title: Mutations in SCARF2 are responsible for Van Den Ende-Gupta syndrome.
abstract: Van Den Ende-Gupta syndrome (VDEGS) is an extremely rare autosomal-recessive disorder characterized by distinctive craniofacial features, which include blepharophimosis, malar and/or maxillary hypoplasia, a narrow and beaked nose, and an everted lower lip. Other features are arachnodactyly, camptodactyly, peculiar skeletal abnormalities, and normal development and intelligence. We present molecular data on four VDEGS patients from three consanguineous Qatari families belonging to the same highly inbred Bedouin tribe. The patients were genotyped with SNP microarrays, and a 2.4 Mb homozygous region was found on chromosome 22q11 in an area overlapping the DiGeorge critical region. This region contained 44 genes, including SCARF2, a gene that is expressed during development in a number of mouse tissues relevant to the symptoms described above. Sanger sequencing identified a missense change, c.773G>A (p.C258Y), in exon 4 in the two closely related patients and a 2 bp deletion in exon 8, c.1328_1329delTG (p.V443DfsX83), in two unrelated individuals. In parallel with the candidate gene approach, complete exome sequencing was used to confirm that SCARF2 was the gene responsible for VDEGS. SCARF2 contains putative epidermal growth factor-like domains in its extracellular domain, along with a number of positively charged residues in its intracellular domain, indicating that it may be involved in intracellular signaling. However, the function of SCARF2 has not been characterized, and this study reports that phenotypic effects can be associated with defects in the scavenger receptor F family of genes.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Quebec H3A 1B1, Canada.
authors.forename: Natascia
authors.initials: N
authors.lastname: Anastasio
authors.forename: Tawfeg
authors.initials: T
authors.lastname: Ben-Omran
authors.forename: Ahmad
authors.initials: A
authors.lastname: Teebi
authors.forename: Kevin C H
authors.initials: KC
authors.lastname: Ha
authors.forename: Emilie
authors.initials: E
authors.lastname: Lalonde
authors.forename: Rehab
authors.initials: R
authors.lastname: Ali
authors.forename: Mariam
authors.initials: M
authors.lastname: Almureikhi
authors.forename: Vazken M
authors.initials: VM
authors.lastname: Der Kaloustian
authors.forename: Junhui
authors.initials: J
authors.lastname: Liu
authors.forename: David S
authors.initials: DS
authors.lastname: Rosenblatt
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.forename: Loydie A
authors.initials: LA
authors.lastname: Jerome-Majewska
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D016569:Blepharophimosis / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D009139:Musculoskeletal Abnormalities / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011780:Qatar; D051128:Scavenger Receptors, Class F / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013577:Syndrome
chemical_list: C469357:SCARF2 protein, human; D051128:Scavenger Receptors, Class F