Table 2.

Females with mutations in the XDP disease-specific region or the TAF1 gene and their associated phenotypes. (For XDP, patients are listed in order of age of onset, whereas patients with congenital TAF1 mutations are listed in order of genetic changes (location of mutation along the amino acid sequence). For XDP, most cases are heterozygous (or presumed if not stated), whereas there is one case with homozygous XDP alleles as stated. For the cases with congenital TAF1 mutations, most mutations are missense mutations (described), whereas there is one case of frameshift mutation as stated.)

predicted genotype	genetic changes/X-inactivation status	clinical presentation	age of onset (years)	affected family members	reference
heterozygous XDP	3 XDP-specific mutant alleles at DXS8030, DXS8101, and DXS559	mild chorea	26 y	mother, maternal uncle, aunt, great-grandfather	[74]
heterozygous XDP	3 XDP-specific mutant alleles at DXS8030, DXS8101, and DXS559	parkinsonism: upper limb action and postural tremor, mild breakdown of limb rapid alternating movements (RAMs), mild retropulsion	35 y	1 brother	[74]
XDP	no data	leg cramps, face dystonia, generalized in 2 years	37 y	1 father, 2 brothers	[71]
heterozygous XDP	3 XDP-specific mutant alleles at DXS8030, DXS8101, and DXS559	perioral tremor, mild impairment of tandem gait	42 y	mother, 3 brothers	[74]
heterozygous XDP	3 XDP-specific mutant alleles at DXS8030, DXS8101, and DXS559	parkinsonism: breakdown of limb RAMs, shuffling gait, cervical dystonia	42 y	mother, 4 brothers	[74]
XDP	no data	leg dystonia, generalized within 4 years	47 y	1 sister	[71]
XDP	no data	slurred speech, gait problems, then dystonia with parkinsonism	48 y	uncles on both sides, brothers	[71]
XDP	no data	leg dystonia, generalized within 5 years, parkinsonism features after 16 years with dystonia	49 y	1 sister	[71]
heterozygous XDP	missense mutation DSC3 change (C>T) X-chromosome monosomy in a subset of cells	abnormal putamen and caudate, leg and hand dystonia, then parkinsonism with some dystonia Turner syndrome (short stature, drooping ears)	50 y	3 brothers, maternal grandfather, mother (?)	[71,73]
heterozygous XDP	3 XDP-specific mutant alleles at DXS8030, DXS8101, and DXS559	parkinsonism: shuffling gait, breakdown of limb RAMs, mild retropulsion leg chorea that generalized	51 y	maternal grandfather, 1 brother, 1 sister, 1 daughter	[113]
heterozygous XDP	5 disease-specific single-nucleotide changes 1 48 bp deletion 1 SVA retrotransposon insertion skewed X-inactivation (98:2%), only C>T expressed (no other changes)	parkinson symptoms caudate atrophy	57 y		[114]
XDP	no data	left foot dystonia	59 y		[113]
homozygous XDP	3 XDP-specific mutant alleles at DXS8030, DXS8101, and DXS559	parkinsonism: stooped posture, breakdown of RAMs of limbs, shuffling gait, retropulsion chorea in arm	72 y	2 sons	[74]
heterozygous XDP	3 XDP-specific mutant alleles at DXS8030, DXS8101, and DXS559	parkinsonism: shuffling gait, breakdown of limb RAMs, hypomimia, stooped posture, micrographia, absent arm swing bilaterally, tremor effects	75 y	1 daughter, 3 sons	[74]
heterozygous XDP	3 XDP-specific mutant alleles at DXS8030, DXS8101, and DXS559	parkinsonism: breakdown of RAMs, shuffling gait	75 y	1 daughter, 4 sons	[74]
heterozygous XDP	disease-specific haplotype SVA retrotransposon insertions	no neurological defects	NA	1 brother	[115]
heterozygous XDP	disease-specific haplotype SVA retrotransposon insertions	no neurological defects	NA	1 brother	[115]
heterozygous TAF1 mut	missense mutation (c.745G > A; p.Gly249Arg) skewed X-inactivation (95:5)	global developmental delay, delayed psychomotor development	12 mo	1 brother, mother, paternal grandmother with unidentified psychiatric pathology	[62]
heterozygous TAF1 mut	missense mutation (c.1786C > T; p.Pro596Ser)	no data	NA	3 sons	[3]
heterozygous de novo TAF1 mut	missense mutation (c.2039G > A p.Gly680Asp) skewed X-inactivation (> 90:10%)	dysmorphism in the face, hands, feet and neck, global developmental delay cardiovascular issues (heart murmur, pulmonary artery atresia and hypoplasia)	birth	none	[58]
de novo TAF1 mut	missense mutation (c.2039G > A; p.Gly680Asp)	congenital heart disease (pulmonary artery atresia)		none	[56]
TAF1 mut	missense mutation (g.23335G >T; exon18: c.2774G > A:p.G925D) assumed de novo (not confirmed)	at birth: jaundice, microcephaly, gastroesophageal reflux, hypotonia and congenital cardiopathy. during childhood: delayed developmental milestones, fine motor incoordination, delayed speech, moderate intellectual disability. Asthma, pneumonia dysmorphic features	birth	none confirmed	[116]
de novo TAF1 mut	missense mutation (c.2933C > T; p.Thr978Met)	congenital heart disease (Ebstein, ventricular septal defect (VSD), hypoplastic aortic arch)		none	[56]
heterozygous de novo TAF1 mut	missense mutation (c.3035C > T p.Thr1012Ile) skewed X-inactivation	learning disability, natal oral cleft, ventricular septal defect, swirling pigmentary disturbances, postnatal growth retardation, global developmental delay, generalized hypotonia, hypertelorism and other facial developmental abnormalities, sensorineural hearing impairment	birth	none	[58]
de novo TAF1 mut	missense mutation (c.3035C > T; pThr1012Ile)	congenital heart disease (VSD, PA stenosis)		none	[56]
heterozygous TAF1 mut	missense mutation (c.3568C > T; p.Arg1190Cys)	no symptoms	NA	2 sons	[117]
heterozygous TAF1 mut	frameshift mutation (c.3708A > G; p.(arg1228Ilefs*16) alternative transcript (splice site) with 28 bp deletion, resulting in a frameshift and a premature stop codon	no symptoms	NA	1 son	[3]
heterozygous TAF1 mut	missense mutation (c.4010T>C) skewed X-inactivation (99:1%)	no symptoms (healthy)	NA	2 sons	[3]