ACR – Phelan-McDermid Syndrome

Evidence linking ACR (HGNC:126) to Phelan-McDermid syndrome (MONDO_0011652) comes exclusively from reports of contiguous gene deletions on 22q13.33. For example, a 9‑year‑old girl with PMS was found to harbor a de novo deletion including ACR among other genes (PMID:28289594). Similarly, an adult patient with atypical bipolar psychosis was shown to have a deletion affecting the first exon of ACR within the PMS region (PMID:30376408). In addition, a large multi‑patient study of 170 individuals demonstrated genotype–phenotype correlations in Class I deletions (which include ACR along with other critical genes such as SHANK3) (PMID:34559195).

Despite consistent identification of ACR within these deletion events, no isolated sequence variants specific to ACR have been reported in the context of PMS. Furthermore, while functional assessments of ACR exist, they have addressed its role in male infertility rather than neurodevelopment. Thus, the current genetic evidence is limited to observations in multi‑gene deletions rather than gene‑specific alterations. Key take‑home: Although ACR is recurrently deleted in PMS cases, its individual contribution remains uncertain, underscoring the need for further gene‑focused studies to determine its diagnostic utility.

References

• Balkan journal of medical genetics • 2016 • A 9-year‑old‑girl with Phelan McDermid Syndrome, who had been diagnosed with an autism spectrum disorder PMID:28289594
• Neurocase • 2018 • Phelan‑McDermid syndrome in adult patient with atypical bipolar psychosis repeatedly triggered by febrility PMID:30376408
• Human molecular genetics • 2022 • Strong evidence for genotype‑phenotype correlations in Phelan‑McDermid syndrome: results from the developmental synaptopathies consortium PMID:34559195

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