Síndrome PAGOD y anomalías vasculares: ¿es un defecto de la angiogénesis embrionaria? Un nuevo caso y revisión / PAGOD syndrome and vascular anomalies: is a defect embryonic angiogenesis? A case report and review

El Síndrome PAGOD es un acrónimo de hipoplasia de pulmón y arterias pulmonares, agonadismo, onfalocele / defecto diafragmático y dextrocardia. Se describe una serie de 21 pacientes, en la cual, 90,5 % presentó un cariotipo 46,XY y solo dos casos 46,XX; el 66,6 % exhibió un fenotipo femenino y 28,6 % genitales ambiguos. La ocurrencia de dos paciente 46,XX excluye al cromosoma Y como portador del defecto genético y plantea la posibilidad de una herencia recesiva ligada al cromosoma X, sin descartar que los casos observados en hermanos puedan deberse a mutaciones en otros genes como STRA6, VEGFA, VEGFB, VEGFC, transcritos de empalmes alternativos de VEGFA, HIF1, HIF2, entre otros. Las malformaciones congénitas observadas en los pacientes fueron: genitales y gónadas 85,7 %, diafragma y pared 66,6 %, cardíaco 80,9 %, pulmonar 71,4 %, vascular 80,9 % y abdomen 42,8 %. La revisión de los pacientes ha demostrado un alto grado de variabilidad en la expresividad de malformaciones de órganos, aparatos o sistemas. Las malformaciones vasculares representan un componente importante y característico del síndrome PAGOD y cuya base morfogenética del síndrome pueda deberse a un defecto de la angiogénesis embrionaria temprana con repercusión en la organogénesis de aparatos y sistemas. Dentro de los genes relacionados con el remodelamiento vascular durante la embriogénesis, regeneración tisular y carcinogénesis está el Factor de Crecimiento del Endotelio Vascular D (VEGFD), localizado en Xp22.31, con expresión en pulmón, corazón, intestino delgado, pulmón fetal, útero, mamas, tejido neural y neuroblastoma, el cual representa un fuerte candidato para su análisis molecular como una de las posibles causa del síndrome.

PAGOD Syndrome is an acronym for lung and pulmonary arteries hypoplasia, agonadism, omphalocele / diaphragmatic defect and dextrocardia. A series of 21 patients is described, where 90.5% had a 46,XY karyotype and only two cases 46,XX; 66.6% exhibited a female phenotype and 28.6% ambiguous genitalia. The occurrence of two patients 46,XX excludes the Y chromosome as a carrier of the genetic defect and raises the possibility of a recessive X-linked inheritance, without ruling out that the observed cases in siblings may be due to mutations in other genes as Stra6, VEGFA, VEGFB, VEGFC, and alternative splicing of transcripts VEGFA, HIF1, HIF2, among others. Congenital malformations were observed in patients’ genitals and gonads 85.7%, 66.6% in diaphragm and abdominal wall , heart 80.9%, 71.4% lungs, blood vessels 80.9% and 42.8% in abdomen. The review of patients has demonstrated a high degree of variability in the expression of malformations of organs and organ systems. Vascular malformations represent an important and characteristic component of PAGOD syndrome and whose base morphogenetic syndrome may be due to a defect in early embryonic angiogenesis with impact on organogenesis and system development. Among genes related to vascular remodeling during embryogenesis, tissue regeneration and carcinogenesis, the Endothelial Growth Factor D Vascular (VEGFD), located in the Xp22.31 region, with expression in lung, heart, small intestine, uterus, breast, neuroblastoma and neural tissue, represents a strong candidate for molecular analysis as a cause of the syndrome.

PAGOD syndrome and vascular anomalies: is a defect embryonic angiogenesis? A case report and review.

PAGOD Syndrome is an acronym for lung and pulmonary arteries hypoplasia, agonadism, omphalocele / diaphragmatic defect and dextrocardia. A series of 21 patients is described, where 90.5% had a 46,XY karyotype and only two cases 46,XX; 66.6% exhibited a female phenotype and 28.6% ambiguous genitalia. The occurrence of two patients 46,XX excludes the Y chromosome as a carrier of the genetic defect and raises the possibility of a recessive X-linked inheritance, without ruling out that the observed cases in siblings may be due to mutations in other genes as Stra6, VEGFA, VEGFB, VEGFC, and alternative splicing of transcripts VEGFA, HIF1, HIF2, among others. Congenital malformations were observed in patients' genitals and gonads 85.7%, 66.6% in diaphragm and abdominal wall , heart 80.9%, 71.4% lungs, blood vessels 80.9% and 42.8% in abdomen. The review of patients has demonstrated a high degree of variability in the expression of malformations of organs and organ systems. Vascular malformations represent an important and characteristic component of PAGOD syndrome and whose base morphogenetic syndrome may be due to a defect in early embryonic angiogenesis with impact on organogenesis and system development. Among genes related to vascular remodeling during embryogenesis, tissue regeneration and carcinogenesis, the Endothelial Growth Factor D Vascular (VEGFD), located in the Xp22.31 region, with expression in lung, heart, small intestine, uterus, breast, neuroblastoma and neural tissue, represents a strong candidate for molecular analysis as a cause of the syndrome.

Alelo doble mutante en el gen EXT1 no informado previamente en una adolescente con exostosis múltiple hereditaria / Double mutant alleles in the EXT1 gene not previously reported in a teenager with hereditary multiple exostoses

Las formas hereditarias de exostosis múltiple, actualmente denominada EXT1 / EXT2-CDG dentro de los desórdenes congénitos de la glicosilación, son los tumores óseos benignos más comunes y se caracterizan por la formación de lesiones óseas cubiertas de cartílago, localizadas en yuxtaposición a epífisis de huesos largos, aunque, en los casos graves, pueden presentar una amplia distribución. El inicio es variable desde los 2-3 años hasta los 13-15 y presenta una incidencia estimada que va de 1/18 000 a 1/50 000 casos en los países europeos. Se presenta el caso de un doble alelo mutante en el gen EXT1 no informado previamente en una adolescente y su familia con exostosis múltiple hereditaria.

Hereditary forms of multiple exostoses, now called EXT1/EXT2-CDG within Congenital Disorders of Glycosylation, are the most common benign bone tumors in humans and clinical description consists of the formation of several cartilage-capped bone tumors, usually benign and localized in the juxta-epiphyseal region of long bones, although wide body dissemination in severe cases is not uncommon. Onset of the Alelo doble mutante en el gen EXT1 no informado previamente en una adolescente con exostosis múltiple hereditariaDouble mutant alleles in the EXT1 gene not previously reported in a teenager with hereditary multiple exostosesdisease is variable ranging from 2-3 years up to 13-15 years with an estimated incidence ranging from 1/18 000 to 1/50 000 cases in European countries. We present a double mutant alleles in the EXT1 gene not previously reported in a teenager and her family with hereditary multiple exostoses

Alelo doble mutante en el gen EXT1 no informado previamente en una adolescente con exostosis múltiple hereditaria / Double mutant alleles in the EXT1 gene not previously reported in a teenager with hereditary multiple exostoses

Las formas hereditarias de exostosis múltiple, actualmente denominada EXT1 / EXT2-CDG dentro de los desórdenes congénitos de la glicosilación, son los tumores óseos benignos más comunes y se caracterizan por la formación de lesiones óseas cubiertas de cartílago, localizadas en yuxtaposición a epífisis de huesos largos, aunque, en los casos graves, pueden presentar una amplia distribución. El inicio es variable desde los 2-3 años hasta los 13-15 y presenta una incidencia estimada que va de 1/18 000 a 1/50 000 casos en los países europeos. Se presenta el caso de un doble alelo mutante en el gen EXT1 no informado previamente en una adolescente y su familia con exostosis múltiple hereditaria.(AU)

[Double mutant alleles in the EXT1 gene not previously reported in a teenager with hereditary multiple exostoses]. / Alelo doble mutante en el gen EXT1 no informado previamente en una adolescente con exostosis múltiple hereditaria.

Hereditary forms of multiple exostoses, now called EXT1/EXT2-CDG within Congenital Disorders of Glycosylation, are the most common benign bone tumors in humans and clinical description consists of the formation of several cartilage-capped bone tumors, usually benign and localized in the juxta-epiphyseal region of long bones, although wide body dissemination in severe cases is not uncommon. Onset of the disease is variable ranging from 2-3 years up to 13-15 years with an estimated incidence ranging from 1/18,000 to 1/50,000 cases in European countries. We present a double mutant alleles in the EXT1 gene not previously reported in a teenager and her family with hereditary multiple exostoses.

Mutation c.1190-1delG/N in intron 8 and c.1708G>C/N in exon 12 not reported in the IDUA gene developed a clinical phenotype of Scheie syndrome / Mutación c.1190-1delG/N en el intrón 8 y c.1708G>C/N en el exón 12 no reportada en el gen de IDUA desarrolló un fenotipo clínico de síndrome de Scheie

Mucopolysaccharidoses are a group of lysosomal storage disorders caused by deficiency of enzymes catalyzing the degradation of glycosaminoglycans. Mucopoly-saccharidosis I can present a wide range of phenotypic characteristics with three major recognized clinical entities: Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression. These are caused by the deficiency or absence of α-L-iduronidase, essential to the metabolism of both dermatan and heparan sulfate, and it is encoded by the IDUA gene. We report the case of a 34-year-old male patient with enzymatic deficiency of α-L-iduronidase, accumulation of its substrate and a previously unreported mutation in the IDUA gene that developed a phenotype of Scheie syndrome.

Las mucopolisacaridosis son un grupo de trastornos de almacenamiento lisosomal causada por la deficiencia de enzimas que catalizan la degradación de glicosaminoglicanos. La mucopolisacaridosis tipo I puede presentar un amplio rango de características fenotípicas englobadas en tres entidades clínicas reconocidas: los síndromes de Hurler y Scheie representan los fenotipos graves y leves del espectro clínico, respectivamente y el síndrome de Hurler-Scheie intermedio en la expresión fenotípica. Estos son causados por la deficiencia o ausencia de la α-L-iduronidasa esencial para el metabolismo del dermatán y el heparán sulfato y es codificada por el gen IDUA. Se presenta el caso de paciente masculino de 34 años de edad con deficiencia enzimática de α-L-iduronidasa, acumulación de su sustrato y una mutación en el gen IDUA, no reportada previamente, que desarrolló un fenotipo del síndrome de Scheie.

Mutation c.1190-1delG/N in intron 8 and c.1708G>C/N in exon 12 not reported in the IDUA gene developed a clinical phenotype of Scheie syndrome.

Mucopolysaccharidoses are a group of lysosomal storage disorders caused by deficiency of enzymes catalyzing the degradation of glycosaminoglycans. Mucopoly-saccharidosis I can present a wide range of phenotypic characteristics with three major recognized clinical entities: Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression. These are caused by the deficiency or absence of alpha-L-iduronidase, essential to the metabolism of both dermatan and heparan sulfate, and it is encoded by the lDUA gene. We report the case of a 34-year-old male patient with enzymatic deficiency of alpha-L-iduronidase, accumulation of its substrate and a previously unreported mutation in the IDUA gene that developed a phenotype of Scheie syndrome.

Petty-Laxova-Wiedemann progeroid syndrome: further phenotypical delineation and confirmation of a rare syndrome of premature aging.

A 10-year-old boy with manifestations of Petty-Laxova-Wiedemann progeroid syndrome (PLWPS), a rare neonatal progeroid condition, is described and compared with those previously reported. Clinical manifestation include: severe pre- and postnatal growth retardation, "progeroid" face, large open fontanelle in infancy, umbilical hernia at birth, pseudomacrocephaly, wide calvaria, sparse scalp hair, markedly diminished subcutaneous fat, scoliosis, partial cutaneous syndactyly, aplastic and hypoplastic distal phalanges with aplasia and hypoplasia of nails, undescended testes, and normal cognitive and motor development. This appears to be one of only a handful of cases of PLWPS reported in an older child or adult.

Autismo, cromosoma 15 y la hipótesis de disfunsión GABAérgica: revisión / Autism, chromosome 15 and the GABAergic dysfunction hypothesis: review

El autismo es un trastorno generalizado del desarrollo caracterizado por deterioro en las áreas de interacción social, comunicación, y comportamiento estereotipado y repetitivo. Estudios de familias y gemelos han demostrado una predisposición genética al autismo. A pesar de los avances recientes en la identificación de genes candidatos de susceptibilidad, la base neurológica subyacente es aún desconocida. Existe evidencia genética, bioquímica y anatomopatológica que apoyan la hipótesis de que en el autismo debe existir una disfunción en la vía GABAérgica, parcialmente responsable de la etiología de este trastorno. En este sentido, una de las regiones del genoma más estudiadas es el intervalo 15q11-q13, donde se encuentran los genes que codifican para las subunidades ß3, a5 y g3 del receptor GABAa. Esta revisión se propone mostrar la evidencia existente en la actualidad que involucra a esta región con la susceptibilidad al autismo y su posible relación con la hipótesis de disfunción GABAérgica.

[Molecular analysis of the GABRB3 gene in autistic patients: an exploratory study]. / Análisis molecular del gen GABRB3 en pacientes con autismo: estudio exploratorio.

Autism is a complex neurodevelopmental disorder characterized by impairment of social interaction, language, communication, and stereotyped, repetitive behavior. Genetic predisposition to Autism has been demonstrated in families and twin studies. There is evidence (linkage and genetic association, biochemical, neuropathological, functional and cytogenetic) that the gamma-amino-butyric acid receptor beta 3 subunit gene (GABRB3) at 15q11-q13 is a susceptibility candidate gene for Autism. The aim of this exploratory study was to identify new variants of this gene. We performed the molecular analysis (SSCP/Sequencing) of 10 exons and its intronic flanking regions of GABRB3, using a candidate gene screening approach in 18 idiopathic autistic patients. We did not find non-synonymous mutations at the encoding regions, but we identified four SNP (Single Nucleotide Polymorphism). The first one, represented a silent mutation p.P25P in exon la and was found in 33.33% of the patients. The second one: IVS3 + 13C > T (5b far from the intron 5' consensus sequence), was found in 44.44% of the patients, while it was also identified in 16.67% of the controls. Simultaneously, 33.33% of the patients had both variants, and although, 16.67% of the controls also had the same combination of variants, 66.66% of the patients with those alleles had a familiar history of Autism. The third and fourth SNP: IVS5 + 40T > G and IVS-70A > G were identified in two different patients. None of the last three SNPs have been reported at the SNP database (dbSNP). The proximity of SNP: IVS3 + 13C > T with the consensus and interaction sequence with U1 nucleoriboprotein, could disturb the normal splicing of mRNA. This is in agreement with the evidence of lower levels of GABA-A receptors in autistic brains; so, it could be a common variant, that by itself could not cause a phenotypic effect, but joined to other variants with the same gene, in different related genes or with epigenetic changes, could explain the autistic phenotype and its heterogeneity.

Análisis molecular del gen GABRB3 en pacientes con autismo: estudio exploratorio / Molecular analysis of the GABRB3 gene in autistic patients: an exploratory study

El autismoes un trantorno del desarrollo caracterizado por deterioro de la interacción social, la comunicación, y comportamiento estereotipado. Los estudios de familias y gemelos han demostrado predisposición genética al autismo. Existe evidencia (ligamento y asociación genética, bioquímica, anatomopatológica, funcional y citogenética) de que el gen de la subunidad B3 del receptor de GABA-A (GABRB3), en 15q11-q13, es un candidato de susceptibilidad al autismo. Con el objetivo de identificar nuevas variantes en este gen, se estudiaron 18 pacientes con autismo idiopático, utilizando un tamizaje de gen candidato. Se réalizo el análisis molecular (SSCP/secuencuaci¢n) de los 10 exones con sus correspondientes regiones intrónicas flanqueantes, pero se identificaron mutaciones no sinónimas en las regiones codificantes, pero se identificaron 4 polimorfismos de nucleótido simple (SNP). El primer SNP representó una mutación silente p. P25P en el exon 1a, encontrada en 33,33 por ciento de los pacientes. El Segundo SNP: IVS3 + 13C > T (a 5 b de la secuencia consenso 5' del intrón) fue encontrado en 44,44 por ciento de los pacientes, mientras fué indentificado en 16,67 por ciento de los controles. El 33,33 por ciento de los pacientes presentaron simultáneamente ambas variantes, y aunque el 16,67 por ciento de los controles también poseían la misma combinación, el 66,66 por ciento de los pacientes con esos alelos tenían antecedentes familiares de autismo. El tercer y cuarto SNP: IVS5 + 40T > G e IVS7-7OA > G fueron identificados en dos pacientes diferentes. Ninguno de los 3 últimos SNPs ha sido reportado en la base de datos de SNP (dbSNO). La cercanía del SNP: IVS3 + 13C > T con la secuencia consenso y de interación con la nucleorribonucleoproteína U1, pudiera alterar la maduración normal del pre-ARNm, en concordancia con la evidencia de niveles bajos del receptor GABA-A en cerebros de pacientes con autismo, pudiendo entonces tratarse, de una variante común, que por sí sola.

[Autism, chromosome 15 and the GAbaergic dysfunction hypothesis]. / Autismo, cromosoma 15 y la hipótesis de disfunción GABAérgica. Revisión.

Autism is a complex neurodevelopmental disorder characterized by impairment of social interaction, language, communication, and stereotyped, repetitive behavior. Genetic predisposition to autism has been demonstrated from families and twin studies. Despite recent advances in identifying some susceptibility candidate genes, its underlying neurological mechanism is uncertain. There are genetic, biochemical and neuropathological findings that support the hypothesis that autism could be caused by GABAergic dysfunction and it is partially responsible for the etiology of this disorder. One of the most studied genome regions is the 15q11-q13, where the genes that encode for beta3, alpha5 and gamma3 subunits of the GABAA receptor are located. This review demonstrates evidence that involves this region in autism susceptibility and its likely relation with the hypothesis of GABAergic dysfunction.

Medical genetics in Zulia, a State of Venezuela.

Zulia is a state located in the northwest of Venezuela. Congenital malformations, deformities and chromosomal anomalies are the second cause of infant and neonatal mortality. There are seven public and private groups providing genetic services, the most important of which, the Medical Genetic Unit at the Zulia University was created in 1973. So far, this unit has provided genetic services to 12,000 families, and has been responsible for undergraduate and postgraduate education in human and medical genetics. Prenatal diagnosis is performed at the Unit and a private practice group, the most frequent referral reason being advanced maternal age. The most frequent genetic diseases in the state are Huntington's disease, sickle cell anemia, neural tube defects and Down's syndrome. Research in genetics includes the clinical, epidemiological and molecular characterization of hereditary diseases, cancer, reproductive problems and genetic diversity. Other public groups are conducting research on dementias, including Alzheimer's disease, and on the genotoxic effects of environmental pollutants.

Human disorganization complex, as a polytopic blastogenesis defect: a new case.

We describe a baby girl of 4,000 g and 55 cm with supernumerary, malformed, and partially duplicated lower limbs, malformed and partially duplicated pelvis, spina bifida, coccygeal dermal sinus, ectopic anus located in the right buttock, duplicated internal genitalia, rectovaginal fistula, ileal atresia, Meckel diverticulum, and various renal system anomalies. We think that this phenotype is a new case of disorganization in humans (DsH) and postulate that this condition constitutes a polytopic defect of the blastogenesis. In this case, the presence of a malformation pattern involving structures in different parts of the body and organs derived from all of the germ layers, suggests that the pathogenetic event most probably occurred during blastogenesis affecting various progenitors fields.

Detección de portadoras de distrofia muscular Duchenne/Becker a través del análisis de loci STRs ligados al gen de la distrofina en familias venezolanas / Carrier Detection of muscular dystrophy Duchenne/Becker by analysis de STRs loci linked to the gene of the distrofina in venezuelan families

La Distrofia Muscular tipo Duchenne/Becker (DMD/DMB) es una enfermedad letal recesiva ligada al cromosoma X; el riesgo de recurrencia en una mujer portadora de DMD/DMB es de 50 por ciento de hijos sanos y 50 por ciento de hijos enfermos, 50 por ciento de hijas no portadoras y 50 por ciento de hijas portadoras, en cada gestación. El diagnóstico de DMD/DMB en una familia establece la necesidad de detectar a las mujeres portadoras con la finalidad de poder establecer el asesoramiento genético y el diagnóstico prenatal. El análisis de los polimorfismos de repeticiones cortas en tandem (STRs) localizados en los extremos 5, 3ïe intrones 44, 45, 49 y 50 del gen de la Distrofina se han utilizado para determinar los haplotipos en personas normales y en riesgo, a través de establecer el ligamiento genético entre el gen mutado y el haplotipo segregado. Se analizaron 105 individuos provenientes de 15 familias venezolanas con DMD/DMB, con uno o más afectados y 7 varones no emparentados. De los 105 individuos, 37 eran varones (26 afectados y 11 sanos) y 68 mujeres. Se amplificaron las secuencias STRs (STR44, STR45, STR49, STR 50 y STR3ïDYS) del gen de la distrofina por reacción en cadena de la polimerasa y se analizaron loa alelos polimórficos en los individuos estudiados. En 5/15 (33 por ciento) familias demostró la deleción de uno o varios exones. De las 68 mujeres, 27 (39,7 por ciento) resultaron portadoras, 27 (39,7 por ciento) no portadoras y en 14 (20,58 por ciento) no se pudo establecer un diagnóstico definitivo. En conclusión esta investigación pudo establecer el diagnóstico en 79,4 por ciento de las mujeres. Además en una familia se demostró que la mutación original ocurrió con el cromosoma X del abuelo materno, en otra se hizo el diagnóstico directo de portadora por hemicigosidad para el alelo mutado y en otra fue posible el diagnóstico prenatal. No se pudo excluir el mosaicismo germinal en 3 casos

Del(1)(q23) in a patient with Hutchinson-Gilford progeria.

A 9-year-old patient with the classical clinical picture of Hutchinson-Gilford progeria (HGP) is described. The karyotype shows a 46,XY,del(1)(q23) constitution. Our findings suggest that the interval 1q23 may play a roll in the etiology of HGP. A perturbation in glycosylation in connective tissue has been demonstrated in patients with this condition. This abnormality may be due to a defect in the UDP-galactose:beta-N-acetylglucosamina-beta-1,4-galactosyltransferase 3 (B4GALT3) gene that has been mapped in the interval 1q21-23. The cytogenetical analyses of this patient suggest that the B4GALT3 gene could be involved in the pathogenesis of HGP.

[Carrier detection of Duchenne/Becker muscular dystrophy by analysis of STRs loci linked to the gene of dystrophin in Venezuelan families]. / Detección de portadoras de distrofia muscular Duchenne/Becker a través del análisis de loci STRs ligados al gen de la distrofina en familias venezolanas.

The Duchenne/Becker Muscular Dystrophy (DMD/BMD) is an X linked recessive lethal disease. The female carrier will transmit the disease gene to half of her sons and half of her daughters; half of the daughters will be carriers, while half will be normal. Half of the sons will be normal and, on average, half will have the disease. It is of particular relevance to be able to detect carrier status among female relatives of the patients for genetic counseling and prenatal diagnosis. The method of Short Tandem Repeat (STR) sequence polymorphism analysis can determine haplotype at normal status or at risk status and, to establish genetic linkage between the mutated gene and the segregated haplotype. We have analyzed 105 members from 15 unrelated Venezuelan families with one or more siblings affected with DMD/DMB and 7 unrelated males. Of the 105, 37 were male (26 affected and 11 normal) and 68 were female. STR sequences (STR44, STR45, STR49, STR50, STR3'DYS) of the gene of the Dystrophin were amplified by polymerase chain reaction (PCR) to analyze allelic polymorphism in the families. Five of the 15 families (33%) had a deletion of one or several of the exons. Of the 68 females, 27 (39.7%) were carriers, 27 (39.7%) were non-carriers and in 14 cases (20.58%) it was not possible to reach a definitive diagnosis. The definitive diagnosis could be established in 79% of the females. This analysis also shows that the mutation occurred on the grandpaternal X chromosome in one family. Hemizygocity was detected and carrier status ascertained in the mother of other patient and in one family we were able to do prenatal diagnosis. The germinal mosaicism could not be excluded in 3 patients.

Hipoplasia de tibia, polidactilia y pulgar trifalángico: primera familia descrita en Venezuela / Hypoplasia of tibia polydactyly and triphalangeal thumbs: first family described in Venezuela

Werner en 1915, describió un paciente con las siguientes características: aplasia o hipoplasia bilateral de tibia, polidactilia y ausencia de pulgares. El modo de herencia es autosómico dominante, con expresividad variable. El objetivo de este trabajo es describir una niña en la que se demostró clínica y radiológicamente la presencia de signos compatibles con el diagnóstico de Hipoplasia de Tibia con Polidactilia. El estudio genealógico permite suponer que el gen tiene una expresividad variable, ya que por la línea materna se encontraron malformaciones tales como: sindactilia en manos, implantación proximal de pulgares y tibia vara. Se discuten los aspectos clínicos, radiológicos y genéticos

Diagnóstico molecular prenatal de fibrosis quística: reporte de tres casos / Prenatal diagnosis of cystic fibrosis: report of three cases

La fibrosis quística (FQ) es una enfermedad autosómica recesiva severa, causada por múltiples mutaciones en el gen RCTFQ. La mutación más frecuente en el mundo es la AF508, que consiste en la delección del codón que codifica a la fenilalanina en la posición 508. En este trabajo se presentan los primeros casos venezolanos de diagnóstico prenatal molecular en parejas de alto riesgo para tener descendencia con FQ. El diagnóstico molecular de la mutación AF508 se realizó en ADN extraído directamente de amnioticos o de células cultivadas y la aplicación de la Reacción de la Polimerasa (RCP) y electroforesis en gel de poliacrilamida. En los dos primeros casos, los fetos fueron homocigotos para el alelo AF508 y el tercer feto presentaba un alelo AF508, descartándose la homocigosis del alelo normal. El asesoramiento genético prenatal a estas parejas permitió que tomaran decisiones reproductivas objetivas en base al conocimiento del genotipo fetal, lo cual solo es posible con la aplicación de estas técnicas para el análisis del genoma