ZDHHC9

• Haploinsufficiency score: 2
• Strength of Evidence (disclaimer): Some evidence for dosage pathogenicity
• Haploinsufficiency Phenotype: MENTAL RETARDATION, X-LINKED, SYNDROMIC, RAYMOND TYPE; MRXSR

Evidence for haploinsufficiency phenotype

PubMed ID	Description
17436253	Raymond (2007): Description of four families with X-linked mental retardation, three of which also had Marfanoid habitus, who had mutations identified in ZDHHC9 (also reported in Tarpy et al, PMID: 19377476). One mutations is a frameshift, one is IVS3+5 G>C which is predicted to result in a truncated protein confirmed by RNA studies, and two are missense. Female carriers were unaffected.

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

• Triplosensitivity score: 0
• Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.