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APP – Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch type

Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch type (HCHWA-D) is an autosomal dominant cerebral amyloid angiopathy caused by a point mutation in exon 17 of the APP gene. A hiPSC line generated from a symptomatic HCHWA-D patient carries the Dutch mutation, retains normal karyotype and pluripotency marker expression, and can differentiate into all three germ layers in vitro (PMID:30611017). No additional segregation or family studies have been reported to date, and direct assays of vascular amyloid deposition in this model are pending.

Key Take-home: Screening for the APP Dutch variant enables definitive diagnosis and familial counseling in suspected cases of cerebral amyloid angiopathy.

References

  • Stem cell research • 2019 • Generation of 3 human induced pluripotent stem cell lines LUMCi005-A, B and C from a Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch type patient. PMID:30611017

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Single proband with Dutch APP mutation and hiPSC derivation; no segregation data ([PMID:30611017])

Genetic Evidence

Limited

One proband harboring the exon 17 Dutch variant; no additional families or segregation studies provided ([PMID:30611017])

Functional Evidence

Limited

hiPSC model confirms mutation carriage, pluripotency and differentiation but lacks direct vascular amyloid assays ([PMID:30611017])