Table 1
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Clinical and genetic data for Cases 1–7

Case 1Case 2Case 3Case 4Case 5Case 6Case 7
Main clinical featuresAtaxiaAtaxia, intellectual disabilityAtaxia, intellectual disabilityAtaxia, intellectual disabilityAtaxia, intellectual disabilityAtaxia, intellectual disability, febrile convulsions, low CoQ levels of unknown significanceAtaxia, intellectual disability
Family historyNoneNoneNoneNoneNoneNoneNone
GestationTerm42 weeksTermTerm39 weeks41 weeks40 weeks and 3 days
Birth weight (g)2860N/A2730N/A350032104082
DeliveryNVDNVDNVDInduction/EMCSNVDNVDNVD
Previous miscarriagesNone3None11 TOP (unknown foetal abnormality); 1 ectopicnone1
Paternal age at conception (years)40343336403433
Evidence of clinical regressionNoNoNoNoNoNoNo
Age at most recent review124105867
Intellectual disabilityMildModerateModerateModerateMild with expressive speech delay (EQ 68)Mild requiring special school (IQ 81)Moderate, requiring special school
Brain imagingNormalNormalNormalMild cerebellar hypoplasia/ ‘atrophy’NormalMild atrophy of cerebellar vermisCerebellar hypoplasia
Mutated geneKCNC3ITPR1ITPR1SPTBN2None foundNone foundRecessive mutations identified in putative novel gene
Nucleotide1283C>T1759A>G4459_4460delinsGA1438C>TNot applicableNot applicableUnder investigation
ProteinT428IN602DS1487DR480WNot applicableNot applicableUnder investigation

  • Nucleotide conservation

  • PhyloP (-14.1-6.4)

  • GERP_RS (-12.3-6.17)

  • 4.64

  • 3.04

  • 3.11

  • 4.98

  • 5.13/6.10

  • 5.71/5.71

  • 3.68

  • 3.55

  • Not applicable

  • Not applicable

  • Not applicable

  • Not applicable

  • Under investigation

  • Under investigation

  • Amino acid conservation

  • PolyPhen2 (0-1)

  • SIFT (1-0)

  • 0.982 (probably damaging)

  • 0 (Deleterious)

  • 0.958 (probably damaging)

  • 0 (Deleterious)

  • 0.905 (possibly damaging)

  • 0 (Deleterious)

  • 1.0 (Damaging)

  • 0 (Deleterious)

  • Not applicable

  • Not applicable

  • Not applicable

  • Not applicable

  • Under investigation

  • Under investigation

Presence in dbSNPNoYes – annotated as pathogenicNoYes – annotated as pathogenicNot applicableNot applicableUnder investigation
Number of cases in Exome Variant Server0000Not applicableNot applicableUnder investigation
Functional domainYes – ion selective poreYes – IRBIT binding domainYes – CA8 binding domainYes – Spectrin repeat 2Not applicableNot applicableUnder investigation
Case 1Case 2Case 3Case 4Case 5Case 6Case 7
Main clinical featuresAtaxiaAtaxia, intellectual disabilityAtaxia, intellectual disabilityAtaxia, intellectual disabilityAtaxia, intellectual disabilityAtaxia, intellectual disability, febrile convulsions, low CoQ levels of unknown significanceAtaxia, intellectual disability
Family historyNoneNoneNoneNoneNoneNoneNone
GestationTerm42 weeksTermTerm39 weeks41 weeks40 weeks and 3 days
Birth weight (g)2860N/A2730N/A350032104082
DeliveryNVDNVDNVDInduction/EMCSNVDNVDNVD
Previous miscarriagesNone3None11 TOP (unknown foetal abnormality); 1 ectopicnone1
Paternal age at conception (years)40343336403433
Evidence of clinical regressionNoNoNoNoNoNoNo
Age at most recent review124105867
Intellectual disabilityMildModerateModerateModerateMild with expressive speech delay (EQ 68)Mild requiring special school (IQ 81)Moderate, requiring special school
Brain imagingNormalNormalNormalMild cerebellar hypoplasia/ ‘atrophy’NormalMild atrophy of cerebellar vermisCerebellar hypoplasia
Mutated geneKCNC3ITPR1ITPR1SPTBN2None foundNone foundRecessive mutations identified in putative novel gene
Nucleotide1283C>T1759A>G4459_4460delinsGA1438C>TNot applicableNot applicableUnder investigation
ProteinT428IN602DS1487DR480WNot applicableNot applicableUnder investigation

  • Nucleotide conservation

  • PhyloP (-14.1-6.4)

  • GERP_RS (-12.3-6.17)

  • 4.64

  • 3.04

  • 3.11

  • 4.98

  • 5.13/6.10

  • 5.71/5.71

  • 3.68

  • 3.55

  • Not applicable

  • Not applicable

  • Not applicable

  • Not applicable

  • Under investigation

  • Under investigation

  • Amino acid conservation

  • PolyPhen2 (0-1)

  • SIFT (1-0)

  • 0.982 (probably damaging)

  • 0 (Deleterious)

  • 0.958 (probably damaging)

  • 0 (Deleterious)

  • 0.905 (possibly damaging)

  • 0 (Deleterious)

  • 1.0 (Damaging)

  • 0 (Deleterious)

  • Not applicable

  • Not applicable

  • Not applicable

  • Not applicable

  • Under investigation

  • Under investigation

Presence in dbSNPNoYes – annotated as pathogenicNoYes – annotated as pathogenicNot applicableNot applicableUnder investigation
Number of cases in Exome Variant Server0000Not applicableNot applicableUnder investigation
Functional domainYes – ion selective poreYes – IRBIT binding domainYes – CA8 binding domainYes – Spectrin repeat 2Not applicableNot applicableUnder investigation

CoQ = coenzyme Q10; EMCS = emergency Caesarian section; N/A = not available; NVD = normal vaginal delivery; TOP = termination of pregnancy.

Table 1
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Clinical and genetic data for Cases 1–7

Case 1Case 2Case 3Case 4Case 5Case 6Case 7
Main clinical featuresAtaxiaAtaxia, intellectual disabilityAtaxia, intellectual disabilityAtaxia, intellectual disabilityAtaxia, intellectual disabilityAtaxia, intellectual disability, febrile convulsions, low CoQ levels of unknown significanceAtaxia, intellectual disability
Family historyNoneNoneNoneNoneNoneNoneNone
GestationTerm42 weeksTermTerm39 weeks41 weeks40 weeks and 3 days
Birth weight (g)2860N/A2730N/A350032104082
DeliveryNVDNVDNVDInduction/EMCSNVDNVDNVD
Previous miscarriagesNone3None11 TOP (unknown foetal abnormality); 1 ectopicnone1
Paternal age at conception (years)40343336403433
Evidence of clinical regressionNoNoNoNoNoNoNo
Age at most recent review124105867
Intellectual disabilityMildModerateModerateModerateMild with expressive speech delay (EQ 68)Mild requiring special school (IQ 81)Moderate, requiring special school
Brain imagingNormalNormalNormalMild cerebellar hypoplasia/ ‘atrophy’NormalMild atrophy of cerebellar vermisCerebellar hypoplasia
Mutated geneKCNC3ITPR1ITPR1SPTBN2None foundNone foundRecessive mutations identified in putative novel gene
Nucleotide1283C>T1759A>G4459_4460delinsGA1438C>TNot applicableNot applicableUnder investigation
ProteinT428IN602DS1487DR480WNot applicableNot applicableUnder investigation

  • Nucleotide conservation

  • PhyloP (-14.1-6.4)

  • GERP_RS (-12.3-6.17)

  • 4.64

  • 3.04

  • 3.11

  • 4.98

  • 5.13/6.10

  • 5.71/5.71

  • 3.68

  • 3.55

  • Not applicable

  • Not applicable

  • Not applicable

  • Not applicable

  • Under investigation

  • Under investigation

  • Amino acid conservation

  • PolyPhen2 (0-1)

  • SIFT (1-0)

  • 0.982 (probably damaging)

  • 0 (Deleterious)

  • 0.958 (probably damaging)

  • 0 (Deleterious)

  • 0.905 (possibly damaging)

  • 0 (Deleterious)

  • 1.0 (Damaging)

  • 0 (Deleterious)

  • Not applicable

  • Not applicable

  • Not applicable

  • Not applicable

  • Under investigation

  • Under investigation

Presence in dbSNPNoYes – annotated as pathogenicNoYes – annotated as pathogenicNot applicableNot applicableUnder investigation
Number of cases in Exome Variant Server0000Not applicableNot applicableUnder investigation
Functional domainYes – ion selective poreYes – IRBIT binding domainYes – CA8 binding domainYes – Spectrin repeat 2Not applicableNot applicableUnder investigation
Case 1Case 2Case 3Case 4Case 5Case 6Case 7
Main clinical featuresAtaxiaAtaxia, intellectual disabilityAtaxia, intellectual disabilityAtaxia, intellectual disabilityAtaxia, intellectual disabilityAtaxia, intellectual disability, febrile convulsions, low CoQ levels of unknown significanceAtaxia, intellectual disability
Family historyNoneNoneNoneNoneNoneNoneNone
GestationTerm42 weeksTermTerm39 weeks41 weeks40 weeks and 3 days
Birth weight (g)2860N/A2730N/A350032104082
DeliveryNVDNVDNVDInduction/EMCSNVDNVDNVD
Previous miscarriagesNone3None11 TOP (unknown foetal abnormality); 1 ectopicnone1
Paternal age at conception (years)40343336403433
Evidence of clinical regressionNoNoNoNoNoNoNo
Age at most recent review124105867
Intellectual disabilityMildModerateModerateModerateMild with expressive speech delay (EQ 68)Mild requiring special school (IQ 81)Moderate, requiring special school
Brain imagingNormalNormalNormalMild cerebellar hypoplasia/ ‘atrophy’NormalMild atrophy of cerebellar vermisCerebellar hypoplasia
Mutated geneKCNC3ITPR1ITPR1SPTBN2None foundNone foundRecessive mutations identified in putative novel gene
Nucleotide1283C>T1759A>G4459_4460delinsGA1438C>TNot applicableNot applicableUnder investigation
ProteinT428IN602DS1487DR480WNot applicableNot applicableUnder investigation

  • Nucleotide conservation

  • PhyloP (-14.1-6.4)

  • GERP_RS (-12.3-6.17)

  • 4.64

  • 3.04

  • 3.11

  • 4.98

  • 5.13/6.10

  • 5.71/5.71

  • 3.68

  • 3.55

  • Not applicable

  • Not applicable

  • Not applicable

  • Not applicable

  • Under investigation

  • Under investigation

  • Amino acid conservation

  • PolyPhen2 (0-1)

  • SIFT (1-0)

  • 0.982 (probably damaging)

  • 0 (Deleterious)

  • 0.958 (probably damaging)

  • 0 (Deleterious)

  • 0.905 (possibly damaging)

  • 0 (Deleterious)

  • 1.0 (Damaging)

  • 0 (Deleterious)

  • Not applicable

  • Not applicable

  • Not applicable

  • Not applicable

  • Under investigation

  • Under investigation

Presence in dbSNPNoYes – annotated as pathogenicNoYes – annotated as pathogenicNot applicableNot applicableUnder investigation
Number of cases in Exome Variant Server0000Not applicableNot applicableUnder investigation
Functional domainYes – ion selective poreYes – IRBIT binding domainYes – CA8 binding domainYes – Spectrin repeat 2Not applicableNot applicableUnder investigation

CoQ = coenzyme Q10; EMCS = emergency Caesarian section; N/A = not available; NVD = normal vaginal delivery; TOP = termination of pregnancy.

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