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Table 1 Genotype—phenotype correlations

From: Clinical profile of patients with ATP1A3 mutations in Alternating Hemiplegia of Childhood—a study of 155 patients

Genotype Phenotype of patients encountered in this study
Number of patients Age at onset: first event/first hemiplegic attack Age at last observation/Gender Intellectual disability Walking problems Ataxia Dystonia Hemiplegia/Double hemiplegia attacks Tonic attacks Epilepsy Other patients’ references
Cluster 1
 p.Ser137Phe 1 Unknown 20y / F ++ Unknown + + ++++ ++++ ++ [21, 31]
 p.Ser137Tyr 2 4 m / 4 m 9y / F ++ - + + ++++ Unknown Remission [21, 34, 35]
  2y / M + +   - ++++ - -
Cluster 2
p.Ala264_Ala289delinsValLeuGly 1 2 m / 2 m 34y / M - ++ (Regression- lost walking) - +++ + + -  
 p.Ile274Asn 1 Neonatal / 33 m 10y / M + - - + +++++ + - [21, 22, 31]
 p.Glu324Gln 1 1 m / 5 m 16y / M +++ ++ (Regression) - +++ ++++ ++++ - [31]
 p.Leu326Arg 1 8 m / 15 m 4y / F + - - - Remission Remission - [31]
c.993 + 1_993 + 2del $ 1 12 m / 12 m 6y / M - - - + +++ + Remission  
 p.Cys333Phe 1 1 m / 15 m 4y / M + + (Regression) - + ++++ +++ Remission [21, 31]
p.Gly358Ser 1 Neonatal / 6 years 11y / M +++ + +   +++++ ++++ ++++  
Cytoplasmic domain between Cluster 2 and 3
 p.Cys596Arg 1 1 m / 24 m 21y / M +++ - + + +++ +++ + [31]
p.Leu715Pro $ 1 Neonatal / 3 m 2y / M ++ ++ + + +++++ + +++++  
Cluster 3
 p.Gly755Ser 3 4 m / 5 m 24y / M - - Unknown ++ +++++ +++++ Remission [21, 31, 3335]
6 m / 8 m 8y / M + - ++ Unknown ++++ ++++ ++
6 m / 6 m 8y / M Unknown - + - ++++ - -
 p.Ser772Arg 2 9 m / 9 m 20y / M ++ + + ++ + + + [22, 31, 35]
5 m / 10 m 7y / M ++ - - ++ ++++ ++++ -
 p.Asn773Ser 2 mono-zygotic twins Neonatal / 22 m 10y / F + - - - ++ + Remission [21]
Neonatal / 22 m 10y / F + - - - +++ ++++ Remission
 p.Asp801Asn 57 2 m / 7 m (medians) Median 15.7y ++ - +++ ++ ++++ ++++ + [8, 2123, 31, 3335]
p.Asp801Val $ 1 21 m / 21 m 23y / M - - ++ + Remission ++++ -  
 p.Thr804Ile 2 2 m / 9 m 13y / F + - - + ++ ++ - [31, 33]
5 m / 5 m 10y / F ++ - + - ++ ++ -
 p.Met806Arg 1 13 m / 13 m 6y / M + - - + +++ +++ Remission [21]
 p.Ile810Asn £ 1 7 m / 8 m 20y / M ++ - + - +++ +++ Remission [35]
 p.Ser811Pro 2 1 m / 1 m 24y / F ++ + ++ ++ +++++ +++++ ++ [21, 31]
1 m / 1 m 20y / F ++ ++ + ++ ++++ - +
 p.Glu815Lys 22 1 m / 6 m (medians) Median 7.8y +++ ++ ++ +++ ++++ ++++ +++ [8, 2123, 31, 3335]
Cluster 4
 p.Leu839Pro 1 Neonatal 3 m / F NA NA NA ++ + ++++ - [31, 35]
 c.2542 + 1G > A 1 1 m / 10 m 26y / F ++ + - + + - +++ [21, 22, 31, 33]
p.Leu888Pro $ 1 1 m / 7 m 19y / M +++ - - ++ ++ ++ +++  
 p.Val919del 2 Unknown 3y / F +++ ++   + +++ +++ + [21, 31]
Neonatal / 5 m 17y / M ++ - - ++ ++++ ++++ -
 p.Asp923Asn 2 4 m / 29 m 7y / F - - + - +++ - - [34, 35, 40]
11 m / 24 m 4y / F + - - + ++ - -
 p.Cys927Phe 1 18 m / 18 m 15y / F ++ - + - Remission +++++ - [34]
p.Cys927Trp 1 4 m / 4 m 37y / M + - + + + Remission Remission  
Cluster 5
 p.Gly947Arg 15 3 m / 6 m (medians) Median 15y + - + + +++ +++ + [8, 21, 31, 3335]
 p.Glu951Lys 1 4 m / 10 m 20y / M ++ + +++ + Remission ++ -  
 p.Ala955Asp 1 Neonatal 4y / M +++ ++ - + +++++ ++++ ++ [21]
 p.Asp992Tyr 1 4 m / 8 m 32y / M + Unknown Unknown +++ +++ ++ + [21, 34]
  1. Novel mutations found in this study are given in bold characters. Of them, de novo mutations (both parents available and tested negative) are marked by the symbol $; Y: years, M: male, F: female, m: months; £: p.Ile810Asn (c.2429 T > A) corresponds to the Myshkin mice mutation; Remission, means no present at the last observation; First event: first paroxysmal event of the disease, either hemiplegic or other (i.e. abnormal ocular movements, double hemiplegia, tonic/dystonic attacks); Unknown: missed information; NA: not applicable because of young age at last observation. Reference sequences for corresponding ATP1A3 transcript and protein were [NM_152296.3] and [Uniprot P13637], respectively