Table 1.

Overview of symptoms of individuals with NAE1 variants

NAE1 variant	Individual 1 c.[147G>C]; [254G>A]p.[Leu49Phe]; [Arg85Gln]	Individual 2c.[254G>A]; [254G>A]p.[Arg85Gln]; [Arg85Gln]	Individual 3 c.[1289 G>A]; [1289G>A] p.[Arg430Gln]; [Arg430Gln]	Individual 4 c.[882C>G]; [882C>G]p.[Cys294Trp]; [Cys294Trp]
Other variants identified with WES	full list in Table S1	no	no	SCN1A:c.[1624C>T]; [=], p.[Arg542∗]; [=],
Current age (years)	12	19	4	9
Gender	F	M	M	F
Pregnancy term (weeks)	40	36	37	40
Birth weight (g)	2,615 (−1.8 SDS)	2,767 (0.05 SDS)	2,140 (−1.6 SDS)	2,300 (−2.48 SDS)
Head circumference (cm)	51 (−0.47 SDS) (8 y)	54 (−0.59 SDS) (13 y)	47.3 (−1.5 SDS) (2 y 5 m)	48.7 (−1.73 SDS) (6 y 6 m)
Height (cm)	116 (−2.53 SDS) (8 y)	150 (−1.5 SDS) (13 y)	91 (−1 SDS) (2 y 5 m)	97 (−5.9 SDS) (7 y)
Cleft palate	–	+	–	–
Asymmetrical palate	+	+	–	N/A
Heart defects	+ ventricular septal defect and coarctation of the aorta	–	–	–
Developmental delay	severe	moderate	moderate	severe
Seizures	+	–	+	+
Hypotonia during infancy	+	–	+	+
Underdeveloped corpus callosum	+	+	+	+
Decreased myelination	+	+	+	+
Enlarged ventricles	+	–	+	+
Loss of milestones after infections	+	+	+	+
Neurodegeneration	+	+	+	+
Decreased bone density (DEXA scan)	+	+	+	+
Joint dislocation	+	+	–	–
Joint hyperextensibility	+	+	–	+
Joint stiffness	–	–	–	+
Resistant to sunburns	+	+	+	–
Recurrent infections	+ respiratory, urinary tract, skin	+ respiratory, skin	+ respiratory	+ respiratory, urinary tract
Hepatomegaly at infancy	+	–	+	–
Splenomegaly at infancy	+	+	+	–
Decreased amount of immunoglobulins	+ IgG	+ IgG, IgM	–	–
Leukopenia	+	+	–	+
Periodic lymphopenia	+	+	–	+
AST/ALT increase	+ during infections	–	–	–
Delayed closure of ischiopubic rami	+	+	N/A	N/A
Increased size of ischiopubic rami	+	+	+	+