RESUMO
Conotruncal anomaly face syndrome (CTAFS) was distinguished from velo-cardio-facial syndrome (VCFS) in a bind study, yet shared the finding of 22q11.2 deletions. This work has been extended to show that the 22q11.2 deletions in CTAFS greatly overlap those found in VCFS and many DiGeorge patients. The reason for dissimilar phenotypes with apparently similar 22q11.2 deletions is not yet known.
Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas/genética , Cromossomos Humanos Par 22/genética , Face/anormalidades , Cardiopatias Congênitas/genética , Deleção de Sequência , Anormalidades Múltiplas/classificação , Aberrações Cromossômicas/classificação , Transtornos Cromossômicos , Síndrome de DiGeorge/genética , Humanos , Hibridização in Situ Fluorescente , Fenótipo , SíndromeRESUMO
Two regions were chosen for linkage studies to cleft lip with or without cleft palate (CL[P]) because they are break points of a balanced translocation in a patient with severe bilateral facial clefting. We used dinucleotide repeats to test chromosomal regions 1q21 and 22q11.2 for such linkage. We studied three families with apparently dominantly inherited CL(P). Families #1 and #2 are local Caucasian families that have not been previously reported; family #3 is a Belgian family that has been previously published [DePaepe, 1989]. Significant evidence against close linkage of the dinucleotide repeats (D1S104, D22S156, D22S264) with CL(P) using a dominant model was obtained. Three other candidate regions were tested (2q37,4q31, and 8p) with the dinucleotide repeats PAX3, D4S175, and LPL respectively. The LOD scores generated at these three loci are not statistically significant for demonstrating negative linkage at these regions. However, they may be used with other informative families in the future, since LOD scores for the same model of inheritance may be added together. Negative or neutral LOD scores were generated at all informative loci using an autosomal dominant model with decreased penetrance.
Assuntos
Cromossomos Humanos Par 1 , Cromossomos Humanos Par 22 , Fenda Labial/genética , Fissura Palatina/genética , Sequência de Bases , Cromossomos Humanos Par 2 , Cromossomos Humanos Par 4 , Cromossomos Humanos Par 8 , Primers do DNA , Feminino , Genes Dominantes , Ligação Genética , Humanos , Escore Lod , Masculino , Modelos Genéticos , Dados de Sequência Molecular , Linhagem , Sequências Repetitivas de Ácido NucleicoRESUMO
An unusual family with Waardenburg syndrome type 1 (WSI), cleft lip (palate), and Hirschsprung disease is not linked to the PAX 3 gene since there is an obligate crossover which has occurred between PAX 3 DNA markers and the disorder in this family. This family may also have anticipation of the WSI traits as the proband's grandmother is nonpenetrant, his mother has dystopia canthorum, and severe cleft lip (palate), while the proband has dystopia canthorum, severe cleft lip (palate), and Hirschsprung disease. Thus, a locus other than PAX 3 is implicated in this Waardenburg-like syndrome with Hirschsprung disease and cleft lip (palate).
Assuntos
Fenda Labial/genética , Proteínas de Ligação a DNA/genética , Ligação Genética , Doença de Hirschsprung/genética , Fatores de Transcrição , Síndrome de Waardenburg/genética , Sequência de Bases , Fissura Palatina/genética , Feminino , Heterogeneidade Genética , Ligação Genética/genética , Marcadores Genéticos/genética , Haplótipos/genética , Humanos , Recém-Nascido , Masculino , Dados de Sequência Molecular , Fator de Transcrição PAX3 , Fatores de Transcrição Box Pareados , Linhagem , Sequências Repetitivas de Ácido Nucleico/genética , Síndrome de Waardenburg/classificaçãoRESUMO
A blind study was designed to test the hypothesis that some persons with a relatively rare cardiac malformation, pulmonary atresia with ventriculoseptal defect (PA/VSD), have a recognisable phenotype. Fourteen patients with cyanotic congenital heart lesions were examined by dysmorphologists blinded to the type of cardiac malformation. Six children were judged to have a similar craniofacial appearance; all had PA/VSD. These children were not originally considered to fall within the classic phenotypes of the DiGeorge sequence or the velocardiofacial syndrome, both of which have been shown to be associated with deletions of 22q11. More recently, 22q11 deletions have been documented in the conotruncal anomaly face syndrome and apparently isolated conotruncal heart defects. A new acronym, CATCH 22 syndrome (Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcaemia) has been suggested to encompass this very broad phenotypic spectrum. A preliminary molecular study was conducted using the dinucleotide repeat D22S264 located on chromosome 22q11.2. All cases tested with the subtle but recognisable phenotype had deletions, all lacking the maternal contribution at this locus, suggesting there may be a parent of origin effect.
