ABSTRACT
Melnick-Needles syndrome (MNS) (OMIM 309350) is a rare, X-linked dominant condition, caused by mutations in the filamin A gene (FLNA, on Xq28). In females, the syndrome presents with bone dysplasia and characteristic facial changes. Affected males may show two different phenotypes. One is similar to the female phenotype and is seen in children born to unaffected mothers and suggesting new mutations. Alternatively, males born to affected mothers have an embryonic or perinatally lethal disorder. It has been claimed that MNS constitutes part of a spectrum including frontometaphyseal dysplasia, otopalatodigital syndrome type 1 (OPD1) and otopalatodigital syndrome type 2 (OPD2). These conditions are produced by different mutations in the filamin A gene (FLNA). MNS is caused by three different mutations in FLNA exon 22, to date detected only in females. We describe the clinical manifestations and present the results of FLNA exon 22 mutations screening in two boys with the perinatally lethal form of MNS and their affected mothers. In order to obtain DNA amplification from paraffin-embedded tissues, we designed a new method based on hemi-nested PCR. One of the children (and his mother) had a previously undescribed mutation produced by a double SNP in the positions 3776 and 3777 of the gene and leading to an amino acid substitution (NP_001447:p.[Gly1176Asp]). The second child (and his mother) had an already known mutation (NP_001447.2:p[.Ser1199Leu]). This is the first report confirming the presence FLNA mutations in boys with the perinatally lethal phenotype of MNS. (
Subject(s)
Abnormalities, Multiple/genetics , Contractile Proteins/genetics , Genetic Diseases, X-Linked/genetics , Microfilament Proteins/genetics , Osteochondrodysplasias/genetics , Abnormalities, Multiple/pathology , Adult , Amino Acid Substitution , Base Sequence , DNA Mutational Analysis/methods , DNA Primers/genetics , Exons , Fatal Outcome , Female , Filamins , Genetic Diseases, X-Linked/pathology , Humans , Infant, Newborn , Male , Osteochondrodysplasias/pathology , Phenotype , Polymerase Chain Reaction/methods , Polymorphism, Single Nucleotide , Pregnancy , SyndromeABSTRACT
OBJECTIVE: To compare the prevalence of depression among mothers of children with asthma and mothers of children without asthma and to investigate the influence of severity and duration of childhood asthma on maternal depression. METHOD: A cross-sectional study including 80 mothers of children with asthma and 160 mothers of children without asthma who attended the pediatric outpatient clinics of a teaching hospital in Southern Brazil. The main outcome measure was the presence of depression in these mothers, measured by the Beck Depression Inventory. RESULTS: The prevalence of depression was higher among mothers of asthmatic children compared with mothers of non-asthmatic children (43.8% vs. 17.5%, p < 0.001), with an adjusted prevalence ratio of 2.74 (95% confidence interval [CI] 1.76-4.25). Mothers of children with persistent asthma had a higher prevalence of depression than mothers of children with intermittent asthma (62.8% vs. 21.6%, p < 0.001), with an adjusted prevalence ratio of 2.77 (95% CI: 1.46-5.27). No significant association was observed between duration of childhood asthma and maternal depression. CONCLUSION: Mothers of children with asthma have a higher prevalence of depression than mothers of children without asthma. The severity but not duration of childhood asthma is associated with maternal depression.
