title: Phenotypic overlap in Melnick-Needles, serpentine fibula-polycystic kidney and Hajdu-Cheney syndromes: a clinical and molecular study in three patients.
abstract: Several disorders characterized primarily by anomalies of the skeleton have recently been shown to be caused by mutations in the X-linked gene, FLNA. One of these conditions, the Melnick-Needles syndrome exhibits a phenotype that shares overlap with that of serpentine fibula-polycystic kidney syndrome and the autosomal dominant condition, Hajdu-Cheney syndrome. Here, we describe three individuals with these diagnoses. The individual with serpentine fibula-polycystic kidney syndrome, the fifth case reported in the literature, exhibited wormian bones which further expands the phenotypic spectrum for this condition and extends the overlap with Hajdu-Cheney syndrome. All three members of the filamin gene family, FLNA, and its functionally related paralogues, FLNB and FLNC, were screened for pathogenic mutations in all three individuals. We found a mutation in FLNA in the individual with Melnick-Needles syndrome, but no pathogenic variants in any filamin gene in the two individuals with Hajdu-Cheney syndrome and serpentine fibula-polycystic kidney syndrome. Clinical and molecular evidence indicates that Melnick-Needles syndrome is aetiologically distinct from Hajdu-Cheney syndrome and serpentine fibula-polycystic kidney syndrome, but these two latter conditions share many clinical similarities and may prove to be allelic to one another.
authors.affiliation: Genetics Unit Radiology of Instituto da Cariança of University, São Paulo, Brazil Department of Paediatrics and Child Health, University of Otago, Dunedin, New Zealand.
authors.forename: Lilian M J
authors.initials: LMJ
authors.lastname: Albano
authors.forename: Débora R
authors.initials: DR
authors.lastname: Bertola
authors.forename: Mário F
authors.initials: MF
authors.lastname: Barba
authors.forename: Marcelo
authors.initials: M
authors.lastname: Valente
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Robertson
authors.forename: Chong A
authors.initials: CA
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D003285:Contractile Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D064448:Filamins; D031845:Hajdu-Cheney Syndrome / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000473:pathology
chemical_list: D003285:Contractile Proteins; C578662:FLNB protein, human; C578661:FLNC protein, human; D064448:Filamins; D008840:Microfilament Proteins