Intellectual disability syndromic and non-syndromic
Gene: AMER1

AMER1 (APC membrane recruitment protein 1)
EnsemblGeneIds (GRCh38): ENSG00000184675
EnsemblGeneIds (GRCh37): ENSG00000184675
OMIM: 300647, Gene2Phenotype
AMER1 is in 10 panels

1 review

Deepak Subramanian (Peter MacCallum Cancer Centre)

Green List (high evidence)

Osteopathia striata with cranial sclerosis (OS-CS) is a bone dysplasia characterized by longitudinal striations of the metaphyses of the long bones, sclerosis of the craniofacial bones, macrocephaly, cleft palate and hearing loss, as well as other organ malformations, particularly in affected males (ORPHA:2780). It is associated with X-linked monoallelic loss-of-function (LoF) variants in AMER1/WTX, displaying full penetrance and variable expressivity in both affected heterozygous females and hemizygous males, with the latter exhibiting a broad phenotypic spectrum from mild to severe with foetal/neonatal lethality (Gear and Savarirayan, GeneReviews, 2021). Intellectual disability (ID) has been reported in multiple (>3) individuals with the disorder (see cited publications); in all reviewed cases, other syndromic features of the disease were also present. Around 30% of affected females are estimated to have mild ID, although at least one female with severe ID has been reported (PMID 19079258). Surviving affected males are more likely to have ID, with around 80% estimated to have mild-to-moderate ID (PMID 22043478, 20950377, 22987541, 28497491). No non-syndromic ID cases with LoF variants in AMER1 have been reported to date in the literature.
Created: 5 Dec 2022, 5:14 p.m. | Last Modified: 5 Dec 2022, 5:14 p.m.

Panel Version: 0.5079

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Osteopathia striata with cranial sclerosis, OMIM:300373; Osteopathia striata-cranial sclerosis syndrome, ORPHA:2780; Intellectual disability, HP:0001249

Publications

Created: 5 Dec 2022, 5:14 p.m.
Last Modified: 5 Dec 2022, 5:14 p.m.
Panel version: 0.5079

Details

Mode of Inheritance

X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Sources

Expert Review Green
Genetic Health Queensland

Phenotypes

Osteopathia striata with cranial sclerosis, OMIM:300373

OMIM

300647

Clinvar variants

Variants in AMER1

Penetrance

None

Publications

Panels with this gene