Table 1.

Genotype—phenotype correlations

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, 33–35]
		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, 21–23, 31, 33–35]
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, 21–23, 31, 33–35]
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, 33–35]
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]

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