ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000010.10) (NC_000010.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
22284827 "In 5 unrelated probands with microcephaly, lymphedema, and mild learning difficulties, only 1 of whom had eye abnormalities (hypermetropic astigmatism and chorioretinopathy), Ostergaard et al. (2012) performed whole-exome sequencing and identified heterozygosity for truncating mutations in the KIF11 gene (148760) in 3 of the probands. Sequencing the KIF11 gene in 9 additional unrelated probands revealed 7 more independent heterozygous KIF11 variants. Each of the 10 identified KIF11 variants was assessed in all available relatives; 2 were shown to have arisen de novo, and 8 demonstrated cosegregation with microcephaly, variable in its severity, and with a spectrum of eye and lymphatic abnormalities. Noting the substantial phenotypic overlap between MLCRD (microcephaly, primary lymphedema, and chorioretinal dysplasia) syndrome and CDMMR (chorioretinal dysplasia, microcephaly, and mental retardation) syndrome, Ostergaard et al. (2012) analyzed the KIF11 gene in 6 unrelated CDMMR families and identified heterozygous mutations in 5 of them; 1 mutation was the same nonsense mutation previously found in a family with microcephaly lymphedema. Ostergaard et al. (2012) concluded that the MLCRD and CDMMR syndromes should be considered a single entity with variable clinical features." (Summary from OMIM # 152950)
22653704 Hazan et al. 2012 report a Turkish patient with microcephaly, lymphedema, and chorioretinal dysplasia from a consanguineous family with a novel, de novo nonsense mutation in exon 2 of KIF11 (c. 139C>T, p.Arg47Ter). The variant was not present in dbSNP and it was not observed in a cohort of >600 control samples primarily of European origin.
  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity