title: Genotypic and phenotypic variation in six patients with solitary median maxillary central incisor syndrome.
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.
authors.affiliation: Department of Oral Health Sciences-Orthodontics, KU Leuven and Dentistry, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Simon
authors.initials: S
authors.lastname: Poelmans
authors.affiliation: Department of Orthodontics and Craniofacial Biology, College of Dentistry, Radboudumc, Nijmegen, The Netherlands.|Department of Maxillofacial Reconstruction and Function, Maxillofacial Orthognathics, Division of Maxillofacial/Neck Reconstruction, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kawamoto
authors.affiliation: Department of Human Genetics, KU Leuven and Centre for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cristofoli
authors.affiliation: Department of Oral and Maxillofacial Surgery, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
authors.forename: Constantinus
authors.initials: C
authors.lastname: Politis
authors.affiliation: Department of Human Genetics, KU Leuven and Centre for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Joris
authors.initials: J
authors.lastname: Vermeesch
authors.affiliation: Department of Oral Health Sciences-Paediatric Dentistry and Special Care, KU Leuven and Dentistry, University Hospitals Leuven, Leuven, Belgium.|Department of Paediatric Dentistry, Paul Sabatier University, Hôpitaux de Toulouse, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bailleul-Forestier
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
authors.forename: Greet
authors.initials: G
authors.lastname: Hens
authors.affiliation: Department of Human Genetics, KU Leuven and Centre for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Koenraad
authors.initials: K
authors.lastname: Devriendt
authors.affiliation: Department of Oral Health Sciences-Orthodontics, KU Leuven and Dentistry, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Anna
authors.initials: A
authors.lastname: Verdonck
authors.affiliation: 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.
authors.forename: Carine
authors.initials: C
authors.lastname: Carels
mesh_terms: D000293:Adolescent; D000848:Anodontia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002872:Chromosome Deletion; D002887:Chromosomes, Human, Pair 18; D002897:Chromosomes, Human, Pair 7; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D005838:Genotype; D053823:Hedgehog Proteins / Q000172:deficiency / Q000235:genetics; D016142:Holoprosencephaly; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007180:Incisor / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008437:Maxilla / Q000002:abnormalities / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics; D055815:Young Adult; D000097607:Homeobox Protein SIX3
chemical_list: D005136:Eye Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D000097607:Homeobox Protein SIX3; C509239:SHH protein, human; C097504:TGIF1 protein, human
keywords: Copy Number Variation (CNV); Exome Sequencing (ES); Holoprosencephaly (HPE); Single Maxillary Median Central Incisor (SMMCI); mutation analysis