Hydrocephalus

Gene: AP1S2

The mode of inheritance of this gene has been updated to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval.

Created: 31 Jan 2023, 5:24 p.m. | Last Modified: 31 Jan 2023, 5:24 p.m.

Panel Version: 3.5

Comment on mode of inheritance: Review of literature did not reveal any confirmed affected females. Female carriers of AP1S2 variants are phenotypically normal and have mostly shown random X-inactivation. Huo et al., 2019 (PMID: 30714330) state that they identified a female patient (I-1) but this individual was not available for genetic testing and so it is unclear whether they harboured a variant on a one or both alleles.

As it is not known definitively whether females require a variant on each allele of this gene in order to be affected, the MOI should be set to the default XL (i.e. monoallelic in females may cause disease).

Created: 18 Oct 2021, 11:49 a.m. | Last Modified: 12 Oct 2022, 2:52 p.m.

Panel Version: 2.132

I don't know

As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green

Created: 29 Jul 2019, 2:49 p.m. | Last Modified: 29 Jul 2019, 2:49 p.m.

Panel Version: 1.34

Green List (high evidence)

Several families with nonsense and splice mutations. Hydrocephalus reported but variable

Created: 9 May 2017, 1:22 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Mental retardation, X-linked syndromic 5

Publications

• 17186471