A novel fibrillin 1 gene mutation leading to marfan syndrome with minimal cardiac features.

Marfan syndrome is an autosomal dominant disorder of the connective tissue, characterized by early development of thoracic aortic aneurysms and/or dissections, accompanied by ocular and/or skeletal involvement, and is caused by mutations in the fibrillin 1 (FBN1) gene. We report on a patient with ectopia lentis and a nonprogressive aortic root dilatation who presented with a novel mutation affecting a conserved cysteine residue present in a calcium-binding epidermal growth factor-like domain of FBN1 (ENSP00000325527, p.Cys538Phe; Chr15:48,805,751 G>T), as revealed by complete sequencing of the FBN1 gene exons and flanking sequences. Identification of the mutation led to genetic screening of apparently asymptomatic family members, allowing the detection of characteristic ocular phenotypes in the absence of typical cardiac Marfan features. This finding stresses the importance of genetic screening of asymptomatic relatives for FBN1 gene mutation carriers.

Novel Frameshift CHD7 Mutation Related to CHARGE Syndrome.

CHARGE syndrome is a rare congenital condition characterized by 6 cardinal features: coloboma, heart defect, atresia choanae, retarded growth and development, genital anomalies, and ear anomalies/deafness. Mutations of the chromodomain helicase DNA-binding protein gene CHD7 are reported to be a major cause of CHARGE syndrome. Herein, we report the case of a 27-year-old patient presenting with typical symptoms who bears a novel heterozygous insertion in exon 2 of the CHD7 gene (c.327dupC) resulting in an amino acid substitution and a frameshift (p.Val110Argfs*22) that leads to a 131-amino-acid truncated polypeptide, likely representing a null allele. Parental genetic screening confirmed the sporadic origin of the mutation.