Biomedical subjects

M L Marazita

Publications and source records attributed to M L Marazita.

At least 19 recordsLinked to original sources

PubMed2026

Genomic basis of developmental defects of enamel and sex-specific effects.

We conducted a multi-ancestry genome-wide association study (GWAS) of developmental defects of enamel (DDE) in the primary dentition among 6,061 U.S. preschool-aged children (3-5 years). We investigated four DDE phenotypes (demarcated opacities, diffuse opacities, hypoplastic defects, and a combined DDE trait) leveraging main-effect models, joint gene-sex interaction testing (2df), and sex-stratified analyses. SNP-based heritability for the combined DDE trait was estimated at 20%, with concordance analyses robustly supporting a genetic etiology. We identified 39 unique genome-wide significant loci (P<5×10 ), with five surpassing a study-wide Bonferroni-corrected statistical significance criterion (P<1.25×10 9), including Y RNA and ALDH1A1. The main-effect GWAS identified 20 loci, including HBS1L and MYB, genes regulating hematopoiesis with plausible roles in amelogenesis. Joint test and sex-stratified analyses revealed 19 additional loci, including ALDH1A1, TENM2, and DLGAP2, demonstrating sex-specific heterogeneity. Nineteen loci exhibited sex-specific differences after Bonferroni correction (P<2x10-3), including genes involved in retinoic acid signaling (ALDH1A1), odontogenesis (TENM2), and neurodevelopment (DLGAP2, CDH10). Pathway enrichment highlighted ectodermal and synapse organization networks, suggesting shared etiological mechanisms between DDE and systemic conditions like neurofibromatosis and autism spectrum disorder. Notably, no locus generalized in an external GWAS of permanent dentition DDE, underscoring fundamental biological differences in the genetic architectures governing primary versus permanent enamel formation. Crucially, a comprehensive cross-trait pleiotropy lookup against early childhood caries (ECC) revealed no shared genetic architecture, supporting the notion that the established clinical and epidemiological association between DDE and ECC is likely driven by structural defects increasing caries lesion susceptibility rather than genetic pleiotropy. By integrating gene-sex interaction testing, this study offers novel insights into the complex, sexually dimorphic genetic etiology of DDE and augments the biological evidence base that can support the development of precision pediatric dentistry.

developmental defects of enamel↗

PubMed2026

Genetic-epigenetic interactions (meQTLs) in orofacial clefts etiology.

Understanding how genetic variants influence disease risk through molecular mechanisms remains a central challenge in complex disease genetics. Nonsyndromic orofacial clefts (OFCs) exemplify this challenge, with most risk loci residing in non-coding regions. We hypothesized that common genetic variants influence OFC risk by modulating DNA methylation at regulatory elements through methylation quantitative trait loci (meQTLs). We analyzed 10 OFC-associated SNPs against genome-wide DNA methylation profiles in 409 cases and 456 controls, identifying 23 potential meQTLs. Findings were validated using 358 cleft-discordant sibling pairs with MethyLight assays. We performed formal mediation analysis, genotype-tissue interaction and cross-referenced with the mQTL Database to assess developmental timing. Nine meQTLs were validated, including rs987525 (8q24)-cg16561172 (MYC) (P = 9.6 × 10⁻⁶), which mapped to a mesendoderm-active enhancer upstream of MYC. Genotype × tissue interaction confirmed tissue-specificity (P = 1.00 × 10- 3), with stronger effects in oral-derived tissue (saliva). Additional validated SNP-CpG associations involved MAFB-PLCG1, NOG-PPM1E, FOXE1-FRZB, and SPRY2-LGR4. While effect sizes correlated between tissues (r = 0.81), formal mediation analysis indicated individual CpG sites do not fully mediate SNP-phenotype relationships, suggesting coordinated epigenetic mechanisms. Most associations showed peak effects during childhood, while 8q24 showed unique adult-specific patterns. We identified genetic variants influencing methylation at craniofacial regulatory elements, and provided a mechanistic link for a major risk locus, 8q24, with tissue-specific effects in saliva. While individual CpG sites did not fully mediate the genetic risk, our findings identified specific regulatory regions where coordinated epigenetic changes may contribute to OFC susceptibility.

Humans↗

PubMed2025

Genetic-epigenetic interactions (meQTLs) in orofacial clefts etiology.

OBJECTIVES: Nonsyndromic orofacial clefts (OFCs) involve complex genetic and environmental factors, with over 60 risk loci accounting for only a minority of estimated heritability and residing in non-coding regions with unclear functional relevance. We hypothesize that some genetic variants alter orofacial cleft risk by modifying DNA methylation (DNAm) at regulatory sequences essential for craniofacial development, acting as methylation quantitative trait loci (meQTLs). METHODS: We analyzed 10 well-established OFC-associated SNPs against genome-wide DNAm profiles in 409 cases and 456 controls, identifying 23 potential meQTLs. We validated findings using 358 cleft-discordant sibling pairs analyzed with quantitative MethyLight assays. Cross-referencing with the mQTL Database assessed temporal patterns across human development. Functional annotation used GeneHancer and craniofacial enhancer databases. RESULTS: Nine meQTLs were successfully replicated, including the highly significant rs987525 (8q24) - cg16561172 (MYC) association (P = 9.610E-6). This association mapped to a mesendoderm-active enhancer upstream of MYC, providing mechanistic explanation for the longstanding 8q24 cleft locus. Additional validated associations involved MAFB-PLCG1, NOG-PPM1E, FOXE1-FRZB, and SPRY2-LGR4 interactions. Independent differential methylation analysis revealed significant differences between discordant siblings at three CpG sites. Cross-referencing confirmed concordance with population-level methylation effects, with childhood representing the critical developmental window for most associations. CONCLUSIONS: This systematic meQTL characterization in OFCs demonstrates that genetic variants influence disease risk through epigenetic mechanisms. The 8q24-MYC regulatory pathway evidence provides crucial mechanistic insight into a major OFC risk locus. These findings bridge genetic associations with functional consequences, address missing heritability challenges, and suggest potential biomarkers and therapeutic targets for OFC prevention and treatment.

Journal Article↗

PubMed2006

Parental craniofacial morphology in cleft lip with or without cleft palate as determined by cephalometry: a meta-analysis.

OBJECTIVE: To integrate findings from previous cephalometric studies comparing the craniofacial complex of unaffected parents with cleft lip with or without cleft palate (CL/P) children to controls with no history of the disease. DESIGN: Meta-analysis of case-control cephalometric data. INCLUSION CRITERIA: Studies were selected if the unaffected parents of children with CL/P were included and were not combined with parents of children with isolated CP; quantitative data were obtained through cephalometry; the cephalometric variables used were not unique to a study; a case-control design was used; and the means and standard deviations for all variables were reported or could be calculated for both the experimental and the control group. OUTCOME MEASURE: Using raw data obtained from nine studies, mean weighted effect sizes with 95% confidence intervals were calculated for 28 cephalometric variables (mothers and fathers combined) or 18 variables (mothers and fathers separately). Heterogeneity statistics for the effect sizes were also calculated. RESULTS: In general, unaffected parents of children with CL/P possessed significantly wider interorbital, nasal cavity and upper facial dimensions, narrower cranial vaults, longer cranial bases, longer and more protrusive mandibles, shorter upper faces and longer lower faces compared with controls. Increased width of the nasal cavity was the most robust finding. Significant effect size heterogeneity was observed in roughly half of the variables examined. CONCLUSION: Unaffected parents of children with CL/P are characterized by a suite of consistent, yet subtle, craniofacial differences, which could indicate an underlying genetic liability.

Case-Control Studies↗

PubMed2006

Contributions of PTCH gene variants to isolated cleft lip and palate.

OBJECTIVE: Mutations in patched (PTCH) cause the nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin syndrome. Nevoid basal cell carcinoma syndrome may present with developmental anomalies, including rib and craniofacial abnormalities, and predisposes to several tumor types, including basal cell carcinoma and medulloblastoma. Cleft palate is found in 4% of individuals with nevoid basal cell carcinoma syndrome. Because there might be specific sequence alterations in PTCH that limit expression to orofacial clefting, a genetic study of PTCH was undertaken in cases with cleft lip and/or palate (CL/P) known not to have nevoid basal cell carcinoma syndrome. RESULTS: Seven new normal variants spread along the entire gene and three missense mutations were found among cases with cleft lip and/or palate. One of these variants (P295S) was not found in any of 1188 control samples. A second variant was found in a case and also in 1 of 1119 controls. The third missense (S827G) was found in 5 of 1369 cases and in 5 of 1104 controls and is likely a rare normal variant. Linkage and linkage desequilibrium also was assessed using normal variants in and adjacent to the PTCH gene in 220 families (1776 individuals), each with two or more individuals with isolated clefting. Although no statistically significant evidence of linkage (multipoint HLOD peak = 2.36) was uncovered, there was borderline evidence of significant transmission distortion for one haplotype of two single nucleotide polymorphisms located within the PTCH gene (p = .08). CONCLUSION: Missense mutations in PTCH may be rare causes of isolated cleft lip and/or palate. An as yet unidentified variant near PTCH may act as a modifier of cleft lip and/or palate.

Adenine↗

PubMed2005

Tuftelin, mutans streptococci, and dental caries susceptibility.

The purpose of this study was to identify genetic factors that contribute to dental caries susceptibility, either alone or in combination with environmental factors. Dental examinations were performed and buccal swab samples collected from 3- to 5-year-old children with at least 4 surfaces of decay, or with no evidence of decay. SNP assays for each of 6 candidate genes were performed for all cases and controls. Chi-square analysis and regression analysis were used for the evaluation of individual gene effects, environmental effects, and gene-environment interactions. There were no significant associations between single candidate genes and caries susceptibility. Levels of S. mutans were positively and Lactobacilli were negatively associated with caries. Regression analysis revealed a significant interaction between tuftelin and S. mutans, with 26.8% of the variation in dmfs explained by the interaction. Future research will focus on the identification of these additional factors and the development of functional assays so that these interactions can be better understood.

Chi-Square Distribution↗

PubMed2004

Targeted scan of fifteen regions for nonsyndromic cleft lip and palate in Filipino families.

Cleft lip with or without cleft palate (CL/P) is a congenital anomaly with variable birth prevalence based on geographic origins, with the highest rates commonly found in Asian populations. About 70% of cases are nonsyndromic (NS), in which the affected individual has no other abnormalities. NS CL/P is a complex disorder with genetic and environmental effects and no specific genetic loci yet confirmed. Fifteen candidate regions were examined for linkage to NS CL/P. Regions were chosen based on previous suggestive linkage and/or association in human families, or suggestive animal model data. Polymorphic markers in these regions were genotyped for analysis on 36 Filipino families comprised of 126 affected and 218 unaffected individuals. An additional 70 families with 149 affecteds were used for replication of suggestive results. Parametric (LOD score) and nonparametric (SIMIBD) linkage analyses were performed as well as transmission disequilibrium test (TDT) analysis. Five markers yielded suggestive results from the 36 families. The parametric LOD scores for the MSX1-CA and D4S1629 were >1.0 and the SIMIBD P values for D6S1029 and RFC1 are suggestive (<0.06), while the SIMIBD P value of 0.01 for TGFA was significant. Since the Msx1 mouse knockout has cleft palate and MSX1 mutations have been found in rare cases of syndromic CL/P, this locus is especially plausible for linkage. Previous studies have also found linkage of NS CL/P to 4q31 and 6p23. These regions contain several candidate genes, including AP2 at 6p23 and FGF2, BMPR1B, and MADH1 at 4q31. TGFA has both linkage and linkage disequilibrium data supporting it as a candidate gene for NS CL/P. While no region was definitively confirmed for linkage to NS CL/P, the data do support further investigation using larger sample sizes and candidate gene studies at 2p13.2, 4p16.2, 4q31, 6p23, and 16q22-24.

Chromosome Mapping↗

PubMed2004

TP63 mutation and clefting modifier genes in an EEC syndrome family.

Autosomal dominant EEC syndrome consists of ectrodactyly, ectodermal dysplasia, and cleft lip with or without cleft palate (CL/P). We investigated an EEC kindred with 10 affected persons in three generations in order to map the causative mutation in this family and to map modifier genes that contribute to the expression of facial clefting in the phenotype. DNA from 15 family members was genotyped for 388 genome screen markers. Analysis revealed maximal linkage between EEC and chromosome 3q27, which contains a known EEC gene - tumor protein 63 (TP63). Sequencing showed a CGT-->TGT missense mutation (R280C) in exon 7, previously reported to cause EEC in four families, and ectrodactyly alone (split hand-foot malformation) in one sporadic case and one large kindred. Analysis of the clefting phenotype in this EEC family demonstrated maximal linkage to two regions on chromosomes 4q and 14, which multiple studies have implicated in non-syndromic CL/P. In conclusion, this study demonstrates that the mutation of TP63 is the major (Mendelian) EEC gene in this kindred and suggests that additional minor modifying genes which predispose to non-syndromic CL/P could also contribute to the expression of the clefting component of the syndrome in this family.

Abnormalities, Multiple↗

PubMed2003

Sequence variations in CREB1 cosegregate with depressive disorders in women.

Major depressive disorder (MDD) constitutes a major public health problem worldwide and affects women twice as frequently as men. Previous linkage studies have identified a 451 kb region of 2q33-35 that exhibited significant evidence of linkage to Mood Disorders among women (but not men) from families with recurrent, early-onset MDD (RE-MDD), a severe and strongly familial subtype of MDD. This 451 kb region includes CREB1, an attractive susceptibility gene for MDD and related disorders. Sequence variations in the CREB1 promoter and intron 8 have been detected that cosegregate with Mood Disorders, or their absence, in women from these families, identifying CREB1 as a sex-limited susceptibility gene for unipolar Mood Disorders. These findings implicate the cAMP signaling pathway in the pathophysiology of Mood Disorders and related conditions.

Cyclic AMP↗

PubMed2003

MSX1 and TGFB3 contribute to clefting in South America.

MSX1 and TGFB3 have been proposed as genes in which mutations may contribute to non-syndromic forms of oral clefts; however, an interaction between these genes has not been described. The present study attempts to detect transmission distortion of MSX1 and TGFB3 in 217 South American children from their respective mothers. With transmission disequilibrium test analysis, cleft lip with/without cleft palate, cleft lip with palate plus cleft palate only, and all datasets combined showed evidence of association with MSX1 (p = 0.004, p = 0.037, and p = 0.001, respectively). With likelihood ratio test analysis, "cleft lip only" showed association with MSX1 (p = 0.04) and "cleft palate only" with TGFB3 (p = 0.02). A joint analysis of MSX1 and TGFB3 suggested that there may be an interaction between these two loci to increase cleft susceptibility. These results suggest that MSX1 and TGFB3 mutations make a contribution to clefts in South American populations.

Alleles↗

PubMed2003

Segregation analysis of mandibular prognathism in Libya.

The etiology of mandibular prognathism has been attributed to various genetic inheritance patterns and some environmental factors. The variation in inheritance patterns can be partly due to the use of different statistical approaches in the respective studies. The objective of this study was to investigate the role of genetic influences in the etiology of this trait. We performed segregation analysis on 37 families of patients currently being treated for mandibular prognathism. Mandibular prognathism was treated as a qualitative trait, with cephalometric radiographs, dental models, and photographs used to verify diagnosis. Segregation analysis of a prognathic mandible in the entire dataset supported a transmissible Mendelian major effect, with a dominant mode of inheritance determined to be the most parsimonious.

Adult↗

PubMed2002

Cleft lip with or without cleft palate and dermatoglyphic asymmetry: evaluation of a Chinese population.

OBJECTIVE: To determine if Chinese individuals with non syndromic cleft lip with or without cleft palate (CL/P) display more dermatoglyphic asymmetry than unaffected relatives or controls. DESIGN: Case-control study with two control groups (genetically related and unrelated). SETTING AND SAMPLE POPULATION: A total of 500 CL/P probands from Shanghai, China, 421 unaffected relatives, and 66 controls of Chinese heritage. METHODS: Finger and palm prints were collected, and pattern frequencies, total ridge counts (TRC), and atd angles were calculated. Asymmetry scores between right and left hands were defined for each of the three dermatoglyphic measures. Probands' asymmetry scores were compared statistically with the scores of unaffected relatives and controls. RESULTS: In general, the probands' asymmetry scores for TRC and atd angle did not differ significantly from the scores of either unaffected relatives or controls. However, probands with a positive family history of clefting showed significantly more asymmetry in their pattern types than either probands without a family history, unaffected relatives or controls. CONCLUSION: These results suggest that a unique genetic mechanism of developmental instability may obtain in CL/P individuals with a positive family history of clefting.

Analysis of Variance↗

PubMed2002

Epidemiological and genetic study of 121 cases of oral clefts in Kuwait.

AIM: The aim of the study was to ascertain some epidemiological factors such as sex and consanguinity that may be associated with cleft lip with or without cleft palate (CL +/- CP) in Kuwait as well as to conduct genetic segregation analysis of these families. SETTING AND SAMPLE POPULATION: A total of 113 families ascertained through 121 CL +/- CP and CP surgical probands in Kuwait. The frequencies of cleft types and the epidemiological variables were calculated using SPSS version 5.0 software. Chi-square for goodness-of-fit test was used to test the significance of the associated epidemiological variables to facial clefts. Genetic segregation analysis was performed on 76 families with extended pedigrees and included only those with non-syndromic CL +/- CP (NS CL +/- CP). Major locus segregation analysis was used to fit models to the observed family patterns under Class A regressive models as implemented by REGD routine in S.A.G.E. release 4.0. A test for heterogeneity was also conducted to complete data set in addition to two subsets: Arabs and nomads. RESULTS: Of the 121 patients, 34(28.1%) had CP, 30(24.8%) had CL and 57 (47.1%) had CL + CP. The male to female ratio was 0.89 for CP, 1.14 for CL, 1.35 for CL + CP and 1.2 for all the clefts. The percentage of consanguineous families among those with a positive family history (60%) was not significantly different from that of the general population (54.3%), whereas for all the families with clefts the percent consanguineous was significantly lower (38%). No evidence of heterogeneity in the results between the Arab and nomad subsets was observed. The results for the major locus segregation analysis were inconclusive. CONCLUSION: No definite association was observed between consanguinity and the occurrence of facial clefts in Kuwait. General transmission models in the full data set showed no evidence of heterogeneity in the results between the Arab and nomad subsets.

Adolescent↗

PubMed2001

Case/control family study of autonomic nervous system dysfunction in idiopathic congenital central hypoventilation syndrome.

Children with idiopathic congenital central hypoventilation syndrome (CCHS) have a complex phenotype consistent with an imbalance of the autonomic nervous system (ANS). Since CCHS may be genetic in origin, we hypothesized that relatives of individuals with CCHS may exhibit symptoms of ANS dysfunction (ANSD), albeit in a milder form. We tested this hypothesis by assessing aspects of ANS function in relatives of CCHS cases vs. relatives of matched controls with a scripted questionnaire. Only those 35 symptoms of ANSD exhibited by > or =5% of the CCHS cases were included in the analysis as the basis for determining ANSD affection status. Two different arbitrary ANSD affection status definitions are presented in detail: any case, control, or relative with positive findings (1) in two or more symptoms, or (2) in two or more systems. The subjects included in the analysis totaled 2,353, including 56 CCHS cases, 56 age-, gender-, and race-matched controls, and their families. Under each of the two arbitrary ANSD affection statuses, CCHS cases and parents of cases were more likely to be affected than controls and parents of controls (P < 0.001 for both comparisons), 16% of the CCHS siblings had the ANSD phenotype with two or more symptoms, compared to 4% of control siblings (P = 0.03). Aunts and uncles of the CCHS cases were also significantly more likely to have two or more ANSD symptoms than were aunts and uncles of the controls (P= 0.009). These results support our hypothesis and also indicate that relatives of the CCHS cases tended to manifest a milder spectrum of ANSD, with fewer systems and/or fewer symptoms than the cases.

Autonomic Nervous System Diseases↗

PubMed2001

Genetic segregation analysis of autonomic nervous system dysfunction in families of probands with idiopathic congenital central hypoventilation syndrome.

Idiopathic congenital central hypoventilation syndrome (CCHS) is a very rare syndrome with major respiratory complications. Hypothesizing that CCHS is the most severe manifestation of general autonomic nervous system dysfunction (ANSD), we applied a case-control family study design to investigate the genetics of ANSD. Fifty-two probands with CCHS were identified, as well as 52 age-, race-, and gender-matched controls. ANSD phenotypic features were characterized in the cases, controls, and their family members. Our earlier studies found that most ANSD symptoms were more likely in CCHS cases and their relatives than in controls and their relatives (P < 0.05). The goal of the current study was to determine if the familiality of ANSD was consistent with a genetic pattern. We performed major locus segregation analysis of ANSD utilizing regressive models. CCHS probands were assumed to be affected; controls and relatives were designated as affected if they had two or more relevant symptoms. The hypothesis of "no transmission and no familial effects" was rejected in both case and control families. Case families were consistent with transmission of a major effect; control families were not (the difference in the pattern of results was significant, P < 0.0001). In the total data set, the best-fitting model was codominant Mendelian inheritance of a major gene for ANSD. These case-control family studies support our hypothesis that CCHS is the most severe manifestation of a general ANSD, with a family pattern consistent with Mendelian transmission, and demonstrate the potential utility of the approach to studies of other, similarly intractable disorders.

Abnormalities, Multiple↗

PubMed2001

Quantitative trait linkage analysis of the liability underlying a common oligogenic disease.

We utilized pedigree discriminant and factor analytic approaches to combine multivariate phenotypic information into a single liability phenotype in the isolate and general populations. We applied two-stage relative-pair quantitative trait linkage analysis to detect genetic contributions to variation in the resulting liability phenotypes. Linkage analysis revealed several regions of suggestive linkage in both the general and isolate populations, the majority of which appear in retrospect to be false positives. A likely explanation is an overall lack of power given that we tested hypotheses in data from only one replicate. However, it may be possible that a construct that ignores affection status when using liability-associated characteristics as indicators of this construct is not the most effective approach in modeling the liability underlying a complex phenotype.

Chromosome Mapping↗

PubMed2001

Social anxiety in Chinese adults with oral-facial clefts.

OBJECTIVE: This study examined social anxiety and measures of psychosocial adjustment in Chinese adults with oral-facial clefts, their unaffected siblings, and age-matched controls. DESIGN: This cross-sectional study utilized a matched case-control study design. PARTICIPANTS: Eighty-five adult cleft lip and cleft palate (CL/CP) subjects and 85 unaffected siblings (one adult sibling of each CL/CP subject) were recruited in Shanghai, China, from a larger CL/CP study. Eighty-five unaffected controls, gender- and age-matched to the CL/CP subjects, were recruited from Shanghai work units including factories, universities, and other institutions. OUTCOME MEASURES: Social Avoidance and Distress Scale, Fear of Negative Evaluation, Rosenberg Self-Esteem Scale, Interpersonal Support Evaluation List. RESULTS: Affected adults reported significantly more social anxiety than unaffected siblings and controls. Affected adults also scored significantly lower on measures of self-esteem and social support than unaffected siblings and controls. Unaffected siblings and controls were not found to differ on any of these measures. CONCLUSIONS: Findings suggest that individuals with oral-facial clefts may be more disadvantaged with respect to social affiliation and adaptation than unaffected adults. Cross-cultural research is essential in enabling us to determine whether similar trends exist across cultures.

Adult↗

PubMed2000

Localisation of a gene for prepubertal periodontitis to chromosome 11q14 and identification of a cathepsin C gene mutation.

Prepubertal periodontitis (PPP) is a rare and rapidly progressive disease of young children that results in destruction of the periodontal support of the primary dentition. The condition may occur as part of a recognised syndrome or may occur as an isolated finding. Both autosomal dominant and recessive forms of Mendelian transmission have been reported for PPP. We report a consanguineous Jordanian family with four members affected by PPP in two nuclear sibships. The parents of the affected subjects are first cousins. We have localised a gene of major effect for PPP in this kindred (Zmax=3.55 for D11S901 at theta=0.00) to a 14 cM genetic interval on chromosome 11q14 flanked by D11S916 and D11S1367. This PPP candidate interval overlaps the region of chromosome 11q14 that contains the cathepsin C gene responsible for Papillon-Lefèvre and Haim-Munk syndromes. Sequence analysis of the cathepsin C gene from PPP affected subjects from this Jordanian family indicated that all were homozygous for a missense mutation (1040A-->G) that changes a tyrosine to a cysteine. All four parents were heterozygous carriers of this Tyr347Cys cathepsin C mutation. None of the family members who were heterozygous carriers for this mutation showed any clinical findings of PPP. None of the 50 controls tested were found to have this Tyr347Cys mutation. This is the first reported gene mutation for non-syndromic periodontitis and shows that non-syndromic PPP is an allelic variant of the type IV palmoplantar ectodermal dysplasias.

Aggressive Periodontitis↗