AHDC1AT-hook DNA binding motif containing 1

SFARI Gene score

Mutations in the AHDC1 gene were found in four individuals presenting with a syndrome characterized by intellectual disability, expressive language delay, hypotonia, and obstructive sleep apnea, which was subsequently classified as Xia-Gibbs syndrome (OMIM 615829), (Xia et al., 2014). One of the original subjects from the Xia et al., 2014 study (subject 4) is described as having "noncommunicating autism" as a clinical feature in Table 1. Novel de novo variants in the AHDC1 gene (one frameshift, one missense variant predicted to be benign) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Exome sequencing of 2157 cases with intellectual disability or developmental delay in Yang et al., 2016 identified seven proband-patient trios with de novo AHDC1 variants; probands typically presented with developmental delay, intellectual disability, absent or limited speech, hypotonia, dysmorphic features, brain abnormalities, failure to thrive/feeding difficulties, and ataxia/gait abnormalities, and two of the seven probands were additionally diagnosed with autism based on DSM-IV or DSM-V criteria.

criteria met

See SFARI Gene'scoring criteria

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

04-01-2017