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Phenotype variation in Treacher Collins Syndrome: from missense to splice site mutations
Available online at www.sciencedirect.com
British Journal of Oral and Maxillofacial Surgery 51 (2013) 276–277
Letters to the Editor
Re: Craniofacial development: current concepts in the molecular basis of Treacher Collins syndrome Sir, We commend van Gijn et al.1 for their publication on the molecular basis of Treacher-Collins syndrome and we agree with them about the salient points. However, we would like to bring to the reader’s attention points that were not raised and in our opinion are pertinent. First, we agree that mutations in Treacle are responsible for a reduction in ribosomal stability, but it is clear that not all patients have these mutations. It has been shown in a study by Dauwerse et al. that other mutations can produce the same phenotype as those in Treacle.2 They are called POLR1C and POLR1D and they are 2 genes that encode for ribosomal RNA polymerases I and III. In the study they identified 20 heterozygous mutations in 252 patients identified clinically with Treacher Collins syndrome, which showed that patients with no Treacle mutations still need genetic assessment. Secondly, the authors mentioned genotype–phenotype correlation. We agree that there is a difficulty in this area because of the variation in phenotypes despite high penetrance. Teber et al. analysed the range of phenotypic expression in 46 patients and showed that although there is no genotype–phenotype correlation, awareness is needed that some specific mutations such as splice site mutations may lead to a more severe phenotype. Milder phenotypes are more commonly seen when missense mutations are present.3
2. Dauwerse JG, Dixon J, Seland S, et al. Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nat Genet 2011;43:20–2. 3. Teber OA, Gillessen-Kaesbach G, Fischer S, et al. Genotyping in 46 patients with tentative diagnosis of Treacher Collins syndrome revealed unexpected phenotypic variation. Eur J Hum Genet 2004;12:879–90.
Ben Green ∗ King’s College London School of Medicine, London, UK Dariush Nikkhah Department of Plastic surgery, Queen Victoria Hospital, East Grinstead, UK Alistair R.M. Cobb South West Cleft Service & Department of Oral and Maxillofacial Surgery, North Bristol NHS Trust, UK David J. Dunaway Craniofacial Centre, Great Ormond Street Hospital for Children, London, UK ∗ Corresponding author at: King’s College London, Academic centre, 1st floor, Henriette Raphael House, London Bridge, London, SE1 1UL. E-mail addresses: [email protected] (B. Green), [email protected] (D. Nikkhah), [email protected] (A.R.M. Cobb), [email protected] (D.J. Dunaway) Available online 27 December 2012 http://dx.doi.org/10.1016/j.bjoms.2012.12.001
Phenotype variation in Treacher Collins Syndrome: from missense to splice site mutations
Conflict of interest None.
References 1. van Gijn DR, Tucker AS, Cobourne MT. Craniofacial development: current concepts in the molecular basis of Treacher Collins syndrome. Br J Oral Maxillofac Surg 2012 [Epub ahead of print].
We thank the authors of this letter for their interest in our article.1 The paper was intended to be a general overview for the maxillofacial surgeon rather than a definitive narrative on the molecular basis of Treacher Collins syndrome, but we agree that it is important to recognise that other mutations can also be responsible for the condition. We also acknowledge the fact that splice site mutations may lead to a more severe phenotype, whilst missense mutations may be associated with milder phenotypes.
0266-4356/$ – see front matter © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Letters to the Editor / British Journal of Oral and Maxillofacial Surgery 51 (2013) 276–277
These are all important points and we appreciate the authors taking the time to make them.
Conflict of interest There are no conflicts of interest.
Reference 1. van Gijn DR, Tucker AS, Cobourne MT. Craniofacial development: current concepts in the molecular basis of Treacher Collins syndrome. Br J Oral Maxillofac Surg 2012 [Epub ahead of print].
Daniel Richard van Gijn ∗ King’s College London, United Kingdom Abigail S. Tucker Department of Craniofacial Development and Orthodontics, King’s College London, Dental Institute, United Kingdom Martyn T. Cobourne 1 King’s College London, Dental Institute, Department of Craniofacial Development and Orthodontics, Floor 27, Tower Wing, Guy’s Hospital, London SE1 9RT, United Kingdom ∗ Corresponding author. Tel.: +44 7771610960. E-mail addresses: [email protected] (D.R. van Gijn), [email protected] (A.S. Tucker), [email protected] (M.T. Cobourne) 1 Tel.: +44 2071888028. Available online 23 January 2013 http://dx.doi.org/10.1016/j.bjoms.2012.12.002
Extraction or coronectomy for third molars Sir,
277
The National Institute for Health and Clinical Excellence (NICE) has produced guidelines on the appropriate time to remove impacted third molars, but Gleeson et al. and others cited make no mention of this. The number of coronectomies reported leads me to question why coronectomy was selected rather than extraction. Is coronectomy rather than extraction to be used for all impacted third molars except for the exclusions mentioned in the paper? If so, will it be considered a failure of the duty of care if an impacted third molar that satisfied NICE criteria for extraction later becomes symptomatic after coronectomy? If the inferior dental nerve is damaged or if it is not noticed that a root has inadvertently loosened or the remnants have become symptomatic, would the technique be considered inadequate? Does coronectomy have a risk of other complications in the short and long term? The thrust of this paper and of others cited is likely to encourage coronectomy to be done by all general dental practitioners as it may be considered easier than extraction, but I know of no objective scientific evidence that compares outcomes with different levels of surgical skill and experience. How can patients give fully informed consent when objective information is based on such scant scientific evidence? This paper and others raise more questions than they answer.
Reference 1. Gleeson CF, Patel V, Kwok J, Sproat C. Coronectomy practice. Paper 1. Technique and trouble-shooting. Br J Oral Maxillofac Surg 2012;50:739–44.
Geoffrey David Wood (BDS, MSc, MDS, FDSRCPS) ∗ Spire Murrayfield Hospital, Holmwood Drive, Thingwall, Merseyside CH61 1AU, United Kingdom ∗ Tel.: +44 0151 929 5198; fax: +44 0151 648 7684. E-mail address: [email protected] Available online 4 February 2013
Re: Gleeson CF, Patel V, Kwok J, Sproat C. Coronectomy practice. Paper 1. Technique and trouble-shooting.1
http://dx.doi.org/10.1016/j.bjoms.2013.01.006
British Journal of Oral and Maxillofacial Surgery 51 (2013) 276–277
Letters to the Editor
Re: Craniofacial development: current concepts in the molecular basis of Treacher Collins syndrome Sir, We commend van Gijn et al.1 for their publication on the molecular basis of Treacher-Collins syndrome and we agree with them about the salient points. However, we would like to bring to the reader’s attention points that were not raised and in our opinion are pertinent. First, we agree that mutations in Treacle are responsible for a reduction in ribosomal stability, but it is clear that not all patients have these mutations. It has been shown in a study by Dauwerse et al. that other mutations can produce the same phenotype as those in Treacle.2 They are called POLR1C and POLR1D and they are 2 genes that encode for ribosomal RNA polymerases I and III. In the study they identified 20 heterozygous mutations in 252 patients identified clinically with Treacher Collins syndrome, which showed that patients with no Treacle mutations still need genetic assessment. Secondly, the authors mentioned genotype–phenotype correlation. We agree that there is a difficulty in this area because of the variation in phenotypes despite high penetrance. Teber et al. analysed the range of phenotypic expression in 46 patients and showed that although there is no genotype–phenotype correlation, awareness is needed that some specific mutations such as splice site mutations may lead to a more severe phenotype. Milder phenotypes are more commonly seen when missense mutations are present.3
2. Dauwerse JG, Dixon J, Seland S, et al. Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nat Genet 2011;43:20–2. 3. Teber OA, Gillessen-Kaesbach G, Fischer S, et al. Genotyping in 46 patients with tentative diagnosis of Treacher Collins syndrome revealed unexpected phenotypic variation. Eur J Hum Genet 2004;12:879–90.
Ben Green ∗ King’s College London School of Medicine, London, UK Dariush Nikkhah Department of Plastic surgery, Queen Victoria Hospital, East Grinstead, UK Alistair R.M. Cobb South West Cleft Service & Department of Oral and Maxillofacial Surgery, North Bristol NHS Trust, UK David J. Dunaway Craniofacial Centre, Great Ormond Street Hospital for Children, London, UK ∗ Corresponding author at: King’s College London, Academic centre, 1st floor, Henriette Raphael House, London Bridge, London, SE1 1UL. E-mail addresses: [email protected] (B. Green), [email protected] (D. Nikkhah), [email protected] (A.R.M. Cobb), [email protected] (D.J. Dunaway) Available online 27 December 2012 http://dx.doi.org/10.1016/j.bjoms.2012.12.001
Phenotype variation in Treacher Collins Syndrome: from missense to splice site mutations
Conflict of interest None.
References 1. van Gijn DR, Tucker AS, Cobourne MT. Craniofacial development: current concepts in the molecular basis of Treacher Collins syndrome. Br J Oral Maxillofac Surg 2012 [Epub ahead of print].
We thank the authors of this letter for their interest in our article.1 The paper was intended to be a general overview for the maxillofacial surgeon rather than a definitive narrative on the molecular basis of Treacher Collins syndrome, but we agree that it is important to recognise that other mutations can also be responsible for the condition. We also acknowledge the fact that splice site mutations may lead to a more severe phenotype, whilst missense mutations may be associated with milder phenotypes.
0266-4356/$ – see front matter © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Letters to the Editor / British Journal of Oral and Maxillofacial Surgery 51 (2013) 276–277
These are all important points and we appreciate the authors taking the time to make them.
Conflict of interest There are no conflicts of interest.
Reference 1. van Gijn DR, Tucker AS, Cobourne MT. Craniofacial development: current concepts in the molecular basis of Treacher Collins syndrome. Br J Oral Maxillofac Surg 2012 [Epub ahead of print].
Daniel Richard van Gijn ∗ King’s College London, United Kingdom Abigail S. Tucker Department of Craniofacial Development and Orthodontics, King’s College London, Dental Institute, United Kingdom Martyn T. Cobourne 1 King’s College London, Dental Institute, Department of Craniofacial Development and Orthodontics, Floor 27, Tower Wing, Guy’s Hospital, London SE1 9RT, United Kingdom ∗ Corresponding author. Tel.: +44 7771610960. E-mail addresses: [email protected] (D.R. van Gijn), [email protected] (A.S. Tucker), [email protected] (M.T. Cobourne) 1 Tel.: +44 2071888028. Available online 23 January 2013 http://dx.doi.org/10.1016/j.bjoms.2012.12.002
Extraction or coronectomy for third molars Sir,
277
The National Institute for Health and Clinical Excellence (NICE) has produced guidelines on the appropriate time to remove impacted third molars, but Gleeson et al. and others cited make no mention of this. The number of coronectomies reported leads me to question why coronectomy was selected rather than extraction. Is coronectomy rather than extraction to be used for all impacted third molars except for the exclusions mentioned in the paper? If so, will it be considered a failure of the duty of care if an impacted third molar that satisfied NICE criteria for extraction later becomes symptomatic after coronectomy? If the inferior dental nerve is damaged or if it is not noticed that a root has inadvertently loosened or the remnants have become symptomatic, would the technique be considered inadequate? Does coronectomy have a risk of other complications in the short and long term? The thrust of this paper and of others cited is likely to encourage coronectomy to be done by all general dental practitioners as it may be considered easier than extraction, but I know of no objective scientific evidence that compares outcomes with different levels of surgical skill and experience. How can patients give fully informed consent when objective information is based on such scant scientific evidence? This paper and others raise more questions than they answer.
Reference 1. Gleeson CF, Patel V, Kwok J, Sproat C. Coronectomy practice. Paper 1. Technique and trouble-shooting. Br J Oral Maxillofac Surg 2012;50:739–44.
Geoffrey David Wood (BDS, MSc, MDS, FDSRCPS) ∗ Spire Murrayfield Hospital, Holmwood Drive, Thingwall, Merseyside CH61 1AU, United Kingdom ∗ Tel.: +44 0151 929 5198; fax: +44 0151 648 7684. E-mail address: [email protected] Available online 4 February 2013
Re: Gleeson CF, Patel V, Kwok J, Sproat C. Coronectomy practice. Paper 1. Technique and trouble-shooting.1
http://dx.doi.org/10.1016/j.bjoms.2013.01.006