Review: children &lt;2 years of age with bilateral acute otitis media and children with otorrhoea benefit most from antibiotics

Williamson, Ian

doi:10.1136/ebm.12.2.47

Cited by 1 publication

(1 citation statement)

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“…Although most of the microtic patients have a normal inner ear, 17,52 the combination of microtia with inner-ear anomalies has also been reported. 17 A Japanese family was reported with inner-ear semicircular canal malformation and external-and middle-ear abnormalities.…”

Section: Discussionmentioning

confidence: 99%

A Mutation in HOXA2 Is Responsible for Autosomal-Recessive Microtia in an Iranian Family

Alasti

Sadeghi

Sanati

et al. 2008

The American Journal of Human Genetics

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Microtia, a congenital deformity manifesting as an abnormally shaped or absent external ear, occurs in one out of 8,000-10,000 births. We ascertained a consanguineous Iranian family segregating with autosomal-recessive bilateral microtia, mixed symmetrical severe to profound hearing impairment, and partial cleft palate. Genome-wide linkage analysis localized the responsible gene to chromosome 7p14.3-p15.3 with a maximum multi-point LOD score of 4.17. In this region, homeobox genes from the HOXA cluster were the most interesting candidates. Subsequent DNA sequence analysis of the HOXA1 and HOXA2 homeobox genes from the candidate region identified an interesting HOXA2 homeodomain variant: a change in a highly conserved amino acid (p.Q186K). The variant was not found in 231 Iranian and 109 Belgian control samples. The critical contribution of HoxA2 for auditory-system development has already been shown in mouse models. We built a homology model to predict the effect of this mutation on the structure and DNA-binding activity of the homeodomain by using the program Modeler 8v2. In the model of the mutant homeodomain, the position of the mutant lysine side chain is consistently farther away from a nearby phosphate group; this altered position results in the loss of a hydrogen bond and affects the DNA-binding activity.

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Section: Discussionmentioning

confidence: 99%