ClinGen Dosage Sensitivity Curation Page

IL1RAPL1

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
22031302 Mikhail et al. (2011) report a male with global developmental delays, intellectual disability, and dysmorphic facial features who had a 1.07 Mb intragenic deletion of 5 exons that was inherited from a normal mother.
21933724 Youngs et al. (2012) report a 15-year old male with autism, mild intellectual disability, hyperopia, hyperactivity, self-injurious and aggressive behavior, and dysmorphic features who had a 950 kb intragenic deletion. This was inherited from his mother, who had a history of some learning difficulties, and was also found in his maternal half-brother who has intellectual disability and similar facial features. Other family members (both male and female) were reported to have similar facial features and intellectual disability but were not available for testing.
21271657 Behnecke et al (2011) report a male patient with intellectual disability, global delays, dysmorphic features, scoliosis, and strabismus who had a de novo 300 kb intragenic deletion of exon 2. They also report a male proband with intellectual disability, global delays, dysmorphic features, astigmatism, and strabismus who had a maternally inherited 482 kb deletion of exons 3-5. His mother had learning difficulties and similar eye problems. A carrier maternal aunt had learning difficulties and her son with the deletion was reported to be physically and developmentally similar to the proband.

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.

Evidence for Triplosenstive Phenotype

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.

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.