Novel TMEM63A mutation associated with transient hypomyelination of infancy - lessons from a previously negative whole-exome sequencing case: Three case reports

Table 1 Clinical and genetic characteristics of individuals with TMEM63A variants: Present series and published cases

Individual	Present series			Yan et al[6], 2019				Tonduti et al[7], 2021	Fukumura et al[8], 2022	Gerik-Celebi et al[9], 2023	Siori et al[10], 2024
	Case 1 (III-2)	Case 2 (III-3)	Case 3 (III-4)	Case 1	Case 2	Case 3	Case 4
Sex	Female	Female	Male	Male	Male	Female	Male	Female	Female	Female	Male
Ethnicity	Asian	Asian	Asian	Caucasian	Caucasian	Asian	Asian	Caucasian	Asian	Caucasian	Caucasian
TMEM63A variant (NM_014698.3)	c.146G>T, p.Gly49Val	c.146G>T, p.Gly49Val	c.146G>T, p.Gly49Val	c.1699G>A, p.Gly567Ser	c.1699G>A, p.Gly567Ser	c.1385T>A, p.Ile462Asn	c.503G>A, p.Gly168Glu	c.1675T>C, p.Tyr559His	c.1658G>T, p.Gly553Val	c.33-2A>G, p.?	c.220A>T, p.Arg74*
Inheritance	Maternal	Maternal	Maternal	De novo	Paternal	De novo	De novo	De novo	De novo	Paternal	Paternal
Age at symptom onset	2 weeks	20 days	2 months	2 weeks	1 day	10 days	1 day	1 day	1 day	NA	NA
Nystagmus	+	+	+	+	+	+	+	+	+	+	NA
Resolved at	24 months	15 months	8 months	5 years	7 years	12 months	14 months	NA	NA	NA	NA
Head titubation	+	+	+	+	+	+	+	+	+	NA	NA
Hypotonia	+	+	+	+	+	+	+	+	+	+	+
Ataxia	+	-	-	+	+	-	-	NA	NA	NA	NA
Developmental delay	Age-appropriate	Age-appropriate	Age-appropriate	Age-appropriate	Slight language delay	Age-appropriate	Language delay	Delay at last visit (13 months)	Severe delay	Delay	Delay
Other comorbidities	Esotropia	Esotropia	-	Optic atrophy, myopia, Crohn disease	Seizure, LD, mild myopia, PDA, hypospadias	-	Myopia	Paroxysmal eyelid twitching, spinal cord involvement	Seizure	Dysmorphic facial feature	Dysmorphic facial feature
Motor milestones
Head control	5 months	6 months	5 months	NA	NA	NA	10 months	13 months	Unable	NA	6 months
Sit alone	12 months	11 months	9 months	12 months	NA	NA	16 months	NA	Unable	NA	10 months
Walk alone	17 months	16 months	14 months	20 months	17 months	26 months	36 months	NA	Unable	NA	18 months
Neurophysiological findings	Abnormal ABR/ASSR at 4 months	Normal ABR/ASSR at 1 year	NA	-	Abnormal BAEP, VEP	-	Abnormal BAEP, VEP	Abnormal VEP	Abnormal BAEP	-	-

Data are presented for all individuals with confirmed TMEM63A variants reported in the literature. Plus sign (+) indicates feature present; em dash (-) indicates feature absent or not reported. Motor milestones represent age at achievement. Neurophysiological findings were obtained at varying ages across studies. ABR: Auditory brainstem response; ASSR: Auditory steady-state response; BAEP: Brainstem auditory evoked potential; LD: Learning disability; NA: Not available; PDA: Patent ductus arteriosus; VEP: Visual evoked potential.