Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations

BMC Medical Genetics

Alan J Mighell¹  Chris F Inglehearn³  Colin A Johnson³  Claire E L Smith³  Clare V Logan³  David A Parry²  Lilian M Paula⁴  Paulo Marcio Yamaguti⁴  Luiz Claudio Castro⁵  Caroline Lourenço de Lima⁴  Priscila Gomes Alves⁴  James A Poulter³  Ana Carolina Acevedo⁴ 

[1] Department of Oral Medicine, School of Dentistry, University of Leeds, Leeds, UK;Section of Genetics, School of Medicine, University of Leeds, Leeds, UK;Section of Ophthalmology and Neuroscience, University of Leeds, Leeds, UK;Oral Care Center for Inherited Diseases, University Hospital of Brasilia, Department of Dentistry, Health Sciences School, University of Brasilia, Brasilia, Brazil;Department of Pediatrics, School of Medicine, University of Brasilia, Brasilia, Brazil

关键词: Ectopic mineralisation;    Bone mineralization;    Dentine;    Amelogenesis imperfecta;    FAM20C;    Raine syndrome;   

Others  :  1171813
DOI  :  10.1186/s12881-015-0154-5

 received in 2014-11-26, accepted in 2015-02-06,  发布年份 2015

【 摘 要 】

Background

Raine syndrome (RS) is a rare autosomal recessive bone dysplasia typified by osteosclerosis and dysmorphic facies due to FAM20C mutations. Initially reported as lethal in infancy, survival is possible into adulthood. We describe the molecular analysis and clinical phenotypes of five individuals from two consanguineous Brazilian families with attenuated Raine Syndrome with previously unreported features.

Methods

The medical and dental clinical records were reviewed. Extracted deciduous and permanent teeth as well as oral soft tissues were analysed. Whole exome sequencing was undertaken and FAM20C cDNA sequenced in family 1.

Results

Family 1 included 3 siblings with hypoplastic Amelogenesis Imperfecta (AI) (inherited abnormal dental enamel formation). Mild facial dysmorphism was noted in the absence of other obvious skeletal or growth abnormalities. A mild hypophosphataemia and soft tissue ectopic mineralization were present. A homozygous FAM20C donor splice site mutation (c.784 + 5 g > c) was identified which led to abnormal cDNA sequence. Family 2 included 2 siblings with hypoplastic AI and tooth dentine abnormalities as part of a more obvious syndrome with facial dysmorphism. There was hypophosphataemia, soft tissue ectopic mineralization, but no osteosclerosis. A homozygous missense mutation in FAM20C (c.1487C > T; p.P496L) was identified.

Conclusions

The clinical phenotype of non-lethal Raine Syndrome is more variable, including between affected siblings, than previously described and an adverse impact on bone growth and health may not be a prominent feature. By contrast, a profound failure of dental enamel formation leading to a distinctive hypoplastic AI in all teeth should alert clinicians to the possibility of FAM20C mutations.

【 授权许可】

   
2015 Acevedo et al.; licensee BioMed Central.

【 图 表 】

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