title: Familial neonatal Marfan syndrome due to parental mosaicism of a missense mutation in the FBN1 gene.
abstract: We present a family in which three siblings were born with neonatal Marfan syndrome (MFS) to unaffected parents. The clinical findings included joint contractures, large ears, loose skin, ectopia lentis, muscular hypoplasia, aortic root dilatation, mitral and tricuspid valve insufficiency, and pulmonary emphysema. All three siblings died due to cardiorespiratory insufficiency by 2-4 months of age. Screening of the FBN1 gene showed the heterozygous c.3257G > A (p.Cys1086Tyr) mutation in the proband. Mosaicism of the mutation was demonstrated in the somatic cells and in the germ line of the father. Although three examples of parental mosaicism for classical MFS were demonstrated previously, this is the first report of familial occurrence of neonatal MFS due to a heterozygous mutation in FBN1. In conclusion, the p.Cys1086Tyr mutation in FBN1 is consistently associated with neonatal MFS. Parental mosaicism should always be kept in mind when counseling families with MFS.
authors: Division of Clinical Molecular Pathology and Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey. mtekin@medicine.ankara.edu.tr
authors: Mustafa
authors: M
authors: Tekin
authors: Filiz Başak
authors: FB
authors: Cengiz
authors: Eda
authors: E
authors: Ayberkin
authors: Tanil
authors: T
authors: Kendirli
authors: Suat
authors: S
authors: Fitoz
authors: Ercan
authors: E
authors: Tutar
authors: Ergin
authors: E
authors: Ciftçi
authors: Atakan
authors: A
authors: Conba
mesh_terms: D005192:Family Health; D017809:Fatal Outcome; D000071838:Fibrillin-1; D000071837:Fibrillins; D005817:Genetic Counseling; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D009030:Mosaicism; D020125:Mutation, Missense; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines