title: Mutational analysis of two boys with the severe perinatally lethal Melnick-Needles syndrome.
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. (
authors.affiliation: Serviço Especial de Genética, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Helena H
authors.initials: HH
authors.lastname: Santos
authors.forename: Paula P
authors.initials: PP
authors.lastname: Garcia
authors.forename: Latife
authors.initials: L
authors.lastname: Pereira
authors.forename: Letícia L
authors.initials: LL
authors.lastname: Leão
authors.forename: Regina A P L
authors.initials: RA
authors.lastname: Aguiar
authors.forename: Ana M A
authors.initials: AM
authors.lastname: Lana
authors.forename: Maria Raquel S
authors.initials: MR
authors.lastname: Carvalho
authors.forename: Marcos J B
authors.initials: MJ
authors.lastname: Aguiar
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000328:Adult; D019943:Amino Acid Substitution; D001483:Base Sequence; D003285:Contractile Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D017809:Fatal Outcome; D005260:Female; D064448:Filamins; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D013577:Syndrome
chemical_list: D003285:Contractile Proteins; D017931:DNA Primers; D064448:Filamins; D008840:Microfilament Proteins