Here I present: “Schwartz-Jampel Syndrome”, Victor McKusick, Mendelian Inheritance in Man’, 1966. Schwartz-Jampel Syndrome is caused by a mutation in the PERLECAN protein (shown ABOVE).
INTRODUCTION.
Schwartz-Jampel syndrome is a condition characterized by permanent muscle stiffness (myotonia) and bone abnormalities known as chondrodysplasia. The signs and symptoms of this condition become apparent sometime after birth, usually in early childhood. Either muscle stiffness or chondrodysplasia can appear first. The muscle and bone abnormalities worsen in childhood, although most affected individuals have a normal lifespan. The specific features of Schwartz-Jampel syndrome vary widely.
Myotonia involves continuous tensing (contraction) of muscles used for movement (skeletal muscles) throughout the body. This sustained muscle contraction causes stiffness that interferes with eating, sitting, walking, and other movements. Sustained contraction of muscles in the face leads to a fixed, “mask-like” facial expression with narrow eye openings (blepharophimosis) and pursed lips. This facial appearance is very specific to Schwartz-Jampel syndrome. Affected individuals may also be nearsighted and experience abnormal blinking or spasms of the eyelids (blepharospasm).
Chondrodysplasia affects the development of the skeleton, particularly the long bones in the arms and legs and the bones of the hips. These bones are shortened and unusually wide at the ends, so affected individuals have short stature. The long bones may also be abnormally curved (bowed). Other bone abnormalities associated with Schwartz-Jampel syndrome include a protruding chest (pectus carinatum), abnormal curvature of the spine, flattened bones of the spine (platyspondyly), and joint abnormalities called contractures that further restrict movement.
COMMENTS.
Schwartz–Jampel syndrome (SJS) is a genetic disease caused by a mutation in the perlecan gene (HSPG2) which causes osteochondrodysplasia associated with myotonia. Most people with Schwartz–Jampel syndrome have a nearly normal life expectancy.
Perlecan also known as basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) or heparan sulfate proteoglycan type-2 (HSPG2), is a protein that in humans is encoded by the HSPG2 gene. The HSPG2 gene codes for a 4,391 amino acid protein with a molecular weight of 468,829. Perlecan is one of the largest known proteins.
There is evidence that Schwartz-Jampel syndrome type-1 (SJS1) is caused by homozygous or compound heterozygous mutation in the gene encoding perlecan (HSPG2) on cytogenetic location 1p36.12 and genomic coordinates 1:21,822,244-21,937,310 . The screenshot of the HSPG2 gene 115,067 bp (base pairs) of DNA sequence length is shown BELOW. Nine (9) other genes besides HSPG2 in the 1p36.12 cytogenetic location are listed BENEATH.
| Coordinate | Symbol | Genomic Name. |
| 1:21,436,789 | NBPF3 | Neuroblastoma breakpoint family, member 3 |
| 1:21,508,984 | ALPL | Alkaline phosphatase, liver/bone/kidney |
| 1:21,596,221 | RAP1GA1 | RAP1, GTPase activating protein 1 |
| 1:21,678,298 | USP48 | Ubiquitin-specific peptidase 48 |
| 1:21,822,244 | HSPG2 | Heparan sulfate proteoglycan of basement membrane |
| 1:21,977,022 | CELA3B | Chymotrypsin-like elastase 3A |
| 1:22,001,657 | CELA3A | Chymotrypsin-like elastase 3A |
| 1:22,052,709 | CDC42 | Cell division cycle 42 (GTP-binding protein, 25kD) |
| 1:22,117,313 | WNT4 | Wingless-type MMTV integration site family, member 4 |
| 1:22,428,909 | ZBTB40 | Zinc finger- and BTB domain-containing protein 40 |
