1/5. Dominant paternal transmission of Cornelia de lange syndrome: a new case and review of 25 previously reported familial recurrences.The Cornelia de lange syndrome (CdLS) is an autosomal dominant multisystem disorder characterized by somatic and cognitive retardation, characteristic facial features, limb abnormalities, hearing loss, and other organ system involvement. The vast majority of cases (99%) are sporadic, with rare familial occurrences having been reported. Most individuals with CdLS do not reproduce as a result of the severity of the disorder. Maternal transmission has been well documented, as have several cases of multiple-affected children being born to apparently unaffected parents. Paternal transmission has rarely been reported. A case is reported here of a father with classic features of CdLS with a similarly affected daughter. A review of the reported familial cases of CdLS is summarized.- - - - - - - - - - ranking = 1keywords = transmission (Clic here for more details about this article) |
2/5. Father-to-daughter transmission of Cornelia de lange syndrome caused by a mutation in the 5' untranslated region of the NIPBL Gene.Cornelia de lange syndrome (CdLS; also called Brachmann de lange syndrome) is a developmental disorder characterized by typical facial dysmorphism, growth and mental retardation, microcephaly, and various malformations. Mutations in the NIPBL gene have been identified in approximately 40% of reported cases, suggesting either genetic heterogeneity or that some NIPBL mutations are not detected by current screening strategies. We screened a cohort of 21 patients with no previously identified NIPBL anomaly for mutations in the 5' untranslated region (5'UTR) and the proximal promoter of the NIPBL gene. We identified a heterozygous deletion-insertion mutation in exon 1, 321 nucleotides upstream of the translation initiation codon (c.-321_-320delCCinsA) in one affected girl and her mildly affected father. This mutation altered highly conserved nucleotides, was not found in 400 control alleles, arose de novo in the father, and cosegregated with the disease in the family. Using real-time quantitative PCR, we showed that NIPBL mRNA expression was lowered in patients' lymphocytes compared to control samples. Finally, we showed that, when subcloned into a luciferase reporter vector, the mutation leads to a significant reduction of reporter gene activity. Our results demonstrate that mutations in the 5' noncoding region of the NIPBL gene can be involved in the pathogenesis of CdLS. Mutations affecting this region of the gene might be associated with a milder phenotype.- - - - - - - - - - ranking = 0.66666666666667keywords = transmission (Clic here for more details about this article) |
3/5. male-to-male transmission of mild Brachmann-de lange syndrome.We report on a father and son with mild Brachmann-de lange syndrome. Previous reports have documented apparent autosomal dominant transmission; however, only one example of male-to-male transmission of possible Brachmann-de lange syndrome has been reported. This case provides further evidence of the existence of an autosomal dominant form of Brachmann-de lange syndrome.- - - - - - - - - - ranking = 1keywords = transmission (Clic here for more details about this article) |
4/5. Autosomal dominant inheritance of Brachmann-de lange syndrome.A mother with mild phenotype and her severely affected son, both with classic manifestations of Brachmann-de lange syndrome (BDLS), are described. This documented mother-to-child transmission supports the hypothesis of autosomal dominant transmission with intrafamilial variability. Known cases of BDLS with autosomal dominant inheritance are reviewed. Although most cases of BDLS are sporadic, a careful evaluation of parents of affected children is important for appropriate genetic counseling.- - - - - - - - - - ranking = 0.33333333333333keywords = transmission (Clic here for more details about this article) |
5/5. Brachmann-de lange syndrome: autosomal dominant inheritance and male-to-male transmission.We report on familial occurrence of the Brachmann-de lange syndrome (BDLS): a mildly affected father and his severely affected son and daughter who have different mothers. Both children are severely affected while the father has a much milder but definite BDLS phenotype. Our report documents the third example of male-to-male transmission and adds to the argument against exclusively maternal transmission in familial cases. In addition, our findings illustrate the occurrence of severe manifestations in cases of familial BDLS.- - - - - - - - - - ranking = 1keywords = transmission (Clic here for more details about this article) |