Acevedo Ana Carolina, Poulter James A, Alves Priscila Gomes, de Lima Caroline Lourenço, Castro Luiz Claudio, Yamaguti Paulo Marcio, Paula Lilian M, Parry David A, Logan Clare V, Smith Claire E L, Johnson Colin A, Inglehearn Chris F, Mighell Alan J
Oral Care Center for Inherited Diseases, University Hospital of Brasilia, Department of Dentistry, Health Sciences School, University of Brasilia, Brasilia, Brazil.
Section of Ophthalmology and Neuroscience, University of Leeds, Leeds, UK.
BMC Med Genet. 2015 Feb 21;16:8. doi: 10.1186/s12881-015-0154-5.
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.
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.
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.
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.
雷恩综合征（RS）是一种罕见的常染色体隐性骨发育不良，因FAM20C基因突变导致骨硬化和面部畸形。最初报道该疾病在婴儿期致死，但也有可能存活至成年期。我们描述了来自两个巴西近亲家庭的五名个体的分子分析和临床表型，这些个体患有症状较轻的雷恩综合征，具有先前未报道的特征。
回顾了医学和牙科临床记录。对拔除的乳牙和恒牙以及口腔软组织进行了分析。进行了全外显子组测序，并对家族1中的FAM20C cDNA进行了测序。
家族1包括3名患有牙釉质发育不全（AI）（遗传性牙釉质形成异常）的兄弟姐妹。在没有其他明显骨骼或生长异常的情况下，发现有轻度面部畸形。存在轻度低磷血症和软组织异位矿化。鉴定出一个纯合的FAM20C供体剪接位点突变（c.784 + 5 g > c），该突变导致cDNA序列异常。家族2包括2名患有牙釉质发育不全和牙齿牙本质异常的兄弟姐妹，这是更明显的面部畸形综合征的一部分。存在低磷血症、软组织异位矿化，但无骨硬化。鉴定出FAM20C中的一个纯合错义突变（c.1487C > T；p.P496L）。
非致死性雷恩综合征的临床表型比先前描述的更具变异性，包括在受影响的兄弟姐妹之间，对骨骼生长和健康的不利影响可能不是一个突出特征。相比之下，牙釉质形成的严重失败导致所有牙齿出现独特的发育不全性AI，应提醒临床医生注意FAM20C突变的可能性。
