Poelmans Simon, Kawamoto Tatsuro, Cristofoli Francesca, Politis Constantinus, Vermeesch Joris, Bailleul-Forestier Isabelle, Hens Greet, Devriendt Koenraad, Verdonck Anna, Carels Carine
Department of Oral Health Sciences-Orthodontics, KU Leuven and Dentistry, University Hospitals Leuven, Leuven, Belgium.
Department of Orthodontics and Craniofacial Biology, College of Dentistry, Radboudumc, Nijmegen, The Netherlands.
Am J Med Genet A. 2015 Oct;167A(10):2451-8. doi: 10.1002/ajmg.a.37207. Epub 2015 Jun 16.
Solitary Median Maxillary Central Incisor occurs in 1 of 50,000 live births. It is the mildest manifestation of the holoprosencephaly spectrum and is genetically heterogeneous. Here we report six patients with solitary median maxillary central incisor, and a range of other phenotypic anomalies with different degrees of severity, varying from mild signs of holoprosencephaly to associated intellectual disability, and with different genetic background. Using array comparative genomic hybridization, pathogenic copy number variants were found in three of the six patients. Two patients had a deletion at the 18p11 chromosomal region that includes TGIF1 while the other patient had a deletion at 7q36, including the SHH gene. In one patient, a mutation in SIX3 was detected with exome sequencing, while in the two remaining patients all known holoprosencephaly genes were excluded using multiplex ligation-dependent probe amplification and sequencing, and remain unsolved. One of the two latter patients had isolated solitary median maxillary central incisor without other visible dentofacial anomalies, while the other had clinical features not part of the known holoprosencephaly spectrum.
孤立性上颌中切牙在每50000例活产婴儿中出现1例。它是前脑无裂畸形谱系中最轻微的表现形式，且具有遗传异质性。在此，我们报告了6例孤立性上颌中切牙患者，以及一系列其他不同严重程度的表型异常，从轻微的前脑无裂畸形体征到相关的智力残疾不等，且具有不同的遗传背景。通过阵列比较基因组杂交，在6例患者中的3例发现了致病性拷贝数变异。2例患者在包含TGIF1的18p11染色体区域存在缺失，而另1例患者在包含SHH基因的7q36区域存在缺失。在1例患者中，通过外显子组测序检测到SIX3突变，而在其余2例患者中，使用多重连接依赖探针扩增和测序排除了所有已知的前脑无裂畸形基因，问题仍未解决。后2例患者中的1例仅有孤立性上颌中切牙，无其他明显的牙颌面异常，而另1例具有不属于已知前脑无裂畸形谱系的临床特征。
