<unk>  is caused by a mutation in ZC4H2 on the X chromosome (Xq13-q21). There are five affected families, each with different mutations to the ZC4H2 gene. Family one has a substitution of Guanine (G) to a Cytosine (C) at basepair position 187. This leads to an amino acid change at position 63, where a leucine replaces a valine. This phenotype is the most mild because mutation only alters the secondary structure of the protein. This leads to a less stable protein that is still fully functional. Family two has a substitution of a Guanine (G) to a Adenine (A) at base pair position 593 which leads to an amino acid change from an arginine to glutamine. This phenotype is lethal at ages .5 to 8.0 years due to a change in the highly conserved zinc-finger domain which compromises the proteins function. Family three also has a lethal phenotype. Family three has a substitution of a Cytosine (C) to a Thiamine (T) as base pair position 601. This leads to an amino acid change at position 201 from a proline to serine. This phenotype is lethal from ages 1.4 weeks to 13.0 weeks because it alters the highly conserved domain of the protein which compromises its function. Families 4 and 5 have the same substitution of a Cytosine (C) to Thiamine (T) at base pair position 637. This leads to an amino acid change from Arginine to Tryptophan at amino acid position 213. This phenotype occurs near the highly conserved Carboxyl terminus of the protein. This leads to an intermediate phenotype, where females are normal except for a developmental which has been hypothesized to be caused by varying X-chromosome inactivation.
Wieacker syndrome
Nutcracker syndrome
Heyde's syndrome
Löffler's syndrome
Meigs's syndrome
Foerster's syndrome
Waltman Walter syndrome
Riddoch syndrome