ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000009.11) (NC_000009.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
9618165 Vollrath et al. (1998) describe variants identified in four families with nail-patella syndrome (NPS) and open-angle glaucoma, including 2 nonsense variants and 1 frameshift variant (2 bp deletion).
9837817 McIntosh et al. (1998) screened a cohort of 41 NPS families for LMX1B variants. A total of 25 variants were identified in 37 families, including 5 frameshift variants, 6 previously unreported nonsense variants, and 5 canonical splice site variants.
18414507 Bongers et al. (2008) searched for deletions of the entire LMX1B gene in families with the classical NPS phenotype by MLPA, and found deletions in three patients: 1) a de novo deletion limited to the LMX1B gene in patient 1; 2) an inherited deletion including some flanking regions in patient 2; and 3) a deletion of exons 3?8 in patient 3.

Haploinsufficiency phenotype comments:

Additional evidence includes: PMID: 31053111 Yan et al. (2019) identified a small, novel, heterozygous deletion within exon 4 of LMX1B, c.712_714delTTC, in a five-generation NPS pedigree. The variant resulted in a deletion of the conserved amino acid phenylalanine at codon 238 (p.Phe238del), which is located in the homeodomain of LMX1B. The authors postulate that this may abolish DNA binding with the molecule. PMID: 20531206 Marini et al, (2019) performed LMX1B screening on 20 Nail-Patella syndrome patients. LMX1B variants were found in 17 patients, including 1 frameshift and 2 nonsense variants. PMID: 15498463 Dunston et al. (2004) sequenced LMX1B exons and immediate flanking intron sequence in 105 unrelated individuals with NPS and identified 47 novel variants (table 1), including 13 frameshift and 6 nonsense variants.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity