ABSTRACT
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.
Subject(s)
Abnormalities, Multiple/genetics , Lumbar Vertebrae/abnormalities , Lymphocyte Activation/genetics , Abnormalities, Multiple/diagnostic imaging , Abnormalities, Multiple/embryology , Female , Humans , Infant, Newborn , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/embryology , Morphogenesis , Radiography , SyndromeABSTRACT
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
Subject(s)
Humans , Male , Female , Pregnancy , Dystrophin , Muscular Dystrophy, Duchenne , X ChromosomeABSTRACT
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.