ABSTRACT
We report on a 4 month old male infant with respiratory syncytial virus (RSV) infection leading to acute respiratory distress syndrome (ARDS). A diagnostic algorithm including extended infectiological and immunological work-up revealed absence of CD40-ligand. ARDS was treated successfully with a complex respiratory therapy plus intravenous immunoglobulin substitution. Molecular analysis detected mutations in the CD40L gene (Hyper-IgM syndrome Type 1). The case underlines the importance of an extended diagnostic work-up in an uncommonly severe course of respiratory infection in early infancy.
Subject(s)
CD40 Ligand/deficiency , CD40 Ligand/genetics , Cytomegalovirus Infections/diagnosis , Hyper-IgM Immunodeficiency Syndrome, Type 1/diagnosis , Opportunistic Infections/diagnosis , Respiratory Distress Syndrome/diagnosis , Respiratory Syncytial Virus Infections/diagnosis , Algorithms , Critical Care/methods , Cytomegalovirus Infections/genetics , Cytomegalovirus Infections/therapy , DNA Mutational Analysis , Diagnosis, Differential , Exons , Humans , Hyper-IgM Immunodeficiency Syndrome, Type 1/genetics , Hyper-IgM Immunodeficiency Syndrome, Type 1/therapy , Infant , Male , Opportunistic Infections/genetics , Opportunistic Infections/therapy , Respiratory Syncytial Virus Infections/genetics , Respiratory Syncytial Virus Infections/therapyABSTRACT
Mental retardation is the most frequent cause of serious handicap in children and young adults. The underlying causes of this heterogeneous condition are both acquired and genetically based. A recently performed refinement of the linkage interval in a large Belgian family with mild to severe non-syndromic X linked mental retardation, classified as MRX9, revealed a candidate region of 11.3 Mb between markers DXS228 and DXS1204 on the short arm of the X chromosome. In order to identify the underlying disease gene in the MRX9 family, we established a gene catalogue for the candidate region and performed comprehensive mutation analysis by direct sequencing. A human homologue of the bacterial 23S rRNA methyltransferase Fstj, the FTSJ1 gene, is located within this region and displayed a sequence alteration in the conserved acceptor splice site of intron 3 (IVS3-2A>G) in all tested patients and carrier females of this family. In contrast, it was absent in all unaffected male family members tested. The mutation results in skipping of exon 4 and introduces a premature stop codon in exon 5, probably leading to a severely truncated protein. Our finding indicates that a protein, possibly associated with ribosomal stability, can be linked to X linked mental retardation (XLMR).
Subject(s)
Chromosomes, Human, X/genetics , Intellectual Disability/genetics , Methyltransferases/genetics , Mutation/genetics , Nuclear Proteins/genetics , RNA Splice Sites/genetics , Amino Acid Sequence , Belgium , Female , Humans , Male , Methyltransferases/chemistry , Molecular Sequence Data , Nuclear Proteins/chemistry , Pedigree , RNA, Messenger/analysis , RNA, Messenger/geneticsABSTRACT
An Austrian family with nonsyndromic X-linked mental retardation (MRX) is reported in which the obligatory carrier females are normal, and 5 affected males have mild to moderate mental retardation. Linkage analysis indicated an X pericentromeric localization, with flanking markers DXS989 and DXS1111 and a maximum multipoint LOD score of 2.09 (straight theta = 0) for the 7 cosegregating markers DXS1243, CybB, MAOB, DXS988, ALAS2, DXS991, and AR. MRX58 thus mapped within a 50-cM interval between Xp11.3 and Xq13.1 and overlapped with 23 other MRX families already described. This pericentromeric clustering of MRX families suggests allelism, with a minimum of 2 X-linked mental retardation (XLMR) genes in this region.
Subject(s)
Intellectual Disability/genetics , X Chromosome/genetics , Centromere/genetics , Chromosome Mapping , Cytogenetics , Family Health , Female , Genetic Linkage , Humans , Lod Score , Male , Microsatellite Repeats , PedigreeABSTRACT
History case of a patient treated for a bilateral orbital inflammatory pseudotumor has been rehospitalised for generalised lymphoma, despite the histological features of this tumor which evoked a pseudo-tumor. This error seems to be frequent because of the difficulties for the histological investigation of the tumor. Actually the application of immunohistochemical techniques and the study of immunoglobulin gene DNA rearrangement patterns allows the diagnosis. Often most of the orbital lymphomas, though apparently isolated, represent a localization of a systemic disease. Their treatment consists in either of radiotherapy in low grade malignancy localized cases or in chemotherapy in the others sometimes associated to radiotherapy.
