family C, the two affected individuals were compound heterozygous for the frameshift c.406delC (p.Pro136Argfs∗40) mutation and the splicing c.1605+5G>A mutation.
Variant NM_005186.3(CAPN1):c.407delC (p.Pro136Argfs), NM_001198868.1(CAPN1):c.1605+5G>A
ClinVar 225767, 225768
gnomAD none, 0.0003171
family C, the two affected individuals
Case# FamilyC:IV-13, 33 AoO, Female, USA
CasePresentingHPOs HP:0002064, HP:0001258, HP:0002355
CaseMethod1 WES
CaseMethod2 Sanger
Variant NM_005186.3(CAPN1):c.407delC (p.Pro136Argfs), NM_001198868.1(CAPN1):c.1605+5G>A
ClinVar 225767, 225768
gnomAD none, 0.0003171
CaseAddInfo nonconsanguineous family
family B
Family#PresentingHPOs HP:0001258, HP:0002460, HP:0007067, HP:0002395
CountryOrigin Morocco
Race White
Family#Method1 WES
Family#Method2 Sanger
Affected 4
Unaffected 3
Segregations 4
eLOD 1.93
AddSegregationInfo consanguineous
ProbandLabel FamilyB:IV-1 age of onset 35, Male
Variant NM_001198868.1(CAPN1):c.1579C>T (p.Gln527Ter)
ClinVar 225766
FamilyAddInfo Fig 1
family C, the two affected individuals were compound heterozygous for the frameshift c.406delC (p.Pro136Argfs∗40) mutation and the splicing c.1605+5G>A mutation.
Variant NM_005186.3(CAPN1):c.407delC (p.Pro136Argfs), NM_001198868.1(CAPN1):c.1605+5G>A
ClinVar 225767, 225768
gnomAD none, 0.0003171
family C, the two affected individuals
Case# FamilyC:IV-13, 33 AoO, Female, USA
CasePresentingHPOs HP:0002064, HP:0001258, HP:0002355
CaseMethod1 WES
CaseMethod2 Sanger
Variant NM_005186.3(CAPN1):c.407delC (p.Pro136Argfs), NM_001198868.1(CAPN1):c.1605+5G>A
ClinVar 225767, 225768
gnomAD none, 0.0003171
CaseAddInfo nonconsanguineous family
family B
Family#PresentingHPOs HP:0001258, HP:0002460, HP:0007067, HP:0002395
CountryOrigin Morocco
Race White
Family#Method1 WES
Family#Method2 Sanger
Affected 4
Unaffected 3
Segregations 4
eLOD 1.93
AddSegregationInfo consanguineous
ProbandLabel FamilyB:IV-1 age of onset 35, Male
Variant NM_001198868.1(CAPN1):c.1579C>T (p.Gln527Ter)
ClinVar 225766
FamilyAddInfo Fig 1
A 54-year-old female proband
Case# Fam2Pat1, F, Turkish, 15yo onset
CasePresentingHPOs HP:0002061, HP:0002066, HP:0002070, HP:0001260, HP:0001310, HP:0000563, HP:0006986
CasePreviousTesting Neurologic examination revealed severe spasticity in the lower and mild spasticity in the upper extremities, hyperactive deep tendon reflexes, bilateral extensor plantar responses, and patellar clonus. The Hoffmann sign was positive. She had bilateral mild dysmetria and dysdiadochokinesia. Nerve conduction studies, EMG, sensory evoked potential tests, and MRI did not reveal any pathology
CaseMethod1 Whole Exome
Variant NM_001198869.1:c.1176G>A
CAID CA6093326
VariantEvidence premature stop codon
gnomAD 1.554e-05(European (Non-Finnish)), 8.513e-06(Overall)-Exac
A 54-year-old female proband
Case# Fam2Pat1, F, Turkish, 15yo onset
CasePresentingHPOs HP:0002061, HP:0002066, HP:0002070, HP:0001260, HP:0001310, HP:0000563, HP:0006986
CasePreviousTesting Neurologic examination revealed severe spasticity in the lower and mild spasticity in the upper extremities, hyperactive deep tendon reflexes, bilateral extensor plantar responses, and patellar clonus. The Hoffmann sign was positive. She had bilateral mild dysmetria and dysdiadochokinesia. Nerve conduction studies, EMG, sensory evoked potential tests, and MRI did not reveal any pathology
CaseMethod1 Whole Exome
Variant NM_001198869.1:c.1176G>A
CAID CA6093326
VariantEvidence premature stop codon
gnomAD 1.554e-05(European (Non-Finnish)), 8.513e-06(Overall)-Exac
SAL-584-005
Case# SAL-584-005, Female, 67yo, Italian
CasePresentingHPOs HP:0001258, HP:0002070, HP:0001260, HP:0002066
CaseMethod1 Exome
CaseMethod2 Sanger
Variant NM_005186.3:c.188dup
CAID CA6092966
gnomAD 0.000009815
VariantEvidence null
CaseAddInfo in supplement, possibly consanguineous family
index patient in family R
Case# Family R III:1, Female, 43yo, Bangladesh
CasePresentingHPOs HP:0002066, HP:0001257, HP:0002015, HP:0001260, HP:0001272
CaseMethod1 DNA SNP array
CaseMethod2 Exome sequencing
Variant NM_005186.3:c.337+1G>A
CAID CA381241741
VariantEvidence predicted null
SAL-584-005
Case# SAL-584-005, Female, 67yo, Italian
CasePresentingHPOs HP:0001258, HP:0002070, HP:0001260, HP:0002066
CaseMethod1 Exome
CaseMethod2 Sanger
Variant NM_005186.3:c.188dup
CAID CA6092966
gnomAD 0.000009815
VariantEvidence null
CaseAddInfo in supplement, possibly consanguineous family
index patient in family R
Case# Family R III:1, Female, 43yo, Bangladesh
CasePresentingHPOs HP:0002066, HP:0001257, HP:0002015, HP:0001260, HP:0001272
CaseMethod1 DNA SNP array
CaseMethod2 Exome sequencing
Variant NM_005186.3:c.337+1G>A
CAID CA381241741
VariantEvidence predicted null