Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort.

PURPOSE: Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES). METHODS: After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes. RESULTS: We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%), and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects. CONCLUSION: We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371.

Anticoagulant proteins in a population of Mexican mestizo donors.

BACKGROUND: To determine the activity of antithrombin (AT), protein C (PC), and protein S (PS), as well as the frequency of deficiencies of these proteins in a population of healthy Mexican mestizo blood donors. METHODS: AT, PC, and PS were determined from 1,502 plasma samples of healthy blood donors by using commercial kits in a coagulometer 4 STA (Diagnostica Stago, Asnières, France). RESULTS: A total of 741 women and 761 men were under study. They were divided into age range groups (18-24, 25-34, 35-44, 45-54, and 55-64 years). Activity of AT, PC, and PS was determined. For AT, activity values were specific for each age group according to gender when it had to do with PS, as well as when PC was determined. Frequencies of AT, PC, PS, and activated PC resistance activity deficiencies were obtained from reference levels (RLs) and average levels of this study. Differences were found between both frequencies for AT, PC, and PS, and the average levels obtained were used in this study. The frequencies of the activity deficiencies obtained through the values gotten in this population were: AT, 0.6%; PC, 1.06% (which is higher than the one obtained using the RLs described by commercial kits 0.33% and 0.66%, respectively); and PS, 1% (which is less than 4.5%). CONCLUSIONS: It is necessary to know the characteristics and biological behavior of the coagulation proteins in the Mexican population because the RLs used have been established for populations that are genetically different.

Risk Factors for Thrombosis Development in Mexican Patients.

BACKGROUND: To identify inherited factors: Protein C (PC), protein S (PS), antithrombin (AT), plasminogen (Plg), the activated PC resistance (APCR), prothrombin (PT) mutation G20210 A (PTG20210 A) and methylenetetrahydrofolate reductase C677 T polymorphism (MTHFR C677 T), as well as acquired-risk factors such as: diabetes mellitus, surgeries, smoking, obesity, hypertension, trauma, alcoholism, family history; and their association, in Mexican patients with diagnostic of thrombophilia. METHODS: Overall, 200 patients diagnosed with thrombophilia and 100 healthy controls. Commercial kits were used for the coagulometric tests and polymerase chain reaction, restriction fragment length polymorphism for molecular alterations. RESULTS: Alterations were found with an estimated prevalence to PC 0.65%, AT 2.04% and Plg 2.5%, APCR 2%, PT 20210 2%, and MTHFR 65%. The C677 T polymorphism of the MTHFR did not associate with acquired-risk factors so we can suppose that it is an independent risk factor. For the patients that only presented acquired-risk factors (21 of 200), the association smoking-alcoholism showed to be the cause of thrombosis with high risk. The following were also associated: smoking with AT, PC, and alcoholism; obesity with Plg; smoking with alcoholism, and PS deficiency. CONCLUSIONS: Risk factors for both primary and secondary and their association were present as a cause of thrombosis in the patients studied, and the possibility to suffer a recurrent thrombosis.

[The auditory pathway: levels of integration of information and principal neurotransmitters]. / La vía auditiva: niveles de integración de la información y principales neurotransmisores.

In this paper we studied the central auditory pathway (CAP) from an anatomical, physiological and neurochemical standpoint, from the inner ear, brainstem, thalamus to the temporal auditory cortex. The characteristics of the spiral ganglion of Corti, auditory nerve, cochlear nuclei, superior olivary complex, lateral lemniscus, inferior colliculus, medial geniculate body, and auditory cortex, including the auditory efferent pathway, are given. CAP is described as the electrical impulses, travelling through axons, allowing ions to enter a neuron and vesicles with neurotransmitters (NT) and then released into synaptic space. The NT changes the functioning of the cells; when attached to specific receptors on the next nerve cell, NT-receiver union causes input of ions through Gap sites, resulting in a postsynaptic potential that is spread over all CAP. In addition, the effects of the NT are not limited to the transmission, but as trophic agents that promote the formation of new neural networks. Even the anatomy, physiology, neurochemical aspects, and the different types of synapses are not fully understood to comprehend the organization of the CAP, but remain under investigation because of the relevance for the treatment of various central auditory disorders.

New Genetic Variants of RUNX2 in Mexican Families Cause Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterized by persistent open skull sutures with bulging calvaria, hypoplasia, or aplasia of clavicles permitting abnormal opposition of the shoulders; wide public symphysis; short middle phalanx of the fifth fingers; and vertebral, craniofacial, and dental anomalies. It is a rare disease, with a prevalence of 1-9/1,000,000, high penetrance, and variable expression. The gene responsible for CCD is the Runt-related transcription factor 2 (RUNX2) gene. We characterize the clinical, genetic, and bioinformatic results of four CCD cases: two cases within Mexican families with six affected members, nine asymptomatic individuals, and two sporadic cases with CCD, with one hundred healthy controls. Genomic DNA analyses of the RUNX2 gene were performed for Sanger sequencing. Bioinformatics tools were used to predict the function, stability, and structural changes of the mutated RUNX2 proteins. Three novel heterozygous mutations (c.651_652delTA; c.538_539delinsCA; c.662T>A) and a previously reported mutation (c.674G>A) were detected. In silico analysis showed that all mutations had functional, stability-related, and structural alterations in the RUNX2 protein. Our results show novel mutations that enrich the pool of RUNX2 gene mutations with CCD. Moreover, the proband 1 presented clinical data not previously reported that could represent an expanded phenotype of severe expression.

Bone Remodeling and Bone Structural Genes in Legg-Calvé-Perthes Disease: The OPG rs2073618 and IL-6 rs1800795 Are Associated with High Risk in Mexican Patients.

Legg-Calve-Perthes disease (LCPD) is an idiopathic avascular necrosis of the pediatric femoral head. Bone remodeling and bone structural genes have the potential to contribute to the progression of LCPD when there is disequilibrium between bone resorption and bone formation. A case-control study was performed to search for associations of several common polymorphisms in the genes Receptor Activator for Nuclear Factor κappa B (RANK), Receptor Activator for Nuclear Factor κappa B Ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, and type 1 collagen (COL1A1) with LCPD susceptibility in Mexican children. A total of 23 children with LCPD and 46 healthy controls were genotyped for seven polymorphisms (rs3018362, rs12585014, rs2073618, rs1800795, rs1800796, rs1800012, and rs2586498) in the RANK, RANKL, OPG, IL-6, and COL1A1 genes by real-time polymerase chain reaction with TaqMan probes. The variant allele (C) of IL-6 rs1800795 was associated with increased risk of LCPD (odds ratio [OR]: 3.8, 95% confidence interval [CI]: [1.08-13.54], p = 0.033), adjusting data by body mass index (BMI) and coagulation factor V (FV), the association with increased risk remained (OR: 4.9, 95% CI: [1.14-21.04], p = 0.025). The OPG polymorphism rs2073618, specifically GC-GG carriers, was associated with a more than fourfold increased risk of developing LCPD (OR: 4.34, 95% CI: [1.04-18.12], p = 0.033) when data were adjusted by BMI-FV. There was no significant association between RANK rs3018362, RANKL rs12585014, IL-6 rs1800796, COL1A1 rs1800012, and rs2586498 polymorphisms and LCPD in a sample of Mexican children. The rs1800975 and rs2037618 polymorphisms in the IL-6 and OPG genes, respectively, are informative markers of increased risk of LCPD in Mexican children.

Prothrombin Time and Coagulation Factor IX as Hemostatic Risk Markers for Legg- Calvé-Perthes Disease.

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) is a pediatric disorder that occurs due to the avascular necrosis of the femoral head and affects the range of motion of the hip in various degrees. Its etiology is still unknown, although it has been associated with coagulation abnormalities, however, the lack of reproducibility in the results in various studies has created a controversy as to whether hemostasis disorders are related to LCPD. On the other hand, there is little information on laboratory studies that could facilitate the diagnosis and treatment of LCPD. METHODS: Blood and plasma samples were tested from 25 patients with LCPD and 50 healthy controls, matched by sex and age. Cellular markers were evaluated through complete blood count, as well as coagulation times, coagulation factors activity, antithrombotic proteins, and homocysteine concentration. RESULTS: After assessing activity value frequencies in each group, the results showed more significant activity in some of the biological risk markers of thrombophilia, presenting a substantial difference in prothrombin time↘, FV↗, FVIII↗, FIX↗, and Hcy↗. These values imply that there may be hypercoagulable states in patients, which can cause thrombotic events. CONCLUSIONS: Diminished prothrombin time and increase in FV activity, FVIII, FIX, and Hcy concentration support the hypothesis that microthrombi formation in small-caliber vessels could be causing avascularity and femoral necrosis, which are traits of LCPD. In addition, based on our results, we believe that the laboratory studies carried out are very useful in the diagnosis and treatment of LCPD.

Legg-Calvé-Perthes disease overview.

BACKGROUND: Legg-Calvé-Perthes Disease (LCPD) is a necrosis of the femoral head which affects the range of motion of the hips. Its incidence is variable, ranging from 0.4/100,000 to 29.0/ 100,000 children. Although LCPD was first described in the beginning of the past century, limited is known about its etiology. Our objective is to describe the main areas of interest in Legg-Calve-Perthes disease. METHODS: A review of the literature regarding LCPD etiology was performed, considering the following inclusion criteria: Studies reporting clinical or preclinical results. The research group carried out a filtered search on the PubMed and Science Direct databases. To maximize the suitability of the search results, we combined the terms ''Perthes disease" OR "LCPD" OR "children avascular femoral head necrosis" with "diagnostic" OR "treatment" OR "etiology" as either key words or MeSH terms. RESULTS: In this article been described some areas of interest in LCPD, we include topics such as: history, incidence, pathogenesis, diagnosis, treatment and possible etiology, since LCPD has an unknown etiology. CONCLUSIONS: This review suggests that LCPD has a multifactorial etiology where environmental, metabolic and genetic agents could be involved.

Association of MTHFR rs1801133 and homocysteine with Legg-Calvé-Perthes disease in Mexican patients.

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) is the avascular osteonecrosis of the proximal femoral epiphysis. It is a rare disease of unclear etiology in children, although alterations in coagulation or the collagen gene have been described and could be associated with its etiology. Our objective was to evaluate the following alterations: COL1A1 (rs1107946, rs2412298), COL2A1 (rs121912891 and rs387106558), MTHFR rs1801133, CBS rs115742905, and PT rs1799963 and their relationship with LCPD. METHODS: DNA was obtained and genotyped by real-time PCR with TaqMan probes. Prothrombin (FII) and homocysteine (Hcy) were determined by a coagulometric method. The variables were described as mean and standard deviation or percentages, and genotypic and allelic distributions were analyzed using the Student's t-test. The Hardy-Weinberg equilibrium and OR were also used. RESULTS: We studied 23 patients with LCPD and 46 controls. We did not find any association of the MTHFR, CBS, PT, COL1A1, and COL2A1 genetic variants with LCPD. However, when adjusting the data with the Hcy values for the MTHFR C677T polymorphism, the C/C genotypes showed an association with the recessive model (p = 0.038), with susceptibility to LCPD. CONCLUSION: No association was found with the CBS, PT, COL1A1, and COL2A1 genes. Nevertheless, our results suggest a significant link between moderately elevated Hcy levels and the MTHFR C677T polymorphism in a cohort of Mexican children with LCPD.

Association of Polymorphisms in Estrogen Receptor Genes (ESR1 and ESR2) with Osteoporosis and Fracture-Involvement of Comorbidities and Epistasis.

Single-nucleotide polymorphisms (SNPs) in the ESR1/ESR2 genes play a role in osteoporosis (OP). Our objective was to determine associations of polymorphisms in ESR genes with OP and fracture, SNP-SNP interactions, and involvement of comorbidities. We analyzed 170 Mexican osteoporotic women (FNOP), 173 with hip fracture (HFx), and 210 controls. The SNPs, ESR1 rs2234693CC, rs851982CC and rs1999805AA, were associated with reduced OP risk (odds ratios [ORs] = 0.35, 0.40 and 0.32, respectively; p < 0.05); rs2234693CC was associated with reduced fracture risk (OR = 0.24; p < 0.05). The obese/overweight carriers of rs9340799GG had a lower OP (OR = 0.15, p = 0.016) and fracture (OR = 0.12, p = 0.0057) risk. The rs9479055AA and rs3020404AA hypertensive carriers had a higher OP risk (OR = 5.96, p = 0.032; and OR = 5.29, p = 0.02, respectively). In addition, rs3020404AA had a higher risk of fracture (OR = 4.90, p = 0.045). The rs2228480GG hypertensive carriers had a higher risk of fracture (OR = 6.22, p = 0.0038). We found a synergic relation between the ESR1 rs3020331 and rs1999805 in femoral neck OP and HFx. The rs2234693 (PvuII) and rs9340799 (XbaI) polymorphisms are associated with a high risk forming a haplotype. The epistasis analysis suggests the contribution of both genes (ESR1/ESR2) to the risk of OP and fracture. Epistasis and involvement of obesity and hypertension lead to a significant modification of the risk.

[Microarray design using virtual hybridization to study variations in REP-CMT1A sites]. / Diseño de microsondas mediante hibridación virtual para el estudio de variantes en los sitios REP-CMT1A.

BACKGROUND: Gene PMP22 is duplicated in patients with CMT1A. Duplication is due to an unequal chromatid interchange during meiosis that takes place between two 24 Kb regions named REP-CMT1A proximal and distal sites. Homology is approximately 98%. Within each one of the sites we find zones termed hot spots where a greater number of variants and mutations could give origin to an unequal interchange. The aim of this study was to design a set of probes to create a microarray that could detect the presence of variants and mutation points in distal and proximal REP sites among patients with CMT1A. MATERIAL AND METHODS: With reported sequences of distal and proximal REPs, we determined hot spot sites within proximal and distal regions. These sequences were aligned and matched, hence 12 zones were detected. RESULTS AND CONCLUSIONS: Twenty four probes were designed and analyzed using the Genosensor Probe Designer program. Probes could be synthesized and used in a microarray that is able to find variations and mutation points and facilitates diagnosis of patients with CMT1A.

Microbial biofilms and their impact on medical areas: physiopathology, diagnosis and treatment. / Biopelículas microbianas y su impacto en áreas médicas: fisiopatología, diagnóstico y tratamiento

Biofilms are communities of microorganisms that grow aggregated and surrounded by an extracellular matrix, which they produce and favors them to adhere covalently to inert and living surfaces; it also helps them to develop high tolerance to molecules with antimicrobial activity. Moreover, biofilms are associated with chronic and persistent infections, which negatively impact different medical areas since they generate high costs to health care systems and patients every year because they are difficult to treat with conventional antimicrobial drugs. Additionally, they generate high rates of morbidity and mortality. The objective of this review was to present extensive and up-to-date information on the origin, biosynthesis, and pathophysiology of biofilms. Also, its relationship with chronic infections, diagnosis, current antimicrobial treatments with antibiotic activity, and perspectives on the search for new treatments, since the latter still represent an important area of research.

Las biopelículas son comunidades de microorganismos que crecen agregados y rodeados por una matriz extracelular que ellos mismos producen, la cual favorece la adhesión covalente sobre superficies inertes y vivas; además, les ayuda a desarrollar alta tolerancia a las moléculas con actividad antimicrobiana. Por otra parte, las biopelículas se asocian con infecciones crónicas y persistentes que impactan de manera negativa en distintas áreas médicas. Además, generan altos costos a los sistemas de salud y a los pacientes cada año, porque son difíciles de tratar con antimicrobianos convencionales; adicionalmente, generan altas tasas de morbilidad y mortalidad. El objetivo de esta revisión es presentar información extensa y actualizada sobre el origen, la biosíntesis y la fisiopatología de las biopelículas, así como sobre su relación con infecciones crónicas, el diagnóstico, los tratamientos antimicrobianos actuales con actividad antibiopelícula y las perspectivas sobre la búsqueda de nuevos tratamientos. Estos últimos aún representan una importante área de investigación.

Oral pathology in a group of Mexican patients with genetic diseases.

UNLABELLED: Without considering infectious and traumatic diseases, the great majority of oral cavity diseases have a genetic base, in some cases identifiable, in others not. For the stomatologists it is of great importance to know the clinical characteristics and type of alteration that go with genetic etiology syndromes to be able to offer patients an adequate multidisciplinary treatment. OBJECTIVE: Intentional search and description of oral pathology in patients with diverse genetic diseases. STUDY DESIGN: An observational and descriptive 4 month study of 62 patients from the Genetics Department of the National Institute of Rehabilitation, was done. Taken into consideration, aside from oral manifestations and genetic disease, were age, sex, consanguinity and inbreeding. The majority of patients who have genetic pathology do not have curative treatment, but they can receive other treatments to improve their quality of life, among these are dental treatments. RESULTS: The more common diseases we found were hereditary peripheral neuropathies, skeletal dysplasias, limb malformation and muscular dystrophies. Diverse features were described, registered and grouped according to their location. CONCLUSIONS: Presently it is important to look for the genetic etiology of all diseases to seek specific treatments and prevent them. This will change the practice of medicine and dentistry.

[Gene doping: gene transfer and possible molecular detection]. / Dopaje genético: transferencia génica y su posible detección molecular.

The use of illegal substances in sports to enhance athletic performance during competition has caused international sports organizations such as the COI and WADA to take anti doping measures. A new doping method know as gene doping is defined as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". However, gene doping in sports is not easily identified and can cause serious consequences. Molecular biology techniques are needed in order to distinguish the difference between a "normal" and an "altered" genome. Further, we need to develop new analytic methods and biological molecular techniques in anti-doping laboratories, and design programs that avoid the non therapeutic use of genes.

[Strategies for clinical and molecular diagnosis of Charcot-Marie-Tooth 1A among Mexican patients]. / Estrategias para el diagnóstico clinico y molecular de Charcot-Marie-Tooth 1A. Estudio en pacientes mexicanos.

BACKGROUND: Charcot-Marie-Tooth (CMT) is the most common inherited disorder of the human peripheral nerve. The mos tfrequent subtype, CMT1A, is associated with duplication of approximately 1.5 Mb fragment in 17p11-p12, that includes the PMP22 gene. OBJECTIVE: The aim of this study was to describe different strategies used for clinical and molecular CNT1A diagnoses among patients attending the National Rehabilitation Institute of Mexico (INR). MATERIAL AND METHODS: 17 patients had clinical and electrophysiological features compatible with CMT1. A molecular study using capillary electrophoresis (CE) was performed and a PMP22 gene duplication was detected RESULTS: Clinical, biochemical and electrophysiological studies constituted the inclusion criteria to establish a CMT1 diagnosis. With CE the duplication of the PMP22 gene was observable and we established a possible CMT1A diagnosis in seven patients. All duplications detected by capillary electrophoresis were corroborated using FISH. CONCLUSION: CE is a feasible and reliable method to detect PMP22 gene duplication. Using different clinical, electrophysiological and molecular strategies in this patient population allowed us to establish an accurate diagnosis and offer suitable genetic counseling.

Novel pathogenic variants underlie SLC26A4-related hearing loss in a multiethnic cohort.

OBJECTIVES: The genetics of sensorineural hearing loss is characterized by a high degree of heterogeneity. Despite this heterogeneity, DNA variants found within SLC26A4 have been reported to be the second most common contributor after those of GJB2 in many populations. METHODS: Whole exome sequencing and/or Sanger sequencing of SLC26A4 in 117 individuals with sensorineural hearing loss with or without inner ear anomalies but not with goiter from Turkey, Iran, and Mexico were performed. RESULTS: We identified 27 unique SLC26A4 variants in 31 probands. The variants c.1673A > G (p.N558S), c.1708-1G > A, c.1952C > T (p.P651L), and c.2090-1G > A have not been previously reported. The p.N558S variant was detected in two unrelated Mexican families. CONCLUSION: A range of SLC26A4 variants without a common recurrent mutation underlies SLC26A4-related hearing loss in Turkey, Iran, and Mexico.

Cockayne's syndrome: a case report. Literature review.

Cockayne s syndrome is a genetic disorder with a recessive autosomal inheritance, described first by Cockayne in 1936. Patients with this syndrome present failure to thrive, short stature, premature aging, neurological alterations, photosensitivity, delayed eruption of the primary teeth, congenitally absent of some permanent teeth, partial macrodontia, atrophy of the alveolar process and caries. It could be caused by two gene mutations, CNK1 (ERCC8) and ERCC6, located on the 5 and 10 chromosomes respectively, causing two variations of Cockayne s syndrome, CS-A, secondary to a ERCC8 mutation and CS-B with ERCC6 mutation, the last one causes hypersensitivity to the ultraviolet light secondary to a DNA repair defect. The syndrome is also associated with mutations of the XPB, XPD and XPG genes. In this report we present a 9 year and 4 month old patient. He had a height of 94 cm, weight of 8.6 Kg, head circumference of 42 cm. and blood pressure of 120/80. Cachectic habitus, kyphosis, microcephaly, oval face, sunken eyes, a thin and beaklike nose, lack of subcutaneous facial fat (especially in the middle of the face), and large ears give the patient a birdlike appearance. It is notorious the photosensitivity in all the sun-exposed skin. The patient also displays delayed psychomotor skills and mental retardation. In the oral cavity we found deficient hygiene, gingivitis, cervical caries, enamel hipoplasia, abnormal position of the upper and inferior lateral incisors, macrodontia of the upper central teeth, the left one presented a caries. In the x-ray we observed congenital absence of 14, 23 and 24 teeth and mandibular hipoplasia. The aim of this review is to show the dentistry community the characteristics of the Cockayne s syndrome by means of a clinical case.

Characterization of a group unrelated patients with arthrogryposis multiplex congenita.

OBJECTIVE: Arthrogryposis multiplex congenita is a relatively rare neuromuscular syndrome, with a prevalence of 1:3000-5000 newborns. In this study, the authors describe the clinical features of a group of 50 unrelated Mexican patients with arthrogryposis multiplex congenita. METHODS: Patients were diagnosed by physical and radiographic examination and the family history was evaluated. RESULTS: Of the 50 cases, nine presented other features (pectum excavatum, cleft palate, mental retardation, ulnar agenesis, etc.). Environmental factors, as well as prenatal and family history, were analyzed. The chromosomal anomalies and clinical entities associated with arthrogryposis multiplex congenita were reported. No chromosomal aberrations were present in the cases with mental retardation. Three unrelated familial cases with arthrogryposis multiplex congenita were observed in which autosomal recessive, autosomal dominant and X-linked inheritance patterns are possible. A literature review regarding arthrogryposis multiplex congenita was also conducted. CONCLUSIONS: It is important to establish patient-specific physical therapy and rehabilitation programs. A multidisciplinary approach is necessary, with medical, surgical, rehabilitation, social and psychological care, including genetic counseling.

Incontinentia pigmenti (IP2): familiar case report with affected men. Literature review.

UNLABELLED: Incontinentia pigmenti is a genodermatosis described by Garrod and in 1920 by Bloch, Sulzberger, Siemens y Bardach. It is an ectodermic disorder that affects skin, teeth, eyes and may also have neurological problems. The IP2 name describes the histological characteristics, the incontinence of melanin into the melanocytes cells in the epidermal basal layer and its presence in superficial dermis. IP2 is an x-linked dominant condition but genetic heterogeneity may exist. CASE REPORT: The patient was 4 yrs 5 months old when she came for the first time. In a physical exploration she presented sparse and thin hair, eyelashes and eyebrows, beaked nose, labial protrusion, the four central teeth have a conic crown and there was also a delayed eruption of other teeth, right eye strabismus, hipoacusia, language defects and a trunk, legs, feet, and face dermatosis characterized by grouped vesicles, hyperkeratotic and warty lesions and brownish-gray lesions in a lineal pattern. The patient s father had hypopigmented lesions in the posterior regions of both legs. The oral clinical and radiographic exams showed diverse anomalies. Both the patient's and the father's chromosomal studies were normal. DISCUSSION: In the present case we can see that the father has IP2 without supernumeraries X, with the antecedent that his mother had something similar. It is possible that the inheritance was autosomic dominant or it is a different mutation of NEMO (NF-kappa-B essential modulator) gene to a classical one, which was found in some affected men. It is necessary to carry out a molecular study of these patients.