Table 1.

Patient demographics, diagnostics, and results of targeted next Generation sequencing.

DBS ID	Subject ID	Birth State	Age at diagnosis (months)	Current age	Diagnostic work-up other than ATP7A sequencing	ATP7A Transcript/protein variant detected on diagnostic work-up	ATP7ATranscript/protein variant detected on blinded tNGS	Chromosomal Position/dbSNP [Hg19]
1	A	VA	14	5y, 3 m	Multiple EEGs, brain MRI, serum Cu & Cp, plasma catechols	c.2357 T > G; p.Met786Arga	c.2357 T > G/ p.Met786Arg	ChrX:77268560/ rs797045354
2	B	MA	8.5	5y, 4 m	Brain MRI, plasma catechols	dupl exon 7-12b	dupl exon 7–12
3	C	TX	5	3y, 5 m	EEG, brain MRI	del exons 7-23c	del exons 7–23
4	D	AZ	2.5	3y	EEG, brain MRI, plasma catechols	Not performed (no insurance)	del exon 13–14
5	E	CA	14	3y, 2 m	EEG, brain MRI, serum Cu & Cp, plasma catechols	c.2172 + 6 T > G; (c.IVS9 + 6 T > G)d	c.2172 + 6 T > G (c.IVS9 + 6 T > G)/ n.a.	chrX:77267177/ n.a.
6	B	MA	8.5	5y, 4 m	Brain MRI, plasma catechols	dupl exon 7-12b	dupl exon 7–12
7	F	IL	48	7y, 4 m	Muscle biopsy, serum Cu&Cp, chromosome microarray, plasma amino acids, urine organic acids, brain MRI/MRS; skin biopsy	c.3014 G > T; p.Gly1005Vale	c.3014G > T/ p.Gly1005Val	ChrX:77284844/ n.a.
8	G	UT	0.5⁎	1y, 9 m	Plasma catechols	Not performed (Known family variant [16])	del exon 13–14
9	H	MI	4	3y, 4 m	Brain and abdomen MRI/MRA	c.2129_2132 del4f p.Ser710LeufsTer2	c.2129_2132delCTGT/ p.Ser710LeufsTer2	chrX: 77267128–77,267,131/ n.a.
10	I	AL	9	2y, 5 m	Karyotype, CNV microarray, Fragile X	Inconclusive resultsd, g	Partial exon 12 del starts at c.2614, ends in IVS12
11	J	GA	9	5y	Brain MRI/MRS, CT head, lysosomal enzyme screen, metabolic LP, chromosomal microarray, dilated eye exam, serum Cu & Cp, amino acids, pyruvate, fatty acid profile, CBC, plasma catechols, urine MPS screen, s-sulfocysteine, oligosaccharides, n-acetyl-aspartic acid and organic acids	None detectedc	None detected/ n.a	n.a./n.a.
12	K	MA	12	3y, 2 m	Neurological workup, cardiac echo, EKG, EEG, video EEG, cranial ultrasound, brain MRI, plasma catechols, SNP microarray, epilepsy gene panel, PT/OT, blood: folate, vitamin B12, ferritin, thyroid panel, prealbumin, CPK	c.1139_1140delTGd p.Val380AspfsTer4	c.1139_1140delTG/ p.Val380AspfsTer4	chrX:77245255–77,245,256/ n.a.
13	L	AL	2.5	Died at 13 m	Head ultrasound, cardiac echo, upper GI, urine creatinine, serum Cu & Cp, CBC, electrolytes, developmental and speech therapy assessments	c.601C > T p.Arg201Terb	c.601C > T/ p.Arg201Ter	chrX: 77244218/ rs151340633
14	M	OK	7	2y, 1 m	Brain MRI, serum Cu & Cp, plasma catechols, CBC, CPK, fatty acid, amino acid and acylcarnitine profiles, comprehensive metabolic panel	c.3526C>Th p.Gln1176Ter	c.3526C > T/ p.Gln1176Ter	chrX: 77294348/ n.a.
15	NormalControl	–	–	–	–	–	None detected/n.a	n.a./n.a.
16	N	NY	0.3⁎	1y, 6 m	Prenatal molecular analysis	exon 1 (5’ UTR) deli	exon 1 (5’ UTR) del
17	O	LA	1.5	4y, 8 m	Plasma catechols	c.2627-1G > A (c.IVS12-1G > A)b	c.2627-1G > A (c.IVS12-1G > A)/ n.a.	chrX:77275740/n.a.
18	P	FL	0.25 ⁎	2y, 3 m	Plasma catechols	exon 1 (5’ UTR) del j	exon1 (5’ UTR) del
19	Q	CO	11	2y, 11 m	EEG, skull x-ray, brain MRI, VCUG, serum Cu & Cp	c.4117G>Ck p.Ala1373Pro	c.4117G > C/ p.Ala1373Pro	chrX:77298926/ n.a.
20	R	PA	5	1y, 8 m	EEG, serum Cu & Cp, plasma catechols	c.3445C>Ta p.Gln1149Ter	c.3445C > T/ p.Gln1149Ter	chrX:77289253/n.a.
21	S	MA	7	3y, 2 m	Plasma catechols	c.3071 T>Ab p.Ile1024Lys	c.3071 T > A/ p.Ile1024Lys	chrX:77284901/ rs797044648
22	T	AZ	9.5	Died at 2y, 5 m	EEG	c.3496dupAd p.Ile1316AsnfsTer12	c.3946dupA/ p.Ile1316AsnfsTer12	chrX:77298226/ n.a.
23	U	CA	2	1y,1 m	Plasma catechols	c.4006-1G>Al (c.IVS20-1G > A)	c.4006-1G > A (c.IVS20-1G > A)/ n.a.	chrX:77298814/n.a.
24	V	TN	7	4y,10 m	EEG, brain MRI, brain and internal auditory canal CT scans, skeletal survey, chest x-ray, serum Cu & Cp, karyotype, microarray, hearing and ophthalmology evaluations, abdominal ultrasound and radiograph, EKG	c.3753delTc p.Leu1252Ter	c.3753delT/ p.Leu1252Ter	chrX:77296182/n.a.

ATM = ataxia telangienctasia; Cp = ceruloplasmin; CT = computerized tomography; Cu = copper; EEG = electroencephalogram, EKG = electrocardiogram; MRA = magnetic resonance angiography; MRI = magnetic resonance imaging; MRS = magnetic resonance spectroscopy; NCV = nerve conduction velocity; OT = occupational therapy; PT = physical therapy; SNP = single nucleotide polymorphism; VCUG = voiding cystourethrogram.

^⁎Screened early due to known 50% risk (positive family history).

^aPrevention Genetics.

^bEmory Genetics Laboratory.

^cBaylor Medical Genetics Laboratories.

^dARUP Laboratories.

^eGene Dx.

^_fConnective Tissue Gene Tests.

^gQuest Diagnostics.

^hFulgent Diagnostics.

ⁱUniversity of Chicago.

^jGeneCare Medical Genetics Center (prenatal analysis of subject's older affected brother).

^kBaylor Miraca.

^lInvitae.