Table 1.

Genotype and clinical features of patients with HSPD1 and HSPE1 variations

Disease association	Variations in HSPD1 or HSPE1	Genotype	Age at onset	Gender	Symptoms	PolyPhen-2 predictiona	Growth in genetic complementation assay	ACADS polymorphism genotype	Urine ethylmalonic acid	Reference(s)
Hypomyelinating leukodystrophy 4 (HLD4;MitCHAP60; MIM 612233)	p.Asp29Gly c.[86A > G]	Homozygous	3 mo	M	Progressive hypertonia and hyperreflexia, intermittent nystagmus, lack of head control, psychomotor developmental delay, no language, decreased social contact, progressive limb spasticity	Benign	Slow, temperature-sensitive	c.[625G > A]; [625G > A]	Elevated	Magen et al. 2008; Kusk et al. 2016; Parnas et al. 2009
Hereditary spastic paraplegia (SPG13; MIM 605280)	p.Val98Ile c.[292G > A]	Heterozygous	40 yr	F	Severe functional handicaps, weakness of the lower limbs, retinopathy, ataxia, and mental retardation	Possibly damaging	No growth	c.[625G > A]; [625=]	N/A	Hansen et al. 2002
Neurological and developmental disorder	HSP10:p.Leu73Phe c.[217C > T]	Heterozygous (de novo)	3 mo	M	Infantile spasms, hypotonia, developmental delay, a slightly enlarged liver, nystagmus, macrocephaly	Possibly damaging	N/A	c.[625=]; [625=]	Normal	Bie et al. 2016
Hypomyelination	p.Leu47Val c.[139T > G]	Heterozygous (de novo)	18 mo	M	Diffuse hypomyelination, gait instability, mild ataxia, dysmature motor coordination	Probably damaging	No growth	c.[625G > A]; [625=]	Elevated	Yamamoto et al. 2018

(M) Male, (F) female, (N/A) not available.

^aPolyPhen-2 has three levels of damage prediction, from most damaging to the least: probably damaging, possibly damaging, and benign.