A De Novo novel mutation of the EDNRB gene in a Taiwanese boy with Hirschsprung disease.

Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of ganglion cells in the nerve plexuses of the lower digestive tract. Although mutations in eight different genes (EDNRB, EDN3, ECE1, SOX10, RET, GDNF, NTN, SIP1) have been identified in affected individuals, it is now clear that RET and EDNRB are the primary genes implicated in the etiology of HSCR. All eight genes are involved in the early development of the enteric nervous system, and most act through two distinct biochemical pathways mediated by RET and EDNRB. Mutations in RET and EDNRB account for up to 50% and 5% of HSCR cases in the general population, respectively. Interaction between these two signaling pathways could modify RET expression and, therefore, HSCR phenotype. Here, we report the case of a 1-year-old Taiwanese boy who presented with abdominal distension since birth and bilious vomiting after feeding. HSCR (short-segment type) was diagnosed based on X-ray, lower gastrointestinal series and biopsy findings. Mutation analysis revealed a heterozygous T>C missense mutation in exon 1 of the EDNRB gene, that substitutes the highly conserved cysteine-90 residue in the extracellular domain of the G protein-coupled receptor with an arginine residue (C90R). No RET gene mutation was detected in this patient.

Three novel EXT1 and EXT2 gene mutations in Taiwanese patients with multiple exostoses.

Multiple osteochondromatosis, also known as hereditary multiple exostoses (HME), is an inherited autosomal dominant disorder characterized by the presence of multiple exostoses on the long bones. These exostoses are benign cartilaginous tumors (enchondromata). Three different exostosis (EXT) loci on chromosomes 8q (exostosin 1, EXT1), 11p (exostosin 2, EXT2) and 19p (exostosin 3, EXT3) have been reported. Recently, the EXT1 and EXT2 genes were identified by positional cloning. Using polymerase chain reaction and direct sequencing, we analyzed the EXT1 and EXT2 genes in three familial cases and one sporadic case of HME in Taiwanese patients. We found three novel mutations (S277X in the EXT1 gene, and G194X and 939+1G>A in the EXT2 gene) and a known mutation (Q172X in the EXT2 gene). Mutation analysis in families with HME allows for genetic counseling and prenatal diagnosis.

The effect of normal saline irrigation at different temperatures on the surface of articular cartilage: an experimental study in the rat.

PURPOSE: To determine, with an electron microscope, the effects of irrigation fluid at different temperatures on the surface of articular cartilage. TYPE OD STUDY: Experimental in vivo study. METHODS: With a scanning electron microscope, we investigated the effect of 2 hours of irrigation with normal saline at 3 different temperatures (4 degrees C, 25 degrees C, and 37 degrees C) on articular hyaline cartilage in an in vivo rat knee model study. The contralateral knees were used as controls. We then compared the results. RESULTS: Specimens irrigated with cold (4 degrees C) fluid seemed to show the most uneven surface and apparent fibril exposure. Those irrigated with fluid close to body temperature (37 degrees C) showed the most even surface without fibril exposure. CONCLUSIONS: Although further work is needed to evaluate the long-term effects, using warm irrigation fluid to maintain the intra-articular environment at a more physiologically normal temperature may help reduce damage to cartilage during irrigation.

Anterior translation and morphologic changes of the ulnar nerve at the elbow in adolescent baseball players.

The effect of repetitive throwing on the ulnar nerve is not clear. There are no published imaging studies regarding this issue in adolescent baseball players. The purpose of this cross-sectional ultrasonographic study was to use 5- to 10-MHz frequency ultrasonography to define the anterior translation and flattening of the ulnar nerve in different elbow positions. We divided 39 adolescent baseball players into two groups, 19 pitchers and 20 fielders, according to the amount of throwing. Twenty-four non-athlete junior high school students were also included as controls. We ultrasonographically examined each participant's ulnar nerve in the cubital tunnel with the elbow extended and at 45°, 90° and 120° of flexion. Anterior translation and flattening of the ulnar nerve occurred in all groups. Pitchers had larger-scale anterior translation than did controls. In pitchers, the ulnar nerve exhibited more anterior movement on the dominant side than on the non-dominant side. The anterior subluxation of the ulnar nerve occurred in players without ulnar nerve palsy and was not correlated with elbow pain. In addition to the known musculoskeletal adaptations of pitchers' elbows, ultrasonography revealed new changes in the ulnar nerve, anterior translation and subluxation, after repetitive throwing. These changes might also be physiologic adaptations of throwing elbows.

A novel nonsense mutation of MSH2 gene in a Taiwanese family with hereditary nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant inherited disease predisposing to the development of colorectal cancers and several other malignancies (endometrium, ovaries, stomach, small bowel, hepatobiliary, and urinary tract). HNPCC is caused by germline mutations in any of the mismatch repair genes. Mutations in MLH1 and MSH2 account for almost 90% of all identified ones. Here, we report a Taiwanese family with HNPCC and mutation analysis revealed a novel nonsense mutation (S611X) in MSH2 gene.