Academic journal article Iranian Journal of Public Health

Missense Mutation in Fam83H Gene in Iranian Patients with Amelogenesis Imperfecta

Academic journal article Iranian Journal of Public Health

Missense Mutation in Fam83H Gene in Iranian Patients with Amelogenesis Imperfecta

Article excerpt


Amelogenesis imperfecta (AI) is a common group of inherited defects that presentquantitative or qualitative tooth enamel malformation in the absence of systemic manifestations. AI has been classified into syndromic and non-syndromic forms(1). AI is sometimes associated with different syndromes such as tricho-dento-osseous (TDO) syndrome (OMIM #190320) and cone rod dystrophy. According to population-base studies, the incidence of AI varies, from 1 in 700 to 1 in 15,000 (2).

The phenotype of affected individuals is highly variable and can be divided based on whether the abnormality results in a reduced amount of enamel (hypoplasia), deficient calcification (hypocalcification), or deficient maturation of the enamel (hypomaturation) (1, 3). The mineralization level of enamel in the hypomaturation and hypocalcified AI is not normal and can be described as hypomineralized. Its genetic inheritance pattern is reported as either an xlinked or autosomal recessive (AR) or autosomal dominant (AD) (3, 4).

In order to better understand how defective enamel formation occurs through development, two fundamental questions must be addressed (1) which candidate genes are responsible for various forms of AI (2) and how do these candidate genes and their protein partners work together in normal and abnormal enamel formation? So far, changes in several ameloblast specific genes have been detected including Amelogenin (AMELX) (5-7), Ameloblastin (AMBN) (8, 9), Enamelysin (ENAM)(10-17), Kallikrein-related peptidase- 4KLK4(18, 19),Family with sequence similarity 83 (FAM83H) (6, 20-22) and Matrix Metalloproteinase 20 (MMP20)(14, 23-25).

In the present study, we aimed to screen the genetic alterations in the most important candidate genes, ENAM, KLK4, MMP20 and FAM83H responsible for AI in five Iranian families.

Materials & Methods


This study was a case study based on genetic testing of affected patients and healthy people Inclusion criteria for our study were as follows: 1) patients were required to have an isolated form of AI; 2) Patients were included in this study with inheritance patterns.

A total of 50 family members (22 affected and 28 unaffected) from five Iranian families were studied. Five Iranian families with AI were diagnosed at the Pediatric Dentistry Department of Tehran University of Medical Sciences (TUMS).

The study was performed with the approval of the Institutional Review Board (IRB) and informed consent was obtained from each patient and controls before genetic testing. The pedigree analysis was carried out using Cyrillic 2.1 software.

Molecular Analysis

5 ml peripheral blood was collected in test tubes containing 0.5 M EDTA from patients, unaffected members of the family and 100 healthy controls. Then, DNA was extracted using DNGPLUS kit (Cinnagen, Tehran-Iran). The PCR amplification was typically carried out using primer pairs of exon- intron boundaries of ENAM, FAM38H, MMP20 and KLK4 genes (Table 1), 0.2U Taq DNA polymerase (Roche, Mannheim, Germany), 10pmole of each primer, 200 µM of each dNTPs, 0.67µl of 50mM MgCl2, 60ng DNA and 2.5 µl of PCR buffer in 25µl of PCR reactions. The PCR conditions included an initial denaturation step for 3 min at 95°C, 30 sec at 95°C, 45 sec at 64°C with a 1°C decrease every second cycle down to 55°C, then 55°C for 14 cycles, 1 min at 72°C for extension, and finally 10 min at 72°C. PCR products were separated on 2% agarose gels and visualized with ethidium bromide. Subsequently, to determine any mutation the PCR product was subjected to direct sequencing (Gene Fanavaran, Iran). Sequence data searches were performed in nonredundant nucleic and protein databases BLAST (


Clinical descriptions and mutational analysis After clinical examination, affected individuals from one family showed clinical features consistent with ADHCAI (Fig. 1), while 4 consanguineous families with 18 affected members were diagnosed for ARHPAI. …

Search by... Author
Show... All Results Primary Sources Peer-reviewed


An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.