Disease relevance of FRAS1

• Fraser and Ablepharon macrostomia phenotypes: Concurrence in one family and association with mutated FRAS1 [1].
• Fraser syndrome (OMIM 219000) is a multisystem malformation usually comprising cryptophthalmos, syndactyly and renal defects [2].
• Identification of a new gene mutated in Fraser syndrome and mouse myelencephalic blebs [3].
• Three additional cases of pulmonary hyperplasia in the Fraser syndrome were ascertained from a review [4].
• Fused eyelids, airway anomalies, ovarian cysts, and digital abnormalities in siblings: a new autosomal recessive syndrome or a variant of Fraser syndrome [5]?

Psychiatry related information on FRAS1

• The child was diagnosed to have Fraser syndrome (cryptophthalmos, abnormal genitalia, mental deficiency, renal agenesis and abnormal ears) [6].

High impact information on FRAS1

• Two individuals with Fraser syndrome were homozygous with respect to the same missense mutation of FREM2, confirming genetic heterogeneity [3].
• Fraser syndrome is a recessive, multisystem disorder presenting with cryptophthalmos, syndactyly and renal defects and associated with loss-of-function mutations of the extracellular matrix protein FRAS1 [3].
• This is the only missense mutation reported in any blebbing mutant or individual with Fraser syndrome, suggesting that calcium binding in the CALXbeta-cadherin motif is important for normal functioning of FREM2 [3].
• In one animal model of Fraser syndrome, the eye-blebs (eb) mouse, Grip1 is disrupted by a deletion of two coding exons [7].
• Mutation analysis identified five frameshift mutations in FRAS1, which encodes one member of a family of novel proteins related to an extracellular matrix (ECM) blastocoelar protein found in sea urchin [2].

Chemical compound and disease context of FRAS1

• OBJECTIVE: To evaluate disease-specific cardiovascular reactivity patterns in patients with fibromyalgia (FM) using a recently described method called fractal and recurrence analysis score (FRAS) [8].

Biological context of FRAS1

• Spatiotemporal distribution of Fras1/Frem proteins during mouse embryonic development [9].
• Here we report autozygosity mapping and show that the locus FS1 at chromosome 4q21 is associated with Fraser syndrome, although the condition is genetically heterogeneous [2].
• Fraser syndrome is rare and the FRAS1 gene has 75 exons, complicating mutation screening in affected patients [10].
• Sonography permitted the diagnosis of Fraser syndrome (cryptophthalmos-syndactyly syndrome) at 18.5 weeks of gestation in a fetus whose parents had had a previous affected child [11].
• The histopathologic findings in Fraser syndrome at this gestational age, in particular the eye and ear, have not been described previously [11].

Anatomical context of FRAS1

• The similarity of the phenotypic characteristics among the bleb mouse mutants, together with the fact that Fras1/Frem proteins are co-localized in embryonic epithelial basement membranes, suggest that they operate in a common pathway [9].
• In sum, our data suggest that perturbations in the composition of the extracellular space underlying epithelia could account for the onset of the blebbed phenotype in mouse and Fraser syndrome manifestation in human [12].
• Thus, our findings identify Fras1 as an important structural component of the sub-lamina densa of basement membranes required for lobar septation and the organization of blood capillaries in the peripheral lung [13].
• Expression of Fras1 was detected in the mesothelial cells of the visceral pleura and in the conducting airway epithelia [13].
• We demonstrate that loss of Fras1 causes alterations in the molecular composition of basement membranes, concomitant with local disruptions of epithelial-endothelial contacts and extravasation of erythrocytes into the embryonic respiratory lumen [13].

Associations of FRAS1 with chemical compounds

• Based on these predictors, the "Fractal & Recurrence Analysis-based Score" (FRAS) was calculated: FRAS=76.2+0.04*HR-supine-DET -12.9*HR-tilt-R/L -0.31*HR-tilt-s.d. -19.27*PTT-tilt-R/L -9.42*PTT-tilt-WAVE [14].
• However, the induction of the chronic AP-1 complex and the chronic Fras provides a mechanism capable of underlying long-lasting alterations in gene expression following chronic cocaine treatment [15].

Other interactions of FRAS1

• Several of the additional symptoms present in the second sib were suggestive of Fraser syndrome, but the severe microcephaly in both sibs is unusual [16].

Analytical, diagnostic and therapeutic context of FRAS1

• Here, we report for the first time the immunofluorescence pattern of Frem3 and provide a comparative analysis of the spatiotemporal localization of all Fras1/Frem proteins during mouse embryonic development [9].
• Prenatal diagnosis of Fraser syndrome at 18.5 weeks gestation, with autopsy findings at 19 weeks [11].
• A 16-year-old girl with Fraser syndrome underwent abdominal hysterectomy under general anaesthesia [17].
• We reviewed the differential diagnosis of fused eyelids, airway anomalies, and ovarian cysts, and the manifestations resemble those seen in Fraser syndrome [5].
• Resuscitation failure due to Fraser syndrome in a newborn undiagnosed in the prenatal period [18].

References