TY - JOUR
T1 - Molecular (SNP) analyses of overlapping hemizygous deletions of 10q25.3 to 10qter in four patients
T2 - Evidence for HMX2 and HMX3 as candidate genes in hearing and vestibular function
AU - Miller, Nathaniel D.
AU - Nance, Melonie A.
AU - Wohler, Elizabeth S.
AU - Hoover-Fong, Julie E.
AU - Lisi, Emily
AU - Thomas, George H.
AU - Pevsner, Jonathan
PY - 2009/4
Y1 - 2009/4
N2 - 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 ∼6.1, ∼6.1, ∼12.5, and ∼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.
AB - 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 ∼6.1, ∼6.1, ∼12.5, and ∼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.
KW - 10q deletion
KW - HMX2
KW - HMX3
KW - Hearing loss
KW - SNP microarray
KW - Vestibular dysfunction
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U2 - 10.1002/ajmg.a.32705
DO - 10.1002/ajmg.a.32705
M3 - Article
C2 - 19253379
AN - SCOPUS:63749090180
SN - 1552-4825
VL - 149
SP - 669
EP - 680
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 4
ER -