375: Biallelic DSCAM LoF: a syndromic NDD with nystagmus and cone-pathway retinal dysfunction

Douzgou Houge S et al., Human Genetics and Genomics Advances - This paper reports six individuals with biallelic loss-of-function DSCAM variants, delineating a recessive syndrome of moderate-to-severe neurodevelopmental delay with poor language, early focal seizures, hypotonia, short stature, and characteristic rotatory/vertical nystagmus with cone-pathway retinal dysfunction. Key terms: DSCAM, neurodevelopmental delay, nystagmus, retinal dysfunction, electroretinography.

Study Highlights:
The authors describe six patients (including four newly reported) with homozygous or compound heterozygous predicted loss-of-function variants in DSCAM. All individuals share moderate-to-severe neurodevelopmental delay, impaired language, frequent hypotonia, and short stature, with focal seizures in some. A consistent ophthalmic phenotype of rotatory/vertical nystagmus and poor vision was observed, and ERG in two patients showed relative rod preservation but marked cone-pathway dysfunction, implicating cone-associated bipolar cells. The clinical and electrophysiological findings align with animal models showing disrupted retinal lamination and mosaic spacing caused by loss of DSCAM.

Conclusion:
Biallelic DSCAM loss-of-function defines a rare recessive neurodevelopmental syndrome characterized by motor and cognitive impairment and a distinctive, developmentally origin retinal dysfunction primarily affecting the cone pathway detectable by ERG.

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Article title:
Biallelic loss-of-function variants in DSCAM cause a neurodevelopmental syndrome with nystagmus and retinal dysfunction

First author:
Douzgou Houge S

Journal:
Human Genetics and Genomics Advances

DOI:
10.1016/j.xhgg.2026.100622

Reference:
Douzgou Houge S., Bredrup C., Wivestad Jansson R., Bojovic O., Aljamal B.M., Al-Otaibi M., Plomp A.S., Motazacker M.M., van Genderen M.M., Mellgren A., Alkuraya H., Hikmat O., Haukanes B.I., Alkuraya F.S., Douzgos Houge G. Biallelic loss-of-function variants in DSCAM cause a neurodevelopmental syndrome with nystagmus and retinal dysfunction. Human Genetics and Genomics Advances 7, 100622 (July 9, 2026). https://doi.org/10.1016/j.xhgg.2026.100622.

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-05-26.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: The transcript covers the study’s core claims: DSCAM function and retinal organization, genetic evidence for biallelic LoF variants, the neurodevelopmental phenotype, ERG findings showing cone pathway impairment with rod preservation, animal-model context, consanguinity patterns, and ASD-related discussions.
- transcript topics: DSCAM role in retinal self-avoidance and patterning; Genetic identification of DSCAM LoF variants via trio exome sequencing; Clinical phenotype: neurodevelopmental delay, language impairment, seizures, hypotonia, short stature; Ophthalmic phenotype and ERG-based retinal function (cone vs rod); Cone-associated bipolar cells in the retina as the site of dysfunction; Animal-model evidence (chicken retina and DSCAM KO mice) for retinal organization

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 6
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Six individuals with biallelic DSCAM loss-of-function variants described in the study
- Cone-pathway dysfunction with preserved rod-pathway function demonstrated by ERG in some individuals
- Cone-associated bipolar cells implicated as the site of dysfunction in the retina
- DSCAM is required for self-neuronal avoidance; animal models show retinal disorganization when DSCAM is disrupted
- Consanguineous parental relationships and twin pairs observed in the cohort
- Monoallelic DSCAM variants have been associated with autism in separate studies

QC result: Pass.