OtherMolecular autism2018

Modeling the neuropsychiatric manifestations of Lowe syndrome using induced pluripotent stem cells: defective F-actin polymerization and WAVE-1 expression in neuronal cells.

Jesse Barnes, Franklin Salas, Ryan Mokhtari and 3 others

PMID 30147856

WHAT IT FOUND

Neurons grown from boys with Lowe syndrome showed disorganized F-actin and WAVE-1, unlike an engineered OCRL knockout line.

This is a cell model, not a clinical outcome.

Key findings

01Patient-derived neural cells showed disorganized F-actin staining and large patchy WAVE-1 inclusions.

02The OCRL knockout line did not show the same F-actin or WAVE-1 abnormalities.

03PI(4,5)P2 was about 25% higher in patient neural cells than in unaffected siblings and was also increased in the knockout line.

STILL TO COME

How it was doneWhat they found

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What it does not show

The study reports laboratory cell findings, not patient treatment outcomes. Only a small number of patient and control cell lines were examined. The knockout line did not replicate the patient-cell abnormalities, so the model may not match complete OCRL absence. The authors say additional knockout lines are still being generated to confirm the findings.

Declared interests

No conflict-of-interest declaration is included in the supplied text. The publication types list research support from NIH extramural, non-U.S. government, and U.S. government non-P.H.S. sources.

The easy way to misread this

Do not read the cellular changes as proof of a clinical mechanism in patients or as a reason to change therapy. The study examined cells grown from boys with Lowe syndrome, and the engineered knockout line did not show the same F-actin or WAVE-1 abnormalities.

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The study

Participants
Three boys with Lowe syndrome and their typically developing male siblings; another sibling line was generated but not analyzed
Certainty of evidence
Low

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    Cite

    Jesse Barnes, Franklin Salas, Ryan Mokhtari, et al. Modeling the neuropsychiatric manifestations of Lowe syndrome using induced pluripotent stem cells: defective F-actin polymerization and WAVE-1 expression in neuronal cells. Molecular autism. 2018.

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