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

Alasti, Fatemeh; Sadeghi, Akram; Sanati, Mohammad Hossein; Farhadi, Mohammad; Stollar, Elliot; Somers, Thomas; Camp, Guy Van

doi:10.1016/j.ajhg.2008.08.014

Cited by 26 publications

(43 citation statements)

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“…The smaller and dysmorphic pinna of TM-treated CMV::CreER T2 ;Hoxa2 lox/del mutant newborns (supplementary material Fig. S2) is reminiscent of the HOXA2 mutant phenotype in humans (Alasti et al, 2008). Analysis by in situ hybridisation confirmed the almost complete loss of Hoxa2 expression in TMtreated mutants when compared with control embryos (supplementary material Fig.…”

Section: The Eac Develops From First Arch Hoxa2mentioning

confidence: 65%

“…In humans, a HOXA2 mutation induces a bilateral microtia associated with abnormal shape of the auricle (Alasti et al, 2008). Moreover, hearing impairment and partial cleft palate have been reported (Alasti et al, 2008). A role for Hoxa2 in external ear morphogenesis is also observed in mice, where its inactivation induces duplication of the EAC and absence of the pinna (Gendron-Maguire et al, 1993;Mallo and Gridley, 1996;Mark et al, 1995;Rijli et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…Among these factors, Hoxa2 plays a crucial role. In humans, a HOXA2 mutation induces a bilateral microtia associated with abnormal shape of the auricle (Alasti et al, 2008). Moreover, hearing impairment and partial cleft palate have been reported (Alasti et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Mouse Hoxa2 mutations provide a model for microtia and auricle duplication

et al. 2013

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SUMMARYExternal ear abnormalities are frequent in newborns ranging from microtia to partial auricle duplication. Little is known about the molecular mechanisms orchestrating external ear morphogenesis. In humans, HOXA2 partial loss of function induces a bilateral microtia associated with an abnormal shape of the auricle. In mice, Hoxa2 inactivation at early gestational stages results in external auditory canal (EAC) duplication and absence of the auricle, whereas its late inactivation results in a hypomorphic auricle, mimicking the human HOXA2 mutant condition. By genetic fate mapping we found that the mouse auricle (or pinna) derives from the Hoxa2-expressing neural crest-derived mesenchyme of the second pharyngeal arch, and not from a composite of first and second arch mesenchyme as previously proposed based on morphological observation of human embryos. Moreover, the mouse EAC is entirely lined by Hoxa2-negative first arch mesenchyme and does not develop at the first pharyngeal cleft, as previously assumed. Conditional ectopic Hoxa2 expression in first arch neural crest is sufficient to induce a complete duplication of the pinna and a loss of the EAC, suggesting transformation of the first arch neural crest-derived mesenchyme lining the EAC into an ectopic pinna. Hoxa2 partly controls the morphogenesis of the pinna through the BMP signalling pathway and expression of Eya1, which in humans is involved in branchio-oto-renal syndrome. Thus, Hoxa2 loss-and gain-of-function approaches in mice provide a suitable model to investigate the molecular aetiology of microtia and auricle duplication.

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Section: The Eac Develops From First Arch Hoxa2mentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

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Mouse Hoxa2 mutations provide a model for microtia and auricle duplication

et al. 2013

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“…Moreover also been reported that the missense mutation of Hoxa-2 gene in a consanguineous Iranian family segregating for an autosomal recessive form of bilateral microtia. 16 Certainly, Hoxa-2 gene organises patterns of cell proliferation and which will contribute to the control of auricle appearance. Severerity of Hoxa-2 gene mutation corresponds to severerity of auricle morphological defect.…”

Section: Discussionmentioning

confidence: 99%

Rare defect at superior helix as morphological variation of right auricle

Parwanto

2018

Int J Res Med Sci

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Auricle is the part of external ear. Morphological appearance and biometric of auricle are influenced by genetic and environmental factors. Base on the fact that morphological appearance and biometric of auricle vary in different human ethnic races. Normal of auricle have complete component with normal of dimension and appearance. Population studies show the different of morphological and biometric of auricle. Generally, the right and left auricles in the individual is symmetrical in both size and appearance. We reported about defect at superior helix of right auricle. In this case it shows that right and left auricles have complete components. The biometric comparison of right and left auricles showed equal or not significant different. Defect of right auricle at superior helix were indentation as morphological variation.

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“…Patients with mutations in HOXA2 display severe microtia, middle ear deformities and hearing loss (Alasti et al, 2008). By contrast, OAS patients and dumbo mice have dysmorphic external ears but the middle ear and hearing appear to be unaffected (Schorderet et al, 2008;Munroe et al, 2009;Gillespie et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

A distal 594bp ECR specifies Hmx1 expression in pinna and lateral facial morphogenesis and is regulated by Hox-Pbx-Meis

Rosin

Cox

et al. 2016

Development

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Hmx1 encodes a homeodomain transcription factor expressed in the developing lateral craniofacial mesenchyme, retina and sensory ganglia. Mutation or mis-regulation of Hmx1 underlies malformations of the eye and external ear in multiple species. Deletion or insertional duplication of an evolutionarily conserved region (ECR) downstream of Hmx1 has recently been described in rat and cow, respectively. Here, we demonstrate that the impact of Hmx1 loss is greater than previously appreciated, with a variety of lateral cranioskeletal defects, auriculofacial nerve deficits, and duplication of the caudal region of the external ear. Using a transgenic approach, we demonstrate that a 594 bp sequence encompassing the ECR recapitulates specific aspects of the endogenous Hmx1 lateral facial expression pattern. Moreover, we show that Hoxa2, Meis and Pbx proteins act cooperatively on the ECR, via a core 32 bp sequence, to regulate Hmx1 expression. These studies highlight the conserved role for Hmx1 in BA2-derived tissues and provide an entry point for improved understanding of the causes of the frequent lateral facial birth defects in humans.

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

Cited by 26 publications

References 0 publications

Mouse Hoxa2 mutations provide a model for microtia and auricle duplication

Mouse Hoxa2 mutations provide a model for microtia and auricle duplication

Rare defect at superior helix as morphological variation of right auricle

A distal 594bp ECR specifies Hmx1 expression in pinna and lateral facial morphogenesis and is regulated by Hox-Pbx-Meis

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