Genetic heterogeneity in X-linked amelogenesis imperfecta

Aldred, Michael J.; Crawford, P. J. M.; Roberts, E. E.; Gillespie, Catherine M.; Thomas, Nicholas Stuart Tudor; Fenton, I.; Sandkuijl, Lodewijk A.; Harper, Peter S.

doi:10.1016/s0888-7543(05)80153-3

Cited by 69 publications

(31 citation statements)

References 16 publications

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“…The effects of these mutations on amelogenin function and the mineralization process remain essentially unknown. Interestingly, the Al trait may also be linked in one kindred to the Xq 22-28 region that is not associated with the AMEL X gene, although cytogenetic studies have not excluded a chromosomal re-arrangement (Aldred et al, 1992a). Recently, autosomal-dominant hypoplastic Al has been linked to chromosome 4q21, providing the first genomic location for an autosomally inherited Al type (Backman et al, 1994;Forsman et al, 1994).…”

Section: Genetic Conditions Affecting Enamelmentioning

confidence: 99%

The Impact of Molecular Genetics on Oral Health Paradigms

Hart

Marazita

Wright

2000

Critical Reviews in Oral Biology & Medicine

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As a result of our increased understanding of the human genome, and the functional interrelationships of gene products with each other and with the environment, it is becoming increasingly evident that many human diseases are influenced by heritable alterations in the structure or function of genes. Significant advances in research methods and newly emerging partnerships between private and public sector interests are creating new possibilities for utilization of genetic information for the diagnosis and treatment of human diseases. The availability and application of genetic information to the understanding of normal and abnormal human growth and development are fundamentally changing the way we approach the study of human diseases. As a result, the issues and principles of medical genetics are coming to bear across all disciplines of health care. In this review, we discuss some of the potential applications of human molecular genetics for the diagnosis and treatment of oral diseases. This discussion is presented in the context of the ongoing technological advances and conceptual changes that are occurring in the field of medical genetics. To realize the promise of this new molecular genetics, we must be prepared to foresee the possibilities and to incorporate these newly emergent technologies into the evolving discipline of dentistry. By using examples of human conditions, we illustrate the broad application of this emerging technology to the study of simple as well as complex genetic diseases. Throughout this paper, we will use the following terminology: Penetrance In a population, defined as the proportion of individuals posessing a disease-causing genotype who express the disease phenotype. When this proportion is less than 100%, the disease is said to have reduced or incomplete penetrance. Polymerase chain reaction (PCR)-A technique for amplifying a large number of copies of a specific DNA sequence flanked by two oligonucleotide primers. The DNA is alternately heated and cooled in the presence of DNA polymerase and free nucleotides, so that the specified DNA segment is denatured, hybridized with primers, and extended by DNA polymerase. MIM-Mendelian Inheritance in Man catalogue number from V. McKusick's Mendelian Inheritance in man (OMIM, 1998).

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Section: Genetic Conditions Affecting Enamelmentioning

confidence: 99%

The Impact of Molecular Genetics on Oral Health Paradigms

Hart

Marazita

Wright

2000

Critical Reviews in Oral Biology & Medicine

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“…AI can be inherited as an autosomal dominant, autosomal recessive or X-linked trait. 1,2 Mutations have been identified in the amelogenin gene, AMGX (locus designated AIH1), on Xp22.1-22.3 in X-linked pedigrees. 3 There is also a second locus on the X chromosome at Xq22-28 (AIH3).…”

Section: Introductionmentioning

confidence: 99%

“…3 There is also a second locus on the X chromosome at Xq22-28 (AIH3). 2,4 The only known locus for autosomal dominant AI to date (AIH2) is on chromosome 4q 5 and the gene mutated in AI at this locus, enamelin, has recently been identified. 6 Prior to this study, no locus had been reported for autosomal recessive AI, though pedigrees suggesting its existence have been documented.…”

Section: Introductionmentioning

confidence: 99%

Identification of a locus on chromosome 2q11 at which recessive amelogenesis imperfecta and cone-rod dystrophy cosegregate

et al. 2002

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A consanguineous Arab pedigree in which recessive amelogenesis imperfecta (AI) and cone-rod dystrophy cosegregate, was screened for linkage to known retinal dystrophy and tooth abnormality loci by genotyping neighbouring microsatellite markers. This analysis resulted in linkage with a maximum lod score of 7.03 to the marker D2S2187 at the achromatopsia locus on chromosome 2q11, and haplotype analysis placed the gene(s) involved in a 2 cM/5 Mb interval between markers D2S2209 and D2S373. The CNGA3 gene, known to be involved in achromatopsia, lies in this interval but thorough analysis of its coding sequence revealed no mutation. Furthermore, affected individuals in four consanguineous recessive pedigrees with AI but without CRD were heterozygous at this locus, excluding it as a common cause of non-syndromic recessive AI. It remains to be established whether this pedigree is segregating two closely linked mutations causing disparate phenotypes or whether a single defect is causing pathology in both teeth and eyes.

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“…A 5kb deletion spanning exons 3-7 of the AMGX gene has been identified in a patient with predominantly hypomaturation A1 (Lagerstrom et al, 1991;Lagerstrom-Fermer et al, 1993), and a single base deletion has been identified in two different families with combined clinical phenotypes of enamel hypomaturation and hypoplasia (Aldred et al, 1992b;Lench et al, 1994). Genetic heterogeneity in X-linked A1 has also been implicated by genetic linkage; a second locus (AIH3) has been mapped to the long arm of the X chromosome (Xq22-q28) (Aldred et al, 1992a). We have studied the AMGX gene in three families exhibiting X-linked A1 using single-strand conformational polymorphism (SSCP) analysis and DNA sequencing of PCR products.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of molecular defects in X-linked amelogenesis imperfecta (AIH1)

1995

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Amelogenins are an heterogenous family of proteins produced by ameloblasts of the enamel organ during tooth development. Disturbances of enamel formation occur in amelogenesis imperfecta, a clinically heterogenous group of inherited disorders characterised by defective enamel biomineralisation. An amelogenin gene, AMGX, has been mapped to the short of the X chromosome (Xp22.1-p22.3) and has been implicated in the molecular pathology of X-linked amelogenesis imperfecta (AIH1). We have identified three families exhibiting AIH1 and screened the AMGX gene for mutations using single-strand conformational polymorphism analysis and DNA sequencing. Three novel mutations were identified: a C-T substitution in exon 5, and a G-T substitution and single cytosine deletion in exon 6, confirming the existence of extensive allelic heterogeneity in this condition. The identification of family-specific mutations will enable early identification of affected individuals and correlation of clinical phenotype with genotype will facilitate an objective system of disease classification.

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Genetic heterogeneity in X-linked amelogenesis imperfecta

Cited by 69 publications

References 16 publications

The Impact of Molecular Genetics on Oral Health Paradigms

The Impact of Molecular Genetics on Oral Health Paradigms

Identification of a locus on chromosome 2q11 at which recessive amelogenesis imperfecta and cone-rod dystrophy cosegregate

Characterisation of molecular defects in X-linked amelogenesis imperfecta (AIH1)

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