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ADCY5 – Neurodevelopmental Disorder

Heterozygous microdeletion 3q13.33–3q21.2 encompassing ADCY5 was identified by chromosomal microarray in two related individuals from a seven-member pedigree presenting with neurodevelopmental disorder (2 probands)(PMID:39502849). Affected individuals exhibited attention deficit hyperactivity disorder, short stature, intellectual disability, concurrent epilepsy, and dilated left third ventricle (HP:0007018, HP:0004322, HP:0001249).

Next-generation sequencing excluded secondary allelic mutations within the deleted region, implicating haploinsufficiency of one or more genes—ADCY5, SEMA5B, KPNA1, or CASR—in the pathogenesis. No unrelated cases or dedicated functional assays evaluating ADCY5 dosage in neurodevelopment have been reported, leaving the specific contribution of ADCY5 unresolved. Key Take-home: Further unrelated case reports and functional studies are needed to clarify the role of ADCY5 haploinsufficiency in neurodevelopmental disorder.

References

  • Journal of pediatric genetics • 2024 • Microdeletion 3q13.33-3q21.2: A Rare Cause of Neurodevelopmental Disorder. PMID:39502849

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Single family with 2 probands and no unrelated cases limits evidence to a single pedigree (2 probands)(PMID:39502849)

Genetic Evidence

Limited

Microdeletion segregates in one family (2 probands, 1 additional affected relative)(PMID:39502849)

Functional Evidence

No evidence

No functional assays directly assess ADCY5 haploinsufficiency in neurodevelopmental disorder