Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, Single Maxillary Median Central Incisor (SMMCI), Holoprosencephaly (HPE), Copy Number Variation (CNV), Exome Sequencing (ES), mutation analysis, 7Q TERMINAL DELETION, CLINICAL SPECTRUM, TOOTH DEVELOPMENT, MIDLINE DEFECTS, SMMCI SYNDROME, SHORT STATURE, SIX3 GENE, MUTATION, DUPLICATION, MONOSOMY, Adolescent, Anodontia, Child, Chromosome Deletion, Chromosomes, Human, Pair 18, Chromosomes, Human, Pair 7, Comparative Genomic Hybridization, DNA Copy Number Variations, Eye Proteins, Female, Genetic Association Studies, Genetic Heterogeneity, Genotype, Hedgehog Proteins, Holoprosencephaly, Homeodomain Proteins, Humans, Incisor, Male, Maxilla, Mutation, Nerve Tissue Proteins, Phenotype, Repressor Proteins, Young Adult, Homeobox Protein SIX3, 0604 Genetics, 1103 Clinical Sciences, 3105 Genetics, 3202 Clinical sciences

Abstract:

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.