Analysis of gene mutation in a pedigree with autosomal dominant Charcot-Marie-Tooth disease / 南方医科大学学报

OBJECTIVE@#To investigate the molecular genetic mechanism of Charcot- Marie-Tooth (CMT) disease in a pedigree.@*METHODS@#Genomic DNA was extracted from the peripheral blood of the family members of a pedigree with autosomal dominant CMT disease, and 65 candidate genes of the proband were screened using target exon capture and the next generation sequencing, and the suspicious genes were verified using Sanger sequencing. PolyPhen-2, PROVEAN and SIFT software were used to predict the function of the mutant genes, and PyMOL-1 software was used to simulate the mutant protein structure.@*RESULTS@#A heterozygous missense mutation [c.371A>G (p.Y124C)] was detected in exon 3 of gene of the proband. This heterozygous mutation was also detected in both the proband's mother and her brother, but not in her father. Multiple sequence alignment analysis showed that tyrosine at codon 124 of GDAP1 protein was highly conserved. All the 3 prediction software predicted that the mutation was harmful. Molecular structure simulation showed a weakened interaction force between the amino acid residues at codon 124 and the surrounding amino acid residues to affect the overall stability of the protein.@*CONCLUSIONS@#The mutation of gene may be related to the pathogenesis of autosomal dominant AD-CMT in this pedigree. The newly discovered c.371A>G mutation (p.Y124C) expands the mutation spectrum of gene, but further study is needed to clarify the underlying pathogenesis.

A novel HSF4 mutation in a Chinese family with autosomal dominant congenital cataract / 华中科技大学学报（医学）（英德文版）

This study was aimed to identify the mutation of the whole coding region of shock transcription factor 4 (HSF4) gene in a Chinese family with autosomal dominant congenital cataract (ADCC). All exons of HSF4 were amplified by PCR. Sequence analysis of PCR products was performed. Restriction fragment length polymorphism (RFLP) analysis was conducted to confirm the pathogenic mutation. The results showed that a C to T substitution occurred at nucleotide 331 in patients of this family, leading to the replacement of the amino acid arginine-111 with cysteine in exon 3. RFLP analysis showed that the amino acid change was co-segregated with all affected individuals. It was concluded that the new mutation of c.331C>T in HSF4 DNA may be responsible for the autosomal dominant congenital cataract in this family.

Mutation analysis of HOXD13 gene in a Chinese family affected with autosomal dominant synpolydactyly / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutation in a Chinese family affected with autosomal-dominant synpolydactyly and to provide the basis for prenatal diagnosis.</p><p><b>METHODS</b>Inheritance pattern was determined by clinical examination and pedigree analysis. Blood samples were obtained from members of the family. Genomic DNA was extracted and sequenced following PCR amplification. Suspected mutation was confirmed by subclone sequencing and agarose gel electrophoresis.</p><p><b>RESULTS</b>A 27 bp expansion mutation in exon 1 of HOXD13 was identified in all affected individuals from the family but not in unaffected members and normal controls. The mutation has caused insertion of 9 alanines in the polyalanine-expansion region of HOXD13 protein.</p><p><b>CONCLUSION</b>A polyalanine-expansion within the HOXD13 probably underlies the disease in this family.</p>

Analysis of CSF1R gene mutation in a Chinese family with hereditary diffuse leukoencephalopathy with neuroaxonal spheroids / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutation of the colony stimulating factor 1 receptor gene (CSF1R) in a large Chinese family affected with hereditary diffuse leukoencephalopathy with spheroids (HDLS) and analyze the genotype-phenotype correlation.</p><p><b>METHODS</b>The proband was evaluated physically and radiologically to ascertain the HDLS phenotype. Genomic DNA was extracted from peripheral blood samples from family members. The coding region of the CSF1R gene was amplified with PCR and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>There were 9 affected members (5 alive) in this five-generation family (1 member had died during the follow-up). A missense mutation c.2563C>A (p.P855T) of the CSF1R gene has been identified in the proband. The same mutation was identified in 3 affected and 1 unaffected members of the family.</p><p><b>CONCLUSION</b>The family was consistent with autosomal dominant inheritance. CSF1R gene mutation is also a disease-causing mutation in Chinese patients.</p>

Molecular genetic analysis and clinical phenotype of a pedigree with familial dominant drusen / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze clinical features and mutations of EFEMP1 gene in a Chinese pedigree with familial dominant drusen.</p><p><b>METHODS</b>Clinical features of the pedigree were studied with fundus photography, fundus fluorescein angiography and optical coherence tomography. Molecular genetic analysis was performed on the patients and unaffected individuals from the family. All coding exons of the EFEMP1 gene were amplified by polymerase chain reaction (PCR) and sequenced. The results were compared with wild-type sequences from NCBI. The proband who had suffered from choroidal neovascularization and preretinal hemorrhage received an intravitreal injection of an anti-vascular endothelial growth factor (VEGF) preparation.</p><p><b>RESULTS</b>A heterozygous mutation C>T (R345W) was identified in exon 10 of the EFEMP1 gene in two affected individuals from the family. The same mutation was not detected in unaffected family members and 100 healthy individuals. Postoperative follow-up of the patient receiving intravitreal injection of anti-VEGF drug showed that visual acuity was improved and fundus appeared to be stable.</p><p><b>CONCLUSION</b>The R345W mutation in EFEMP1 is responsible for the dominant drusen in this family. Intravitreal injection of anti-VEGF drug is a promising treatment for the improvement in vision.</p>

Sheep gastrointestinal helminthiasis in the Sertão region of Paraíba State, Northeastern Brazil: prevalence and risk factors / Helmintoses gastrintestinais de ovinos no Sertão do Estado da Paraíba, Nordeste do Brasil: prevalência e fatores de riscos

In this study, we aimed to establish the prevalence and risk factors relating to gastrointestinal helminthiasis, and to characterize the sanitary management practiced among sheep herds in the Sertão region of the state of Paraíba, northeastern Brazil, based on factors that condition the ways of controlling these parasites in these herds. The research was carried out between April and July 2012. We visited 54 farms, where fecal and blood samples were individually collected from 465 animals. On each farm, a questionnaire was applied to gather information on variables relating to potential risk factors. The prevalence of sheep gastrointestinal helminthiasis in the region was 75.9%. At least one animal tested positive for this helminthiasis on 53 (98.1%) of the 54 farms evaluated. The eggs per gram of feces (EPG) analysis showed the following infection burdens: 51.8% with mild infection, 27.1% moderate infection, 9.9% heavy infection and 11.2% fatal infection. Among the sheep farms visited, anthelmintics were used on 81.5% (p <0.05). The most relevant risk factor in this study was the farm area, because it defines the area available for grazing animals. Properties with many animals and little pasture area, which are the most abundant type in the Sertão region of Paraíba, tend to have high prevalence of gastrointestinal helminthiasis, because the animals are more prone to reinfection. The Sertão region of Paraíba presents high prevalence of gastrointestinal helminthiasis among sheep, and the farm area is the most relevant risk factor for the development of these parasites.

Objetivou-se determinar a prevalência e os fatores de risco para as helmintoses gastrintestinais, caracterizando o manejo sanitário sob fatores condicionantes das formas de controle dessas parasitoses em rebanhos de ovinos da região do Sertão da Paraíba. A pesquisa foi desenvolvida no período de abril a julho de 2012. Foram visitadas propriedades, utilizando-se 465 animais, sendo coletadas individualmente amostras de fezes e sangue durante as visitas. Em cada propriedade, foi aplicado questionário para a coleta de informações acerca de variáveis que atuariam como possíveis fatores de risco. Observou-se que a prevalência das helmintoses gastrintestinais de ovinos na região do Sertão da Paraíba foi de 75,9%. Pelo menos um animal foi positivo para essas helmintoses, em 53 (98,1%) das 54 propriedades avaliadas. A análise de OPG (Ovos Por Gramas de Fezes) demonstrou que 51,8% dos animais apresentaram infecção leve, 27,1% infecção moderada, 9,9% infecção pesada e 11,2% infecção fatal. A utilização de anti-helmínticos ocorreu em 81,5% das propriedades (p <0,05). O fator de risco mais relevante neste estudo foi a área da propriedade, porque delimita a área de pastejo do animal. Propriedades com muitos animais e pouca área de pastejo, que são as mais abundantes no Sertão da Paraíba, tendem a apresentar alta prevalência de helmintoses gastrintestinais, pois os animais estão mais propensos à reinfecção. A região do Sertão da Paraíba apresenta uma elevada prevalência de helmintoses gastrintestinais em ovinos, e a área das propriedades é o fator de risco mais relevante para o desenvolvimento dessas parasitoses.

Clinical features and management of hereditary spastic paraplegia / Aspectos clinicos e manejo das paraplegias espasticas hereditarias

Hereditary spastic paraplegia (HSP) is a group of genetically-determined disorders characterized by progressive spasticity and weakness of lower limbs. An apparently sporadic case of adult-onset spastic paraplegia is a frequent clinical problem and a significant proportion of cases are likely to be of genetic origin. HSP is clinically divided into pure and complicated forms. The later present with a wide range of additional neurological and systemic features. To date, there are up to 60 genetic subtypes described. All modes of monogenic inheritance have been described: autosomal dominant, autosomal recessive, X-linked and mitochondrial traits. Recent advances point to abnormal axonal transport as a key mechanism leading to the degeneration of the long motor neuron axons in the central nervous system in HSP. In this review we aim to address recent advances in the field, placing emphasis on key diagnostic features that will help practicing neurologists to identify and manage these conditions.

Paraplegias espásticas hereditárias (PEH) constituem um grupo de desordens geneticamente determinadas caracterizadas por espasticidade e paraparesia de progressão insidiosa. Paraplegia espástica aparentemente esporádica de início no adulto constitui problema frequente na prática neurológica. Evidências recentes sugerem que uma proporção significativa destes casos é geneticamente determinada. O grupo das PEH é dividido clinicamente em formas puras e complicadas de acordo com a concomitância de outras manifestações clinicas e neurológicas. Até o momento 60 tipos genéticos foram identificados. Todos os modos de herança monogênica já foram descritos: autossômica dominante, autossômica recessiva, ligada ao X e mitocondrial. Avanços recentes indicam que alterações do transporte axonal estão implicadas na degeneração dos longos axônios motores no sistema nervoso central na PEH. Nesta revisão abordamos recentes avanços na área com ênfase nos aspectos clínicos chave que ajudam o neurologista geral no diagnóstico e manejo correto deste grupo de doenças.

Split-hand/feet malformation in three tamilian families and review of the reports from India.

Split‑hand/foot malformation (SHFM) is a rare condition which can be either syndromic or nonsyndromic. We report three unrelated pedigrees, one with autosomal dominant (AD) inheritance and the other two with autosomal recessive (AR) pattern. We also briefly review the published reports from India.

Autosomal Dominant Type I Osteopetrosis Is Related with Iatrogenic Fractures in Arthroplasty

Autosomal dominant osteopetrosis (ADO) is a sclerotic bone disorder due to failure of osteoclasts. ADO poses difficulties during arthroplasty because of the increased chance for iatrogenic fractures due to sclerotic bone. ADO is divided into two types based on radiological findings, fracture risk, and osteoclast activity. These differences suggest less brittle bone in patients with ADO I compared to that of patients with ADO II, which suggests a smaller chance of preoperative fractures during cementless arthroplasty in ADO I compared with that in ADO II. A case of cementless total knee arthroplasty in a patient with ADO I is presented. Total hip arthroplasty was performed during follow-up, and known major problems related to ADO II were experienced. Therefore, the differences between ADO I and ADO II may not be clinically relevant for an iatrogenic fracture during arthroplasty in patients with ADO.

Deoxyribonucleic acid repair gene X-ray repair cross-complementing group 1 polymorphisms and non-carcinogenic disease risk in different populations: A meta-analysis.

PURPOSE: This study aims to assess a meta‑analysis of the association of X‑ray repair cross‑complementing group 1 (XRCC1) polymorphisms with the risk of various non‑carcinogenic diseases in different population. MATERIALS AND METHODS: This meta‑analysis was performed by critically reviewing reveals 38 studies involving 10043 cases and 11037 controls. Among all the eligible studies, 14 focused on Arg194Trp polymorphism, 33 described the Arg399Gln and three articles investigated on Arg280His. Populations were divided into three different ethnic subgroups include Caucasians, Asians and other (Turkish and Iranian). RESULTS: Pooled results showed no correlation between Arg194Trp and non‑carcinogenic disease. There was only weak relation in the recessive (odds ratio [OR] =1.11, 95% confidence interval [CI]: 0.86‑1.44) model in Asian population and dominant (OR = 1.04, 95% CI: 0.66‑1.63) model of other populations. In Arg399Gln polymorphism, there was no relation with diseases of interest generally. In the pooled analysis, there were weak relation in the dominant (OR = 1.08, 95% CI: 0.86‑1.35) model of Asian population and quite well‑correlation with recessive (OR = 1.49, 95% CI: 1.19‑1.88), dominant (OR = 1.23, 95% CI: 0.94‑1.62), and additive (OR = 1.23, 95% CI: 0.94‑1.62) models of other subgroup. For Arg280His, there was a weak relation only in the dominant model (OR = 1.06, 95% CI: 0.74‑1.51). CONCLUSION: The present meta‑analysis correspondingly shows that Arg399Gln variant to be associated with increased non‑carcinogenic diseases risk through dominant and recessive modes among Iranian and Turkish population. It also suggests a trend of dominant and recessive effect of Arg280His variant in all population and its possible protective effect on non‑carcinogenic diseases.

Mutation in the PCSK9 gene in Omani Arab subjects with autosomal dominant hypercholesterolemia and its effect on PCSK9 protein structure

Proprotein convertase subtilisin/kexin type [PCSK9] is a crucial protein in LDL cholesterol [LDL-C] metabolism by virtue of its pivotal role in the degradation of the LDL receptor. Mutations in the PCSK9 gene have previously been found to segregate with autosomal dominant familial hypercholesterolemia [ADFH]. In this study, DNA sequencing of the 12 exons of the PCSK9 gene has been performed for two patients with a clinical diagnosis of familial hypercholesterolemia where mutation in the LDL-receptor gene hasn't been excluded. One missense mutation was detected in the exon 9 PCSK9 gene in the two ADFH patients. The patients were found to be heterozygote for Ile474Val [SNP rs562556] Using an array of in silico tools, we have investigated the effect of the above mutation on different structural levels of the PCSK9 protein Although, the mutation has already been reported in the literature for other populations, to the best of our knowledge this is the first report of a mutation in the PCSK9 gene from the Arab population, including the Omani population

Clinical features and mutation analysis of CHRNA4 gene for families and sporadic cases affected with autosomal dominant nocturnal frontal lobe epilepsy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate mutations of CHRNA4 gene in Chinese patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).</p><p><b>METHODS</b>Two hundred and fifty-seven patients (including 215 sporadic and 42 familial cases) were analyzed. Mutational screening was performed by sequencing all of the 6 exons of the CHRNA4 gene including the donor and acceptor splice sites.</p><p><b>RESULTS</b>The results have excluded the involvement of any known mutations of the CHRNA4 gene. A novel synonymous mutation c.570C>T(D190D) and 6 single nucleotide polymorphisms (SNPs) of the CHRNA4 gene were detected in 6 sporadic cases, including c.639T/C, c.678T/C, c.1209G/T, c.1227T/C, c.1659G/A, and c.1629C/T. The SNP D190D was hererozygous and absent in 200 healthy controls.</p><p><b>CONCLUSION</b>This results suggested that mutations of the CHRNA4 gene may be rare in southern Chinese population with ADNFLE. The synonymous mutation D190D has not been reported previously. Its impact on the pathogenesis of ADNFLE warrant further study.</p>

Mutation analysis of CRYBB1 gene and prenatal diagnosis for a Chinese kindred featuring autosomal dominant congenital nuclear cataract / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To perform mutation screening and prenatal diagnosis for a five-generation Chinese pedigree with autosomal dominant congenital nuclear cataract from Henan province by DNA sequencing.</p><p><b>METHODS</b>Blood samples were taken from the family members. Four candidate genes (CRYBA1/A3, CRYBB1, CRYBB2 and CRYGD) were screened for mutations using direct sequencing. Prenatal genetic diagnosis was provided for a fetus at early gestation through chorionic villus sampling.</p><p><b>RESULTS</b>A missense mutation, c.387C to A, was detected in exon 4 of the CRYBB1 gene in all of the patients. The mutation has resulted in a p.S129R transversion. The same mutation was not found in the fetus of the proband, who was confirmed to be healthy by one-year follow-up.</p><p><b>CONCLUSION</b>A missense mutation p.S129R of the CRYBB1 gene probably underlies the autosomal dominant congenital nuclear cataract in this pedigree. Detection of the mutation also facilitated prenatal genetic testing for the family.</p>

Analysis of gene mutation in a family featuring autosomal dominant May-Hegglin anomaly / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze clinical features and mutation in MYH9 gene for a family featuring autosomal dominant May-Hegglin anomaly.</p><p><b>METHODS</b>Clinical and pathological features of all family members were analyzed. Blood samples were collected from the proband and other family members, and genomic DNA was extracted. Potential mutations of MYH9 gene exons 10, 25, 26, 30, 38 and 40 were screened with PCR and direct sequencing. After a mutation was identified in the proband, other affected members as well as healthy members from this family were analyzed with a pair of primers to amplify the mutant site. The PCR products were digested with Taq I enzyme and analyzed with agarose gel electrophoresis.</p><p><b>RESULTS</b>All affected members had bleeding tendency and typical features including giant platelets, thrombocytopenia and characteristic Dohle body-like leukocyte inclusions. A heterozygous missense mutation c.5521G>A (p.Glu1841Lys) in exon 38 of the MYH9 gene was identified in all affected members from this family.</p><p><b>CONCLUSION</b>The variant, c.5521G>A (p.Glu1841Lys) of MYH9, has co-segregated with the phenotype in the family. The mutant site is a hot spot in Chinese population.</p>

Clinical and genetic features of a large Chinese family with nonsyndromic autosomal dominant hearing loss / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the clinical and genetical characteristics of a Chinese family with an autosomal-dominant inherited high-frequency sensorineural hearing loss.@*METHOD@#Pedigree was drawn after investigation. Fifeteen family members were checked up, and detailed audiological examination was performed.@*RESULT@#The proband of the kindred had been diagnosed with senserineural hearing loss. A Chinese family SX-G087 with non-sysdromic hearing loss was ascertained. The inheritance pattern of this family is autosomal dominant based on the investigated information. The affected members showed postlingual, progressive, bilateral moderate to severe sensorineural hearing impairment. The age of onset varied from 20 to 35 years. The hearing loss began at high frequencies, and lower frequencies became involved with increasing age.@*CONCLUSION@#Pedigree analysis suggested an autosomal-dominant inheritance pattern in this family. The information should facilitate linkage analysis and positional cloning for the causative gene of this family.

A preliminary study on the genetic mode of aggressive periodontitis in Chinese Han nationality / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the potential genetic mode of aggressive periodontitis (AgP) in Chinese Han nationality.</p><p><b>METHODS</b>A total of 233 subjects from 73 nuclear families were recruited. All probands were diagnosed according to the criteria of AgP in 1999 classification of periodontal diseases. Ninety parents, 35 siblings and three grandparents and two offspring were examined based on full-mouth periodontal chartings (including parameter of probing depths, attachment loss, bleeding on probing at six sites per tooth) and full-mouth periapical radiographs. The genetic ratio was calculated and analyzed by the methods of Edwards and simple segregation.</p><p><b>RESULTS</b>The prevalence of AgP in probands' siblings was close to the square root of the prevalence of general population. The segregation ratio was 0.2419, which was close to the theoretical ratio for autosomal recessive inheritance. However, autosomal dominant inheritance could not be rejected in families whose parent(s) suffered from severe chronic periodontitis.</p><p><b>CONCLUSIONS</b>The genetic heterogeneity of AgP existed in Chinese Han nationality. The genetic mode was autosomal recessive inheritance in general, and autosomal dominant inheritance could not be excluded in families whose parent(s) suffered from severe chronical periodontitis. The results imply the genetic heterogeneity of AgP, and further demonstrate that AgP was a multifactorial disease with major genetic component in the disease etiology.</p>

Chronic ethanol consumption in mice does not induce DNA damage in somatic or germ cells, evaluated by the bone marrow micronucleous assay and the dominant lethal mutation assay

Although alcohol is known to be a carcinogen for humans, ethanol-genotoxicity studies are incomplete. Ethanol seems not to be a bacterial mutagen, but the results are conflicting in rodent assays. We investigate the genotoxicity in the bone marrow micronucleus (MN) test and in the dominant lethal mutation (DLM) assay using two long-term ethanol exposure protocols. In the MN test, mice consumed three doses (5, 10 and 15% v/v) for 32 weeks. MN induction was compared to two control groups of 5- and 38-week-old mice (the ages of the treated mice when the treatment was initiated and when they were killed, respectively). For the three groups treated with ethanol there was no significant increase in MN induction as compared to the first control group, but observed MN frequencies were significantly lower than in the 38-week-old control group. This suggests a protective effect against genotoxic damage caused by aging, probably due to ethanol action as a hydroxyl radical scavenger. In the DLM assay, male mice drank ethanol at 15% or 30% (v/v) for 20 weeks. In both groups the number of dead implants was similar to the control, but there was a significant reduction in total implants, indicating a pre-implantation loss.

Tuberous sclerosis presented with polycystic kidney disease and acute renal failure

Tuberous sclerosis complex [TSC] is an autosomal dominant disorder characterized by hamartomatous involvement of multiple organs such as the skin, central nervous system, kidneys, lungs, and heart. A linkage has been found with a locus on the long arm of chromosome 9 [9q34] and with a locus on the short arm of chromosome 16 [16p13]. TSC has a birth incidence of 1/6000. Children with TSC are almost universally born with normal kidneys, but cystic disease and angiomyolipomas develop with increasing age. Angiomyolipomas, renal cysts, and renal cell carcinoma are classical features of renal involvement in TSC. Renal complications are the most common cause of death in adult TSC patients, thus renal involvement has a crucial importance on the course of this disease. We present a 27-year-old patient previously diagnosed as tuberous sclerosis complex and referred with acute renal failure and polycystic kidney disease

Inhibition of HBV replication by VPS4B and its dominant negative mutant VPS4B-K180Q in vivo / 华中科技大学学报（医学）（英德文版）

This study examined the anti-hepatitis B virus (HBV) effect of wild-type (WT) vacuolar protein sorting 4B (VPS4B) and its dominant negative (DN) mutant VPS4B-K180Q in vivo in order to further explore the relationship between HBV and the host cellular factor VPS4. VPS4B gene was amplified from Huh7 cells by RT-PCR and cloned into the eukaryotic expression vector pXF3H. Then, the VPS4B plasmid and the VPS4B-K180Q mutation plasmid were constructed by using the overlap extension PCR site-directed mutagenesis technique. VPS4B and HBV vectors were co-delivered into mice by the hydrodynamic tail-vein injection to establish HBV vector-based models. Quantities of HBsAg and HBeAg in the mouse sera were determined by ElectroChemiLuminescence (ECL). HBV DNA in sera was measured by real-time quantitative PCR. Southern blot analysis was used to assay the intracellular HBV nuclear capsid-related DNA, real-time quantitative PCR to detect the HBV-related mRNA and immunohistochemical staining to observe the HBcAg expression in the mouse liver tissues. Our results showed that VPS4B and its mutant VPS4B-K180Q could decrease the levels of serum HBsAg, HBeAg and HBV-DNA. In addition, the HBV DNA replication and the mRNA level of HBV in the liver tissues of treated mice could be suppressed by VPS4B and VPS4B-K180Q. It was also found that VPS4B and VPS4B-K180Q had an ability to inhibit core antigen expression in the infected mouse liver. Furthermore, the anti-HBV effect of mutant VPS4B-K180Q was more potent than that of wild-type VPS4B. Taken together, it was concluded that VPS4B and its DN mutant VPS4B-K180Q have anti-HBV effect in vivo, which helps develop molecular therapeutic strategies for HBV infection.

Genetic power of a brazilian three-generation family with generalized aggressive periodontitis. II

The genetic power of a Brazilian three-generation family with generalized aggressive periodontitis (GAgP) has been reported. The empirical logarithms of the odds (LOD) score thresholds for genetic linkage analysis of complex diseases proposed by Haines rely on confirmation from independent datasets. This study estimated the power of another large Brazilian family with GAgP for future linkage analysis. The three-generation family was seen at the Dental School of the Federal University of Bahia. Following the previously described methodology, full-mouth periodontal probing at 6 sites/tooth was performed in all 19 family members. Six out of 12 siblings were affected with GAgP. All affected family members were non-smokers and did not present diabetes or any other systemic condition or consanguinity. A parametric simulation (?=0) was performed on 100 replicates using the statistical software SLINK for linkage analysis. There was maximum expected LOD scores of 3.75 and 3.45 at penetrance rate F=0.98, and both studied phenocopy rates P=0.0 and P=0.02, respectively. The power of the study increased with the increase of the adopted penetrance rates in both studied phenocopy rates. The studied Brazilian three-generation family showed statistical power for future genetic linkage analysis of candidate genes to GAgP.

O poder genético em uma família brasileira de três gerações com periodontite agressiva generalizada (PAgG) foi reportado. Os valores dos escores logarítmicos (LOD) empíricos para análise genética de ligação de doenças complexas propostos por Haines se baseam na confirmação em conjuntos de dados independentes. O objetivo deste estudo foi de estimar o poder de uma nova grande família com PAgG para futura análise de ligação. A família de três gerações foi vista na Faculdade de Odontologia da Universidade Federal da Bahia. De acordo com metodologia previamente descrita, sondagem periodontal em 6 sítios/dente foi realizada em todos 19 membros da família. Seis de 12 irmãos apresentaram PAgG. Todos os membros afetados da família eram não fumantes, não apresentaram diabetes ou qualquer condição sistêmica ou consangüinidade. Uma simulação paramétrica (?=0) foi realizada em 100 réplicas usando software estatístico SLINK para análise de ligação. Houve escore LOD esperado máximo de 3,75 e 3,45 no valor de penetrância F=0,98 em ambas razões de fenocópia estudadas P=0,0 e P=0,02, respectivamente. O poder do estudo aumento com o aumento do grau de penetrância adotado em ambas razões fenotípicas estudadas. A família brasileira de três gerações estudada mostrou poder estatístico para futura análise de ligação genética de genes candidatos para PAgG.