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.2008.02.015

Cited by 91 publications

(60 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…65,66 Homeobox A2 ( HOXA2 ) mutations have been implicated in autosomal dominant and recessive forms of microtia and hearing impairment, sometimes accompanying cleft palate. 67,68 In this study, the variant identified in HOXA2 was novel.…”

Section: Discussionmentioning

confidence: 68%

Exome Sequence Analysis of 14 Families With High Myopia

Kloss

Tompson

Whisenhunt

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PurposeTo identify causal gene mutations in 14 families with autosomal dominant (AD) high myopia using exome sequencing.MethodsSelect individuals from 14 large Caucasian families with high myopia were exome sequenced. Gene variants were filtered to identify potential pathogenic changes. Sanger sequencing was used to confirm variants in original DNA, and to test for disease cosegregation in additional family members. Candidate genes and chromosomal loci previously associated with myopic refractive error and its endophenotypes were comprehensively screened.ResultsIn 14 high myopia families, we identified 73 rare and 31 novel gene variants as candidates for pathogenicity. In seven of these families, two of the novel and eight of the rare variants were within known myopia loci. A total of 104 heterozygous nonsynonymous rare variants in 104 genes were identified in 10 out of 14 probands. Each variant cosegregated with affection status. No rare variants were identified in genes known to cause myopia or in genes closest to published genome-wide association study association signals for refractive error or its endophenotypes.ConclusionsWhole exome sequencing was performed to determine gene variants implicated in the pathogenesis of AD high myopia. This study provides new genes for consideration in the pathogenesis of high myopia, and may aid in the development of genetic profiling of those at greatest risk for attendant ocular morbidities of this disorder.

show abstract

Section: Discussionmentioning

confidence: 68%

Exome Sequence Analysis of 14 Families With High Myopia

Kloss

Tompson

Whisenhunt

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…Whereas HOXA2 did not score very high compared to other members of the HOXA cluster in our prioritization analysis, it plays a critical role in development of the middle and external ear (Alasti et al 2008; O’Gorman 2005; Tischfield et al 2005; VieilleGrosjean et al 1997) and mutation of its highly conserved homeodomain has been causally implicated in autosomal recessive bilateral microtia, mixed symmetrical severe-to-profound hearing impairment and cleft palate (Alasti et al 2008). Of the other HOXA family members, a homozygous mutation of HOXA1 has been reported to disrupt the inner and outer ear and cause facial, brainstem and cardiac abnormalities (Tischfield et al 2005).…”

Section: Discussionmentioning

confidence: 75%

Genome-wide copy number variation analysis of a Branchio-oto-renal syndrome cohort identifies a recombination hotspot and implicates new candidate genes

et al. 2013

Self Cite

View full text Add to dashboard Cite

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by branchial arch anomalies, hearing loss and renal dysmorphology. Although haploinsufficiency of EYA1 and SIX1 are known to cause BOR, copy number variation analysis has only been performed on a limited number of BOR patients. In this study, we used high-resolution array-based comparative genomic hybridization (aCGH) on 32 BOR probands negative for coding-sequence and splice-site mutations in known BOR-causing genes to identify potential disease-causing genomic rearrangements. Of the >1,000 rare and novel copy number variants (CNVs) we identified, four were heterozygous deletions of EYA1 and several downstream genes that had nearly identical breakpoints associated with retroviral sequence blocks, suggesting that non-allelic homologous recombination seeded by this recombination hotspot is important in the pathogenesis of BOR. A different heterozygous deletion removing the last exon of EYA1 was identified in an additional proband. Thus in total 5 probands (14%) had deletions of all or part of EYA1. Using a novel disease-gene prioritization strategy that includes network analysis of genes associated with other deletions suggests that SHARPIN (Sipl1), FGF3 and the HOXA gene cluster may contribute to the pathogenesis of BOR.

show abstract

“…Hoxa2 is known to be important for anterior posterior patterning for both the hindbrain and second arch NCC (Gendron-Maguire et al, 1993; Rijli et al, 1993). Mutation of HOXA2 in humans can impact development of the inner ear (Alasti et al, 2008), but, again, the effect is unlikely to be mediated by the hindbrain (Bok et al, 2005). Because mutation of Hoxa2 causes significant mis-patterning of R4 NCC it is possible that abnormal anterior-posterior specification of the NCC could be responsible for human HOXA2 inner ear defects.…”

Section: Discussionmentioning

confidence: 99%

Cochleovestibular nerve development is integrated with migratory neural crest cells

Sandell

Tjaden

Barlow

et al. 2014

Developmental Biology

View full text Add to dashboard Cite

The cochleovestibular (CV) nerve, which connects the inner ear to the brain, is the nerve that enables the senses of hearing and balance. The aim of this study was to document the morphological development of the mouse CV nerve with respect to the two embryonic cells types that produce it, specifically, the otic vesicle-derived progenitors that give rise to neurons, and the neural crest cell (NCC) progenitors that give rise to glia. Otic tissues of mouse embryos carrying NCC lineage reporter transgenes were whole mount immunostained to identify neurons and NCC. Serial optical sections were collected by confocal microscopy and were compiled to render the three dimensional (3D) structure of the developing CV nerve. Spatial organization of the NCC and developing neurons suggest that neuronal and glial populations of the CV nerve develop in tandem from early stages of nerve formation. NCC form a sheath surrounding the CV ganglia and central axons. NCC are also closely associated with neurites projecting peripherally during formation of the vestibular and cochlear nerves. Physical ablation of NCC in chick embryos demonstrates that survival or regeneration of even a few individual NCC from ectopic positions in the hindbrain results in central projection of axons precisely following ectopic pathways made by regenerating NCC.

show abstract

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

Cited by 91 publications

References 59 publications

Exome Sequence Analysis of 14 Families With High Myopia

Exome Sequence Analysis of 14 Families With High Myopia

Genome-wide copy number variation analysis of a Branchio-oto-renal syndrome cohort identifies a recombination hotspot and implicates new candidate genes

Cochleovestibular nerve development is integrated with migratory neural crest cells

Contact Info

Product

Resources

About