ClinVar

Hewett et al. (1994) described a patient with Marfan syndrome (MFS; 154700) who was heterozygous for a G-to-A transition at nucleotide 3952 in the FBN1 gene that resulted in a cys1223-to-tyr (C1223Y) substitution.

In a 7-year-old girl with typical ocular, skeletal, and cardiovascular features of Marfan syndrome but with additional features suggesting the diagnosis of Shprintzen-Goldberg syndrome (SGS; 182212), including hypotonia, scaphocephaly with craniosynostosis, low-set anomalous ears, hyperelastic skin, diastasis recti, vertical talus, and mental retardation, Dietz et al. (1995) found a G-to-A transition at nucleotide 3668, resulting in a C1223Y substitution within one of the repetitive EGF-like domains within fibrillin-1. The mutation occurred as a de novo event in heterozygous state and was not detected in over 100 chromosomes from control individuals. Although cysteine substitutions in EGF-like domains represent the most common class of mutations causing Marfan syndrome, no mutation causing Marfan syndrome had been found in the specific domain harboring C1223Y. The demonstration that fibrillin-1 is expressed as early as the 8-cell stage of human development was considered consistent with a possible role for fibrillin-1 in early craniofacial and CNS development. See Sood et al. (1996) for further details. Also see 134797.0045 for another patient with features of both disorders.