ClinGen Dosage Sensitivity Curation Page

PAFAH1B1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000017.10) (NC_000017.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
11754098 Cardoso et al. (2002) provide a mutation update on PAFAH1B1 (LIS1), including de novo intragenic mutations from 41 patients with lissencephaly (4 from the current report and others from previous publications). Six de novo nonsense mutations are included in this publication.
20452996 Bruno et al. (2010) further characterize genotype and phenotype correlations within the 17p13.3 microdeletion and microduplication region.
See GeneReviews for additional mutations.

Triplosensitivity phenotype comment:

PAFAH1B1 is located within the 17p13.3 duplication syndrome with developmental delay and other features (PMID:19520700 Roos et al. 2009). PMID:19136950 Bi et al. (2009) reported on 7 patients with duplications in 17p13. Four patients have duplications including YWHAE, two patients have gains including PAFAH1B1, and one patient has a gain that includes both genes. Subjects 5 and 6 have gains of PAFAH1B1 (and not YWHAE), but there are also 6 additional genes in these imbalances. Based on phenotype comparisons of patients with YWHAE duplications versus PAFAH1B1 duplications, the authors suggest that gain of PAFAH1B1 causes subtle brain abnormalities, developmental delay, and relative microcephaly.