Human dentition development is a long and complex process which involves a series of reciprocal and sequential interactions between the embryonic stomodeal epithelium and the underlying neural crest?derived mesenchyme. Despite environment disturbances, tooth development is predominantly genetically controlled. To date, more than 200 genes have been identified in tooth development. These genes implied in various signaling pathways such as the bone morphogenetic protein, fibroblast growth factor, sonic hedgehog homolog, ectodysplasin A, wingless-type MMTV integration site family (Wnt), and transform growth factor pathways. Mutations in any of these strictly balanced signaling cascades may cause arrested odontogenesis and/or other dental defects. This article aims to review current knowledge about the genetic mechanisms responsible for selective nonsyndromic tooth agenesis in humans and to present a detailed summary of syndromes with hypodontia as regular features and their causative genes.

Cochleosaccular dysplasia or degeneration (Scheibe degeneration) is considered the most common cause of profound congenital hearing impairment, and accounts for approximately 70% of cases 2 with hereditary deafness. A five-generation family with hereditary hearing impairment associated with cochleosaccular degeneration has recently been identified. The diagnosis of classical Scheibe degeneration was based on histopathological findings in the temporal bones of the proband, a 61-year-old profoundly deaf male. Auditory structures in the brainstem of the proband were also studied. Twenty-two members of the family were contacted for surveys and blood samples. Of these, 6 males and 2 females have hearing impairment. Complete audiological evaluation was done on 12 family members, and prior audiologic records of the proband and affected family members were available for study. Affected family members suffer a mild bilateral high-frequency hearing loss during childhood and adolescence, and progress to moderate-to-profound deafness in the second and third decades of life. The family is suitable for linkage analysis and does not map to previously reported loci harboring autosomal dominant, nonsyndromic hereditary hearing impairment genes. The genetic study of this family will be helpful in identifying the genes which, when mutated, result in Scheibe degeneration.

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Cancer results from the expansion of cell clones that progressively lose control of proliferation, differentiation, and death, owing to accumulation of mutational events in genes that control the cell cycle and apoptosis. Nuclear protein p53 is thought to play a major role in malignancy, since it induces genes that determine apoptosis and cell-cycle arrest, interacts with proteins employed in DNA repair, and binds to DNA strand breaks. As expected, somatic mutations in p53 are found in a variety of human cancers. Mutations are predominantly inactivating, thus eliminating the "guardian of the genome" from the proliferating cells. Germ-line mutations

Objective: Alterations of the oral microbiome have been associated with obesity, possibly based on inflammatory processes mediated by bacteria. Specific bacterial strains have been associated with obesity and periodontal disease. Little is known about the oral microbiome in children. Understanding the relationship between oral health and childhood growth could help identify preventable factors contributing to obesity and related conditions, including onset of menarche which is associated with obesity. Methods: In this pilot study, we investigated the saliva microbiome among 25 girls 7–15 years old (mean 11.1) and their mothers in an inner city dental clinic in New York City. The main outcome measures were body size, presence or absence of menarche and dental practices. We examined associations of microbiome richness, diversity, and relative abundance with pubertal and demographic factors and oral health. Results: Girls had good dental health and a typical rich oral microbiome, based on the Shannon Index of all species detected. Older girls flossed more often and younger girls had more frequent dental check–ups. Microbiome richness among girls was similar to their mothers’, but diversity was greater among mothers than girls. Richness was reduced among mothers with gum bleeding, flossing and increased teeth brushing. Overweight girls had greater diversity and less richness than normal weight girls. Certain bacterial species differed in abundance with respect to whether girls had reached menarche (Flavobacteria, Actinobacteria), overweight (Megasphaera, Lactorbacillales, Lactobacillus) and gingivitis in the girls (Scardovia, Bifidobacteriales, Gemellaceae). Conclusions: Differences found in specific bacteria in the oral microbiome were related to body size and menarche. With increasing interest on studying microbiome variability related to the multifactorial etiology of obesity in children, saliva is capable of providing clinically informative markers of this and related conditions.

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Waardenburg syndrome (WS) is an autosomal-dominant neural crest cell disorder phenotypically characterized by hearing impairment and disturbance of pigmentation. A presence of dystopia canthorum is indicative of WS type 1, caused by loss of function mutation in the PAX3 gene. In contrast, type 2 WS (WS2) is characterized by normally placed medial canthi and is genetically heterogeneous; mutations in MITF (microphthalmia associated transcription factor) associated with WS2 have been identified in some but not all affected families. Here, we report on a three-generation Indian family with a point mutation in the MITF gene causing WS2. This mutation, initially reported in a Northern European family, creates a stop codon in exon 7 and is predicted to result in a truncated protein lacking the HLH-Zip or Zip structure necessary for normal interaction with its target DNA motif. Comparison of the phenotype between the two families demonstrates a significant difference in pigmentary disturbance of the eye. This family, with the first documented case of two unrelated WS2 families harboring identical mutations, provides additional evidence for the importance of genetic background on the clinical phenotype.

Ellis-van Creveld syndrome (EvC) is a rare autosomal recessive disorder characterized by disproportionate chondrodysplasia, postaxial polydactyly, nail dystrophy, dental abnormalities and in a proportion of patients, congenital cardiac malformations. Weyers acrofacial dysostosis (Weyers) is another dominantly inherited disorder allelic to EvC syndrome but with milder phenotypes. Both disorders can result from loss-of-function mutations in either EVC or EVC2 gene, and phenotypes associated with the two gene mutations are clinically indistinguishable. We present here a clinical and molecular analysis of a Chinese family manifested specific features of EvC syndrome. Sequencing of both EVC and EVC2 identified two novel heterozygous splice site mutations c.384+5G>C in intron 3 and c.1465-1G>A in intron 10 in EVC, which were inherited from mother and father, respectively. In vitro minigene expression assay, RT-PCR and sequencing analysis demonstrated that c.384+5G>C mutation abolished normal splice site and created a new cryptic acceptor site within exon 4, whereas c.1465-1G>A mutation affected consensus splice junction site and resulted in full exon 11 skipping. These two aberrant pre-mRNA splicing processes both produced in-frame abnormal transcripts that possibly led to abolishment of important functional domains. To our knowledge, this is the first report of EVC mutations that cause EvC syndrome in Chinese population. Our data revealed that EVC splice site mutations altered splicing pattern and helped elucidate the pathogenesis of EvC syndrome.