A new frontonasal dysplasia syndrome associated with deletion of the SIX2 gene

作者：Hufnagel Robert B; Zimmerman Sarah L; Krueger Laura A; Bender Patricia L; Ahmed Zubair M; Saal Howard M^*

来源：American Journal of Medical Genetics, Part A, 2016, 170(2): 487-491.

DOI：10.1002/ajmg.a.37441

• frontonasal dysplasia
• Brachyrrhine
• craniosynostosis
• ptosis
• hypertelorism

The frontonasal dysplasias are a group of craniofacial phenotypes characterized by hypertelorism, nasal clefting, frontal bossing, and abnormal hairline. These conditions are caused by recessive mutations in members of the aristaless gene family, resulting in abnormal cranial neural crest migration and differentiation. We report a family with a dominantly inherited craniofacial phenotype comprised of frontal bossing with high hairline, ptosis, hypertelorism, broad nasal tip, large anterior fontanelle, cranial base anomalies, and sagittal synostosis. Chromosomal microarray identified a heterozygous 108.3 kilobase deletion of chromosome 2p21 segregating with phenotype and limited to the sine oculis homeobox gene SIX2 and surrounding noncoding DNA. Similar to the human SIX2 deletion phenotype, one mouse model of frontonasal dysplasia, brachyrrhine, exhibits dominant inheritance and impaired cranial base chondrogenesis associated with reduced Six2 expression. We report the first human autosomal dominant frontonasal dysplasia syndrome associated with SIX2 deletion and with phenotypic similarities to murine models of Six2 Loss-of-function.

• 出版日期2016-2