Inherited intragenic PBX1 deletion: Expanding the phenotype

Am J Med Genet A. 2021 Jan;185(1):234-237. doi: 10.1002/ajmg.a.61932. Epub 2020 Oct 24.

Abstract

PBX1 encodes the pre-B cell leukemia homeobox transcription factor, a three amino acid loop extension (TALE) homeodomain transcription factor, which forms nuclear complexes with other TALE class homeodomain proteins that ultimately regulate target genes controlling organ patterning during embryogenesis. Heterozygous de novo pathogenic variants in PBX1 resulting in haploinsufficiency are associated with congenital anomalies of the kidneys and urinary tract, most commonly renal hypoplasia, as well as anomalies involving the external ear, branchial arch, heart, and genitalia, and they cause intellectual disability and developmental delay. Affected individuals described thus far have had de novo variants. Here, we report three related individuals with an inherited pathogenic intragenic PBX1 deletion with variable clinical features typical for this syndrome.

Keywords: PBX1; congenital anomalies; intragenic deletion; variable expression.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Child
  • Coloboma / diagnosis
  • Coloboma / genetics*
  • Coloboma / pathology
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics
  • Developmental Disabilities / pathology
  • Female
  • Genetic Predisposition to Disease*
  • Haploinsufficiency / genetics
  • Humans
  • Infant
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics
  • Intellectual Disability / pathology
  • Male
  • Mutation / genetics
  • Phenotype
  • Pre-B-Cell Leukemia Transcription Factor 1 / genetics*
  • Renal Insufficiency / diagnosis
  • Renal Insufficiency / genetics*
  • Renal Insufficiency / pathology
  • Urogenital Abnormalities / genetics*
  • Urogenital Abnormalities / pathology
  • Vesico-Ureteral Reflux / diagnosis
  • Vesico-Ureteral Reflux / genetics*
  • Vesico-Ureteral Reflux / pathology

Substances

  • Pre-B-Cell Leukemia Transcription Factor 1
  • pbx1 protein, human

Supplementary concepts

  • Cakut
  • Papillorenal syndrome