Molecular (SNP) analyses of overlapping hemizygous deletions of 10q25.3 to 10qter in four patients: evidence for HMX2 and HMX3 as candidate genes in hearing and vestibular function

Am J Med Genet A. 2009 Feb 15;149A(4):669-80. doi: 10.1002/ajmg.a.32705.


We report on the analyses of four unrelated patients with de novo, overlapping, hemizygous deletions of the long arm of chromosome 10. These include two small terminal deletions (10q26.2 to 10qter), a larger terminal deletion (10q26.12 to 10qter), and an interstitial deletion (10q25.3q26.13). Single nucleotide polymorphism (SNP) studies (Illumina 550 K) established that these deletions resulted in the hemizygous loss of approximately 6.1, approximately 6.1, approximately 12.5, and approximately 7.0 Mb respectively. Additionally, these data establish that Patients 1, 2, and 3 share common, distal, hemizygous deleted regions of 6.09 Mb containing 37 RefSeq genes. Patients 3 and 4 share a 2.52 Mb deleted region corresponding to the proximal deleted region of Patient 3 and the distal deleted region of Patient 4. This common, hemizygous region contains 20 RefSeq genes including two H6 family homeobox genes (HMX2 and HMX3). Based on previous reports that Hmx2/Hmx3 knockout mice have vestibular anomalies, we propose that hemizygous deletions of HMX2 and HMX3 are responsible for the inner ear malformations observed from CT images, vestibular dysfunction, and congenital sensorineural hearing loss found in Patients 3 and 4.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 10 / genetics*
  • Ear, Inner / abnormalities*
  • Ear, Inner / diagnostic imaging
  • Female
  • Genes, Homeobox*
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / pathology
  • Hearing Loss, Sensorineural / physiopathology
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Karyotyping
  • Male
  • Polymorphism, Single Nucleotide
  • Tomography, X-Ray Computed
  • Vestibule, Labyrinth / physiopathology*