title: Dental developmental abnormalities in a patient with subtelomeric 7q36 deletion syndrome may confirm a novel role for the SHH gene.
abstract: Studies in mice demonstrated that the Shh gene is crucial for normal development of both incisors and molars, causing a severe retardation in tooth growth, which leads to abnormal placement of the tooth in the jaw and disrupted tooth morphogenesis. In humans the SHH gene is located on chromosome 7q36. Defects in its protein or signaling pathway may cause holoprosencephaly spectrum, a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres and that can be manifested in microforms such as single maxillary central incisor. A novel role for this gene in the developing human primary dentition was recently demonstrated. We report a 12-year old boy with a de novo 7q36.1-qter deletion characterized by high-resolution karyotyping, oligonucleotide aCGH and FISH. His phenotype includes intellectual disability, non-verbal communication, hypospadia, partial sacral agenesis and absence of coccyx, which are distinctive features of the syndrome and mainly correlated with the MNX1, HTR5A and EN2 genes. No microforms of holoprosencephaly spectrum were observed; but the patient had diastema and dental developmental abnormalities, such as conical, asymmetric and tapered inferior central incisors. The dental anomalies are reported herein for the first time in subtelomeric 7q36 deletion syndrome and may confirm clinically a novel role for the SHH gene in dental development.
authors.affiliation: Setor de Citogenética/Laboratório Central do Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Natália D
authors.initials: ND
authors.lastname: Linhares
authors.affiliation: Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Marta
authors.initials: M
authors.lastname: Svartman
authors.affiliation: Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Mauro Ivan
authors.initials: MI
authors.lastname: Salgado
authors.affiliation: Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Tatiane C
authors.initials: TC
authors.lastname: Rodrigues
authors.affiliation: Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Silvia S
authors.initials: SS
authors.lastname: da Costa
authors.affiliation: Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Rosenberg
authors.affiliation: Departamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Eugênia R
authors.initials: ER
authors.lastname: Valadares
keywords: 7q deletion; ASD, autism spectrum disorder; BERA, brainstem evoked response audiometry; CNV, copy number variation; Comparative genomic hybridization; FISH, fluorescence in situ hybridization; Human EN2 protein; Human HTR5A protein; Human MNX1 protein; Human SHH protein; OFC, occipitofrontal circumference; aCGH, array comparative genomic hybridization