Table 1.

Characteristics of Individuals with Biallelic Variants in TBCK

	Affected Individuals
1-1a	1-2a	2-1	3-1	4-1	4-2	5-1	6-1	6-2	7-1	8-1	9-1	9-2
Variants (GenBank: NM_001163435.2)	Hom c.1897+1G>A	Hom c.1897+1G>A	Hom c.831_832insTA (p.Pro278Tyrfs∗18)	Hom c.1652T>C (p.Leu551Pro)	Het c.[2060−2A>G];[803_806delTGAA], p.[=];[Met268fsArg∗26]	Het c.[2060−2A>G];[803_806delTGAA], p.[=];[Met268fsArg∗26]	Hom c.376C>T (p.Arg126∗)	Hom c.1370delA (p.Asn457Thrfs∗15)	Hom c.1370delA (p.Asn457Thrfs∗15)	Hom c.455+4 C>G	Hom c.376C>T (p.Arg126∗)	Het c.[(658+1_ 659−1)_(2059+1_2060−1)del];[376C>T], p[=];[Arg126∗]	Het c.[(658+1_ 659−1)_(2059+1_2060−1)del];[376C>T], p[=];[Arg126∗]
Mutation type	splice site and frameshift	splice site and frameshift	insertion and frameshift	missense	splice site and frameshift; frameshift	splice site and frameshift; frameshift	nonsense	frameshift	frameshift	splice, skipping of exons 3 and 4	nonsense	deletion of exons 7–22; nonsense	deletion of exons 7–22; nonsense
Consanguinity reported	+	+	−	+	−	−	+	+	+	+	−	−	−
Age at last exam	died at 5 years	11 years	5 years	11 years	4 years	2 years	10 years	12 years	3 years	6 years	12 years	10 years	2 years
Sex	male	female	male	male	female	female	female	male	female	male	female	female	male
Ethnicity	Saudi	Saudi	Syrian	Pakistani	mixed European	mixed European	Hispanic	Algerian	Algerian	Palestinian	Puerto Rican and Dominican	Puerto Rican and Mexican	Puerto Rican and Mexican
Prenatal findings	decreased fetal movement, oligohydramnios	none reported	premature contractions	none reported	ventriculomegaly	none reported	none reported	none reported	none reported	none reported	none reported	renal pyelectasis and hepatic calcifications	none reported
Development
Motor	no sitting	rolling at 11 years	no sitting	mild delay	independent walking	sitting	severe delay	sitting	walking at 2.5 years	sitting	sitting	no sitting	no sitting
Speech	few words	babbling, no words	non-verbal	mild delay	few single words	many words	no words	no words	few words	few words	no words	non-verbal	non-verbal
Cognitive	severe delay	severe delay	severe delay	mild delay	severe delay	mild delay	severe delay	severe delay	moderate delay	severe delay	severe delay	severe delay	severe delay
Regression	−	−	−	−	−	−	+	−	−	−	−	−	−
Ventilator dependence	−	−	tracheostomy only	−	−	−	+	−	−	−	tracheostomy only	−	−
MRI findings	diffuse brain atrophy, abnormal white-matter signal intensity	diffuse brain atrophy	posterior thinning of the corpus callosum and brainstem, ex vacuo dilation of the ventricles, periventricular leukomalacia	mild prominence of the lateral ventricles	none reported	none reported	central and cortical volume loss with atrophy	discrete abnormalities of the periventricular and bilateral parietal white matter	discrete abnormalities of the periventricular and bilateral parietal white matter	discrete abnormalities of the periventricular and bilateral parietal white matter	abnormal white-matter intensities	bilateral frontal white-matter hyperintensities on T2-weighted FLAIR	overall paucity of white matter, mild hyperintensity and central volume loss on T2-weighted FLAIR
Hypotonia	severe	severe	severe	mild to moderate	moderate	severe	severe	moderate	moderate	severe	severe	progressively severe	progressively severe
Reflexes	delayed	reduced	absent in lower extremities	normal	reduced	reduced	globally decreased	present	present	absent in lower extremities	reduced	not reported	not reported
Seizures	+	+	+	−	−	−	+	−	−	−	+	−	−
Unusual facial features	sloped forehead, bulbous nose, tented upper lip, upward slant of palpebral fissures	tented upper lip, sloped forehead, bulbous nose	macrocephaly	epicanthal folds, broad nasal bridge, deep-set eyes	−	−	mildly coarse facies, synophrys, long eyelashes, macroglossia, microcephaly, hirsuitism	wide forehead, bulbous nose, open mouth, thick lips, deep palate, prognathic mandible	macrocephaly, wide forehead, short neck	−	macrocephaly, very coarse facial features, bushy eyebrows, macroglossia	metopic ridge, thick bushy eyebrows, mildly high-arched palate	mildly coarse facial features, hirsute, epicanthal folds, long philtrum, tented upper lip
Other findings	abnormal eye movements, asthma, eczema	hypothyroidism, pernicious anemia, recurrent candidiasis	strabismus, nystagmus	autism, bipolar disorder, high-arched palate, broad fingers and toes, mild scoliosis	mild macrocephaly	−	corneal clouding, central adrenal insufficiency and growth hormone deficiency, scoliosis	hearing loss, behavioral difficulties, delayed bone age	delayed bone age	pectus excavatum, pulmonic stenosis	possible mitochondrial complex III deficiency, severe scoliosis, neurogenic bladder, hyperthyroidism	small pectus excavatum, mild scoliosis, diastasis recti, clinodactyly, partial syndactyly of toes 2 and 3	cryptorchidism, 11 rib pairs, resolved pelviectasis

Abbreviations are as follows: Hom, homozygous; and Het, heterozygous.

^aThese individuals were previously reported by Alazami et al.³