The gene for a human microfibril-associated glycoprotein is commonly deleted in Smith-Magenis syndrome patients.
Smith-Magenis syndrome (SMS) is a clinically recognizable multiple congenital anomaly/mental retardation syndrome associated with deletion of chromosome 17p11.2. Here we report the identification of a novel gene encoding a human microfibril-associated glycoprotein (MFAP4), which has been mapped to the SMS region. A full-length cDNA corresponding to this gene has been sequenced, and reveals a coding region of 255 amino acids. MFAP4 has a fibrinogen-like domain and shares a high level of sequence homology to a fragment of a bovine 36 kDa microfibril-associated glycoprotein. The N-terminus of the protein bears an Arg-Gly-Asp sequence that serves as the ligand motif for cell surface receptor integrin. These structural features of MFAP4 suggest that it is an extracellular matrix protein involved in cell adhesion or intercellular interactions. Deletion analysis has been conducted on 31 SMS patients by polymerase chain reaction and Southern analysis of somatic cell hybrids retaining the del(17)(p11.2) chromosome or by fluorescence in situ hybridization. The MFAP4 locus is deleted in 30 of 31 SMS patients. Thus, the function of this gene must be considered in the pathogenesis of SMS. Given our previous hypothesis that SMS is a contiguous gene syndrome, complete and exhaustive definition of the critical deletion interval and a thorough phenotype-genotype correlation is required to demonstrate the role and importance of the MFAP4 gene in SMS.
Zhao
Z
Z
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Lee
C C
CC
Jiralerspong
S
S
Juyal
R C
RC
Lu
F
F
Baldini
A
A
Greenberg
F
F
Caskey
C T
CT
Patel
P I
PI
D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003285:Contractile Proteins / Q000235:genetics*; D018076:DNA, Complementary; D004547:Elastic Tissue / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D017353:Gene Deletion; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008969:Molecular Sequence Data; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013577:Syndrome
D003285:Contractile Proteins; D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; C016598:microfibrillar protein