TABLE 1.

Summary of human disease-causing ELOVL4 mutations.

Human disease	Inheritance	Genomic mutation	Protein mutation/structure/function	Retinal symptoms	Other CNS symptoms	Skin symptoms	Onset/Progression	References
Wildtype ELOVL4.	Homozygous	Wildtype (no mutation)	Wildtype. Intrinsic endoplasmic reticulum membrane protein. 314 AA length	–	–	–	–	Edwards et al., 2001; Zhang et al., 2001
Stargardt’s-like macular dystrophy (STGD3)	Autosomal dominant	790–794 del AACTT “5 bp deletion”	Exon 6, N264Lfs10X	Macular degeneration	None reported	None	Juvenile onset. Rapid progression.	Edwards et al., 2001; Zhang et al., 2001
Stargardt’s-like macular dystrophy (STGD3)	Autosomal dominant	789 del T plus 794 del T “2 bp deletion”	Exon 6, N264Tfs9X	Macular degeneration	None reported	None	Juvenile onset. Rapid progression.	Bernstein et al., 2001
Stargardt’s-like macular dystrophy (STGD3)	Autosomal dominant	c.810C > G	Exon 6, Y270X	Macular degeneration	None reported	None	Juvenile onset. Rapid progression.	Maugeri et al., 2004
Stargardt’s-like macular dystrophy (STGD3)	Autosomal dominant	c.814G > C	Exon 6, E272Q	Macular degeneration	None reported	None reported	Juvenile onset. Rapid progression.	Bardak et al., 2016
Stargardt’s-like macular dystrophy (STGD3)	Autosomal dominant	c.895A > G	Exon 6, M299V	Macular degeneration	None reported	None reported	Juvenile onset. Rapid progression.	Bardak et al., 2016
Stargardt’s-like macular dystrophy (STGD3)	Autosomal dominant	c.-90 G > C	Promoter, rs62407622	Macular degeneration	None reported	None reported	Juvenile onset. Rapid progression.	Donato et al., 2018
Stargardt’s-like macular dystrophy (STGD3)	Autosomal dominant	c.-236 C > T	Promoter, rs240307	Macular degeneration	None reported	None reported	Juvenile onset. Rapid progression.	Donato et al., 2018
Spinocerebellar ataxia (SCA34)	Autosomal dominant	c.504G > C	Exon 4, L168F Full-length protein	Not reported	Gait and limb ataxia. Dysarthria. Nystagmus and eye movement deficits. Abnormal tendon reflexes. No autonomic disturbance. Cerebellar and pontine atrophy.	Erythrokerato-dermia Variabilis	Avg. onset: 51 years of age. Onset in 4th to 5th decade. Slow progression.	Cadieux-Dion et al., 2014
Spinocerebellar ataxia (SCA34)	Autosomal dominant	c.736T > G	Exon 4, W246G Full-length protein	Normal	Gait and limb ataxia. Dysarthria. Nystagmus and eye movement deficits. Abnormal tendon reflexes. Babinski reflex may be present. Autonomic disturbance sometimes present. Cerebellar and pontine atrophy.	None	Avg. onset: 34 years of age (range: 2nd–6th decade). Slow progression.	Ozaki et al., 2015
Spinocerebellar ataxia (SCA34)	Autosomal dominant	c.539A > C	Exon 4, Q180P Full length protein	None reported	Gait ataxia more pronounced than limb ataxia. Dysarthria. Nystagmus and eye movement deficits. Moderate cerebellar and pontine atrophy.	Erythrokerato-dermia Variabilis	Onset in middle 20 s (1 case known). Progression unclear at present	Bourassa et al., 2015
Spinocerebellar ataxia (SCA34)	Autosomal dominant	c698C > T	Exon 4, T233M Full length protein	None reported	Gait ataxia (no limb ataxia). No dysarthria. No nystagmus, but abnormal eye movements present. Hyporeflexia. Mild cerebellar and pontine atrophy.	Erythrokerato-dermia Variabilis	15 years of age (1 case known). Slow progression	Bourque et al., 2018
ELOVL4 Neuro-ichthyotic syndrome	Homozygous recessive	c.689delT	Exon 6, I230MfsX22	Normal fundus and flicker ERG	Seizures, intellectual disability, spastic quadriplegia	Ichthyosis	Infancy (Gestation?) Developmental delay	Aldahmesh et al., 2011
ELOVL4 Neuro-ichthyotic syndrome	Homozygous recessive	c.646C > T	Exon 5, R216X	Not reported	Seizures, intellectual disability, spastic quadriplegia	Ichthyosis	Infancy (Gestation?) Developmental delay	Aldahmesh et al., 2011
ELOVL4 Neuro-ichthyotic syndrome	Homozygous recessive	c.78C > G	Exon 1, Y26X	Not reported	Seizures, intellectual disability, spastic quadriplegia	Ichthyosis	Infancy (Gestation?) Developmental delay	Mir et al., 2014