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: Natascia Anastasio, Tawfeg Ben-Omran, Ahmad Teebi, Kevin C H Ha, Emilie Lalonde, Rehab Ali, Mariam Almureikhi, Vazken M Der Kaloustian, Junhui Liu, David S Rosenblatt, Jacek Majewski, Loydie A Jerome-Majewska
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 87 Issue 4 Pg. 553-9 (Oct 08 2010) ISSN: 1537-6605 [Electronic] United States
• PMID: 20887961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Chemical References

• SCARF2 protein, human
• Scavenger Receptors, Class F

Topics

• Abnormalities, Multiple (genetics)
• Amino Acid Sequence
• Base Sequence
• Blepharophimosis (genetics)
• Chromosomes, Human, Pair 22 (genetics)
• Ethnicity (genetics)
• Female
• Genes, Recessive
• Genotype
• Humans
• Male
• Microarray Analysis
• Molecular Sequence Data
• Musculoskeletal Abnormalities (genetics)
• Mutation, Missense (genetics)
• Pedigree
• Polymorphism, Single Nucleotide (genetics)
• Qatar
• Scavenger Receptors, Class F (genetics, metabolism)
• Sequence Analysis, DNA
• Syndrome