Familial neonatal Marfan syndrome due to parental mosaicism of a missense mutation in the FBN1 gene

• Published in: American journal of medical genetics. Part A Vol. 143A; no. 8; pp. 875 - 880
• Main Authors: Tekin, Mustafa, Cengiz, Filiz Başak, Ayberkin, Eda, Kendirli, Tanıl, Fitoz, Suat, Tutar, Ercan, Çiftçi, Ergin, Conba, Atakan
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-04-2007; Wiley-Liss
• Subjects: Biological and medical sciences; Chronic obstructive pulmonary disease, asthma; cysteine residue; emphysema; Family Health; Fatal Outcome; Fibrillin-1; Fibrillins; Genetic Counseling; Heterozygote; Humans; Infant, Newborn; Male; Marfan Syndrome - diagnosis; Marfan Syndrome - genetics; Medical genetics; Medical sciences; Microfilament Proteins - genetics; Mosaicism; Mutation, Missense; neonatal Marfan syndrome; Pneumology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin disease; Cysteine; Neonatal; Parent; cysteine residue; neonatal Marfan syndrome; Marfan syndrome; Missense mutation; Gene; Systemic disease; Bronchus disease; Obstructive pulmonary disease; Human; Lung disease; Connective tissue disease; Thiol; Elastic tissue disease; Respiratory disease; Family study; fibrillin-1; Genetic disease; Sulfur containing aminoacid; Newborn; Mosaicism; Emphysema
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.31660

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. © 2007 Wiley‐Liss, Inc.