Mutational analysis of GSC, HOXA2 and PRKRA in 106 Chinese patients with microtia

Hao, Shaojuan; Jin, Lei; Li, Chenlong; Wang, Huijun; Zheng, Fengyun; Ma, Ding; Zhang, Tianyu

doi:10.1016/j.ijporl.2016.12.026

Cited by 9 publications

(12 citation statements)

References 32 publications

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“…13,14,27,28 According to the MARX classification, 10 the HOXA2 gene was common in the form of microtia type II and was exclusive to isolated microtia. 1,17,22,41,[47][48][49][50] However, no specific type of microtia has been linked to the deletion of TCOF1. 10,51 The field of genetic variables in microtia research is still relatively extensive.…”

Section: Discussionmentioning

confidence: 99%

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The role of genetic factors in microtia: A systematic review

Putri

Stephanie²,

Pramanasari³

et al. 2022

F1000Res

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Background: Microtia is a congenital malformation of the outer ears caused by improper embryonic development. The origin of microtia and causes of its variations remain unknown. Because of the lack of clarity regarding the role of genetic variables in microtia, we conducted a systematic review to qualitatively identify the genes most important in the development of microtia to provide an up-to-date review. Methods: Using six search engines, we searched all published studies related to the genetic factors of isolated microtia and syndromic microtia. The identified publications were screened and selected based on inclusion and exclusion criteria by the authors and assessed for methodological quality using the Joanna Briggs Institute (JBI) critical appraisal tools. We found 40 studies, including 22 studies on syndromic microtia and 18 studies on isolated microtia. Data extraction of each study was arranged in tabulation for syndromic and isolated microtia. The extracted data were: first author’s surname, year of publication, country of origin, study design, sample characteristic and gene assessed. Results: After the data were extracted, analyzed, and reviewed, the most common gene suspected to be involved in isolated microtia was Homeobox A2 (HOXA2, 12.1%). Conversely, in syndromic microtia, the two most common genes supposed to play a role were Fibroblast Growth Factor 3 (FGF3, 47.2%) and Treacher–Collins–Franceschetti syndrome 1 (TCOF1, 30.2%). From the studies, the three most prevalent genes associated with microtia were HOXA2 (10%), FGF3 (8.4%), and TCOF1 (5.4%). In syndromic microtia, the most common mutation types were deletion in TCOF1 (46.9%) and missense and deletion in FGF3 (both 38%), and in isolated microtia, the most common mutation type was silent in HOXA2 (54.2%). Conclusions: In summary, genetic factors are involved in microtia; thus, molecular analysis is strongly advised. PROSPERO registration: CRD42021287294 (25/10/21).

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Section: Discussionmentioning

confidence: 99%

“…Characteristic of the studies of syndromic microtia 13,14,[33][34][35][37][38]48,[53][54][55][56][57][58][59][61][62][63][64]73, …”

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confidence: 99%

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The role of genetic factors in microtia: A systematic review

Putri

Stephanie²,

Pramanasari³

et al. 2022

F1000Res

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“…Identification of pathogenic mutations in HOXA2 was reported in three different isolated bilateral microtia families [ 23 – 25 ], prompting researchers to propose that HOXA2 may be among genes responsible for the pathogenesis of isolated microtia. However, studies that have focused on sporadic microtia patients have found no pathogenic mutations in HOXA2 [ 26 , 27 ]. Consistent with this, we failed to identify any mutations in HOXA2 , suggesting that there may be distinct etiologies that result in isolated microtia.…”

Section: Discussionmentioning

confidence: 99%

Target sequencing of 307 deafness genes identifies candidate genes implicated in microtia

et al. 2017

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Microtia is a congenital malformation of the external ear caused by genetic and/or environmental factors. However, no causal genetic mutations have been identified in isolated microtia patients. In this study, we utilized targeted genomic capturing combined with next-generation sequencing to screen for mutations in 307 deafness genes in 32 microtia patients. Forty-two rare heterozygous mutations in 25 genes, including 22 novel mutations in 24 isolated unilateral microtia cases were identified. Pathway analysis found five pathways especially focal adhesion pathway and ECM-receptor interaction pathway were significantly associated with microtia. The low-frequency variants association study was used and highlighted several strong candidate genes MUC4, MUC6, COL4A4, MYO7A, AKAP12, COL11A1, DSPP, ESPN, GPR98, PCDH15, BSN, CACNA1D, TPRN, and USH1C for microtia (P = 2.51 × 10−4). Among these genes, COL4A4 and COL11A1 may lead to microtia through focal adhesion pathway and ECM-receptor interaction pathway which are connected to the downstream Wnt signaling pathway. The present results indicate that certain genes may affect both external/middle and inner ear development, and demonstrate the benefits of using a capture array in microtia patients.

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“…However, genes responsible for nonsyndromic microtia have not been identified and validated in human. Recent attempts to identify such genes include the sequencing of PRKRA , PACT , GSC , HOXA2 and SIX2 in microtia-atresia patients, which may be pathogenic genes underlying microtia-atresia, but no mutations have been identified [17–20].…”

Section: Introductionmentioning

confidence: 99%

Identification of sequence variants associated with severe microtia-astresia by targeted sequencing

Wang

Fan

et al. 2019

BMC Med Genomics

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BackgroundMicrotia-atresia is characterized by abnormalities of the auricle (microtia) and aplasia or hypoplasia of the external auditory canal, often associated with middle ear abnormalities. To date, no causal genetic mutations or genes have been identified in microtia-atresia patients.MethodsWe designed a panel of 131 genes associated with external/middle or inner ear deformity. Targeted genomic capturing combined with next-generation sequencing (NGS) was utilized to screen for mutations in 40 severe microtia-atresia patients. Mutations detected by NGS were filtered and validated. And then mutations were divided into three categories—rare or novel variants, low-frequency variants and common variants—based on their frequency in the public database. The rare or novel mutations were prioritized by pathogenicity analysis. For the low-frequency variants and common variants, we used association studies to explore risk factors of severe microtia-atresia.ResultsSixty-five rare heterozygous mutations of 42 genes were identified in 27 (67.5%) severe microtia-atresia patients. Association studies to determine genes that were potentially pathogenic found that PLEC, USH2A, FREM2, DCHS1, GLI3, POMT1 and GBA genes were significantly associated with severe microtia-atresia. Of these, DCHS1 was strongly suggested to cause severe microtia-atresia as it was identified by both low-frequency and common variants association studies. A rare mutation (c.481C > T, p.R161C) in DCHS1 identified in one individual may be deleterious and may cause severe microtia-atresia.ConclusionWe identified several genes that were significantly associated with severe microtia-atresia. The findings provide new insights into genetic background of external ear deformities.Electronic supplementary materialThe online version of this article (10.1186/s12920-019-0475-x) contains supplementary material, which is available to authorized users.

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Mutational analysis of GSC, HOXA2 and PRKRA in 106 Chinese patients with microtia

Cited by 9 publications

References 32 publications

The role of genetic factors in microtia: A systematic review

The role of genetic factors in microtia: A systematic review

Target sequencing of 307 deafness genes identifies candidate genes implicated in microtia

Identification of sequence variants associated with severe microtia-astresia by targeted sequencing

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