Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations.
Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations.
复制标题
DOI：
10.1186/s12881-015-0154-5
复制
发表时间：
2015-02-21
影响因子：
--
通讯作者：
Mighell AJ
中科院分区：
文献类型：
--
作者：
Acevedo AC;Poulter JA;Alves PG;de Lima CL;Castro LC;Yamaguti PM;Paula LM;Parry DA;Logan CV;Smith CE;Johnson CA;Inglehearn CF;Mighell AJ
雷恩综合征（RS）是一种罕见的常染色体隐性遗传性骨发育不良，以FAM 20 C突变引起的骨质疏松和畸形面容为典型特征。最初报道在婴儿期是致命的，但成年后仍有可能存活。我们描述的分子分析和临床表型的五个人从两个血缘巴西家庭与减毒雷恩综合征与以前未报道的功能。审查了医疗和牙科临床记录。分析了拔除的乳牙和恒牙以及口腔软组织。进行全外显子组测序，并对家族1中的FAM 20 C cDNA进行测序。家族1包括3名患有发育不良性釉质发育不全（AI）（遗传性异常牙釉质形成）的兄弟姐妹。在没有其他明显骨骼或生长异常的情况下，观察到轻度面部畸形。存在轻度低磷血症和软组织异位矿化。鉴定出纯合FAM 20 C供体剪接位点突变（c.784 + 5 g > c），导致cDNA序列异常。家族2包括2名发育不全AI和牙本质异常的兄弟姐妹，作为更明显的面部畸形综合征的一部分。有低磷血症，软组织异位矿化，但没有骨质疏松。在FAM 20 C中鉴定到纯合错义突变（c.1487C > T; p.P496L）。非致死性Raine综合征的临床表型比以前描述的更易变，包括受影响的兄弟姐妹之间，并且对骨生长和健康的不利影响可能不是突出特征。相比之下，牙釉质形成的严重失败导致所有牙齿中独特的发育不全AI应该提醒临床医生FAM 20 C突变的可能性。本文的在线版本（doi：10.1186/s12881-015-0154-5）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1186/s12881-015-0154-5) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
14.9
作者：
Hebsgaard, SM;Korning, PG;Brunak, S
通讯作者：
Brunak, S
影响因子：
2.9
作者：
Fisher, LW;Fedarko, NS
通讯作者：
Fedarko, NS
影响因子：
2
作者：
Ababneh, Farouq K.;AlSwaid, Abdulrahman;AlBalwi, Mohammed A.
通讯作者：
AlBalwi, Mohammed A.
影响因子：
3.7
作者：
Ishikawa HO;Xu A;Ogura E;Manning G;Irvine KD
通讯作者：
Irvine KD
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--