Clinical and molecular characteristics of Thai patients with achondroplasia.

Achondroplasia is an autosomal dominant disorder characterized by disproportionately short stature, frontal bossing, rhizomelia, and trident hands. Most patients appear sporadically resulting from a de novo mutation associated with advanced paternal age. A glycine to arginine mutation at codon 380 (G380R) of the fibroblast growth factor receptor 3 gene (FGFR3) was found to be the most common cause of achondroplasia in various populations. We identified and clinically characterized 3 Thai patients with achondroplasia. In all of them, we also successfully identified the G380R mutation supporting the observation that this is the most common mutation in achondroplasia across different ethnic groups including Thai.

Prenatal prediction of spinal muscular atrophy by SMN deletion analysis.

The objective of this study was to provide prenatal prediction of spinal muscular atrophy (SMA) by survival motor neuron (SMN) gene deletion analysis and genetic counseling in families with previous child affected with SMA. The SMN gene is absent or interrupted in approximately 95% of SMA patients independence of clinical severity. We study four families with one previous child affected in each by performing the SMN deletion analysis in the index case. When a homozygous deletion in exon 7 or exon 8 is found, we offer prenatal prediction to the family. All four index cases had homozygous deletions of the SMN gene. Prenatal diagnosis by amniocentesis was performed in all pregnancies. Two pregnancies were positive for the homozygous deletion of the SMN gene, non-directive counseling was given and the two pregnancies were terminated. The other two pregnancies showed no deletion of the SMN gene. The unborn child is yet to be followed up. The prenatal prediction of SMA shows considerable requirements and potential effectiveness in prevention of the SMA in families at risk which cut the cost of care in this incurable disease.

Squamous cell carcinoma of head and neck.

Head and neck cancers are a major heath problem and common malignancies in Thailand. Up to 80 per cent of cases are caused by smoking and alcohol consumption. Epithelial mucosa of the aerodigestive tract exposed to carcinogens results in cellular mutations at different areas by a process called field cancerization and causes multistep carcinogenesis. Over 90 per cent of cases are squamous cell carcinoma. Prognostic factors depend on the patients, diseases and treatment. Currently, several molecular pathogenesis have been discovered such as abnormalities of c-myc, c-ras, c-erbB-1, bcl, int-2, hst1 oncogenes, p53 and p16 tumor suppressor genes. Common chromosomal abnormalities are 3p, 9p, 11q, 13q, 17p. Diagnosis requires symptoms and signs, radioimaging, and pathology. Stage I and II can be treated by surgery or radiotherapy. However, stage II requires and combination of surgery and radiotherapy, and studies of chemotherapy and local treatment to increase therapeutic efficacy by several approaches such as combination chemotherapy, new drugs, and biologic therapy.

Loss of heterozygosity for chromosome 11 in Epstein-Barr-virus associated nasopharyngeal carcinoma.

In order to demonstrate and define possible tumor suppressor gene loci on chromosome 11 associated with NPC, we used 7 STR to test for LOH on 25 NPC samples. LOH was detected in 46 per cent of cases. Most LOH loci were clustered on the long arm. Further study demonstrated 22 per cent and 45.5 per cent of cases with LOH on 11q13 and 11q23 respectively.

Diagnosis and carrier detection in a Duchenne muscular dystrophy family by multiplex polymerase chain reaction and microsatellite analysis.

We used multiplex PCR and a microsatellite or STR analysis for diagnosis and carrier detection in a DMD family. Two affected patients both demonstrated deletion of exon 51 by multiplex PCR. The microsatellite or STR analysis showed that the mother and all sisters except the eldest sister of the patients carried the disease allelle. Therefore, all of them except the eldest sister were carriers. We present the need to introduce the molecular techniques to improve a mode of diagnosis and management of DMD patients in the Thai community.

Microsatellite instability in Epstein-Barr virus associated with nasopharyngeal carcinoma.

The result reported here represents the first human genomic screen for MSI in Epstein-Barr-Virus associated NPC. The analysis revealed the incidence of MSI only 1 of 23 cases (4%) which indicates that MSI is less common in NPC development.

Extrahepatic biliary atresia in twins: zygosity determination by short tandem repeat loci.

Extrahepatic biliary atresia (EHBA) is an infantile obstructive cholangiopathy of unknown etiology. This condition is generally thought to be an acquired disease without familial tendency. We reported eight pairs of discordant twins in a series of 143 patients with operatively established EHBA, One pair was dizygotic twin from sex discrimination. Six were identical ABO blood groups and 2 were also the same minor blood groups (Dce, MM and Le a-b-). The last 2 sets were monzygotic twins by common DNA polymorphisms short tandem repeat loci. Our findings support the hypothesis that, EHBA is an acquired rather than a hereditary disease.

Multiplex PCR to detect the dystrophin gene deletion in Thai patients.

We have demonstrated the usefulness of the multiplex PCR to directly detect the dystrophin gene mutation. Prenatal diagnosis and confirmation of clinical diagnosis of DMD/BMD via non invasive technique are now possible. Nine DMD and one BMD patients were tested. Five DMD patients demonstrated deletion. Thus, this multiplex PCR could detect deletion in approximately 50 per cent of DMD/BMD Thai patients. Eighty per cent of the deletions were in the distal part, whereas, 20 per cent were in the proximal part. We are planning to establish other molecular techniques such as linkage analysis, cDNA hybridization and immunostaining of dystrophin protein to improve a mode of diagnosis and management of DMD/BMD patients in the Thai community.