogenicity and presence in previously reported causative genes associated with ataxia, cerebellar atrophy, and other neurodegenerative diseases.The SLC1A3 variant was confirmed via Sanger seuqencing in the proband and absent in her parents.

Variant: NM_004172.5:c.383T>G (p.Met128Arg)

CAID: CA359477326, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA359477326

gnomAD: Not in gnomAD