No evidence for preferential X-chromosome inactivation as the main cause of divergent phenotypes in sisters with X-linked hypohidrotic ectodermal dysplasia

Table 5 EDA genotypes of affected individuals and X-chromosome inactivation patterns

Code	EDA variant	Changes at the amino acid level	Predicted effect	XI ratios in % (A1:A2)*	Classification
F1_S1	c.64_71dup8	p.Cys25AlafsX35	Truncated, dysfunctional protein, possibly causing NMD	51:49	Random
F1_S2	c.64_71dup8	p.Cys25AlafsX35	Truncated, dysfunctional protein, possibly causing NMD	54:46	Random
F1_M	c.64_71dup8	p.Cys25AlafsX35	Truncated, dysfunctional protein, possibly causing NMD	47:53	Random
F2_S1	c.917A>G	p.Gln306Arg	Impaired receptor binding	37:63	Random
F2_S2	c.917A>G	p.Gln306Arg	Impaired receptor binding	51:49	Random
F2_M	c.917A>G	p.Gln306Arg	Impaired receptor binding	64:36	Random
F3_S1	c.871G>A	p.Gly291Arg	Impaired receptor binding	31:69	Moderately skewed
F3_S2	c.871G>A	p.Gly291Arg	Impaired receptor binding	65:35	Random
F3_F	c.871G>A	p.Gly291Arg	Impaired receptor binding	/	/
F4_S1	c.467G>A	p.Arg156His	Abolished furin cleavage	46:54	Random
F4_S2	c.467G>A	p.Arg156His	Abolished furin cleavage	39:61	Random
F4_M	c.467G>A	p.Arg156His	Abolished furin cleavage	30:70	Moderately skewed
F5_S1	c.1045G>A	p.Ala349Thr	Impaired receptor binding	76:24	Moderately skewed
F5_S2	c.1045G>A	p.Ala349Thr	Impaired receptor binding	61:39	Random
F5_F	c.1045G>A	p.Ala349Thr	Impaired receptor binding	/	/
F6_S1	c.1133C>T	p.Thr378Met	Impaired receptor binding	81:19	Highly skewed
F6_S2	c.1133C>T	p.Thr378Met	Impaired receptor binding	71:29	Moderately skewed
F6_M	c.1133C>T	p.Thr378Met	Impaired receptor binding	54:46	Random

Abbreviations: F, family; S, sister; M, mother; NMD, nonsense-mediated decay; A1, allele 1 (the shorter allele); A2, allele 2 (the longer allele); *rounded mean values of the experiments using HpaII and CfoI, respectively; bold values mark the alleles with the disease-causing EDA variant

ISSN: 1750-1172