Mutations inGRIP1cause Fraser syndrome

Abstract

Mutations in GRIP1 cause classic FS in humans.

Fraser Syndrome: Case Report With Review of Literature.

“…It is caused by mutation in FRAS 1 gene located on the long arm of chromosome 4 (4q21), FREM2 gene on chromosome 13, FREN1 and GPIP1. 5,6,12 It is inherited in autosomal recessive fashion. The term cryptophthalmos was introduced by Zehender et al 10 in 1872 who described a child whose eyes were covered by continuous sheets of skin from forehead to cheek, associated with additional malformations including hypertelorism, syndactyly, abnormal genitalia, umbilical hernia, anal stenosis and hoarse voice.…”

“…Fraser syndrome (FS) is an autosomal recessive condition with incidence of 0.043 per 10,000 live born infants and 1.1 in 10,000 stillbirths, making it a rare syndrome 3,4 . Mutations in FRAS1, FREN1, FREM2 and GPIP1 gene have been reported to underlie FS, indicating genetic heterogeneity 5,6 . These genes encode the extracellular matrix proteins that are necessary for the adhesion between basement membrane of epidermis and connective tissues of dermis during embryological development.…”

Complex translocation t(1;12;14)(q42;q14;q32) and HMGA2 deletion in a fetus presenting growth delay and bilateral cataracts

“…Lens degeneration is characteristic of eb, (Swiergiel et al, 2000) however several other anomalies are also associated. In humans, GRIP1 mutations were found to segregate with the Fraser syndrome as an autosomal recessive trait (Vogel et al, 2012), showing a severe phenotype including syndactyly and renal agenesis, notable during embryonic development. We speculate that a heterozygous alteration of this gene can be responsible for a milder phenotype, with lens impairment as a major feature.…”

AMACO Is a Component of the Basement Membrane–Associated Fraser Complex

“…The proteins are characterized by the shared presence of 12 CSPG repeats and single or multiple Calx-β domain(s) (Kiyozumi et al , 2007). In addition mutations in GRIP1 , which encodes a cytoplasmic scaffolding protein required for proper Fras1 localization at the BM (Takamiya et al , 2004; Long et al , 2008), result in classical FS (Vogel et al , 2012). Analysis of the mouse bleb mutants revealed transient embryonic epidermal blistering, particularly over the developing eyes and digits, as the likely primary defect leading to the later malformations characteristic of the human disorder (McGregor et al , 2003; Vrontou et al , 2003; Jadeja et al , 2005).…”

“…Despite the identification of mutations in FRAS1 , FREM2 and GRIP1 in both mice and humans with FS, a proportion of human cases remain unresolved suggesting that other genes may be involved (van Haelst et al , 2008; Vogel et al , 2012). Furthermore, phenotypic variation in Fraser syndrome points to the existence of common modifier genes (Slavotinek and Tifft, 2002).…”