PubMed Health⌕ Search

Biomedical subjects

Chanin Limwongse

Publications and source records attributed to Chanin Limwongse.

15 recordsLinked to original sources
PubMed2006

A newly recognized polyosteolysis/hyperostosis syndrome.

We report a newly recognized bone disorder consisting of polyostotic expansile osteolysis affecting long bones and iliac bones; hyperostosis of the skull, thoracic cage, and medial portion of both clavicles; pectus carinatum; gigantiform synovial masses of the elbows and knees; atrial septal defect; cardiomegaly; unilateral cryptorchidism; and mental deficiency. Affected bones can be grouped into four general types of skeletal pathology: (1) expansile osteolysis, (2) osteolysis without expansion, (3) expansion without osteolysis, and (4) hyperostosis. Some bones remained unaffected. We have named the condition "polyosteolysis/hyperostosis syndrome." It is clearly at variance with any previously reported bone disorder, including familial expansile osteolysis, juvenile Paget disease, and McCune-Albright syndrome (and polyostotic fibrous dysplasia). Because our patient shared some features in common with juvenile Paget disease, we thought that mutational analysis of TNFRSF11B was indicated, even though our patient had some manifestations not found in juvenile Paget disease. Direct sequencing failed to identify a TNFRSF11B mutation. Because the parents of our propositus were first cousins suggests that polyosteolysis/hyperostosis syndrome may possibly have autosomal recessive inheritance.

Child↗
PubMed2006

Contiguous gene syndrome of holoprosencephaly and hypotrichosis simplex: association with an 18p11.3 deletion.

We report a patient with a unique combination of features, including microcephaly; mental retardation; poorly developed frontal lobes; hypoplastic pituitary gland; hypothyroidism; alopecia universalis; single maxillary central incisor; taurodontism; median palatal ridge; longitudinally grooved nails; and scoliosis. His unbalanced karyotype was found to be 45,XY,der(15;18)(q10;q10). The constellation of anomalies appears to represent a contiguous gene syndrome caused, at least in part, by deletion of TGIF and the gene responsible for hereditary hypotrichosis simplex. The phenotype of our patient differs other reported patients with del(18p). Possible explanations include (1) the effects of a different deleted region, (2) a positional effect caused by a gene close by, or (3) by interruption of a different gene resulting from chromosomal translocation.

Abnormalities, Multiple↗
PubMed2006

Mutations of AML1 in non-M0 acute myeloid leukemia: six novel mutations and a high incidence of cooperative events in a South-east Asian population.

Point mutations of AML1 are uncommon and predominantly reported in a rare minimally differentiated acute myeloid leukemia (M0 AML). Few data exist regarding the frequency of AML1 mutations in non-M0 cases. We screened 284 consecutive adult Thai patients with de novo AML and found that 3.9% had AML1 mutations. The highest incidence occurred in M6. Six novel mutations were uniquely identified in non-M0 cases. Sixty-four percent of the non-M0 patients with AML1 mutations had coexisting genetic abnormalities including FLT3 mutation in 36%. Our study provides evidence to support the model of multiple co-operating events, which could also be critical in the development of leukemia in non-M0 AML patients with mutated AML1. The prognostic significance of these novel mutations remains to be determined.

Acute Disease↗
PubMed2006

Mutation analysis of the GNE gene in distal myopathy with rimmed vacuoles (DMRV) patients in Thailand.

Distal myopathy with rimmed vacuoles (DMRV) is an early-adult-onset, distal myopathy caused by a mutation of the UDP-N-acetylglucosamine 2 epimerase/N-acetylmannosamine kinase (GNE) gene. We herein report four Thai patients with DMRV who carried compound heterozygous mutations of the GNE gene including three novel (p.G89R, p.P511T, and p.I656N) and two known mutations (p.A524V and p.V696M). All patients shared p.V696M in one allele. Our study demonstrates the mutation spectrum of the GNE gene in Thai patients with DMRV.

Adult↗
PubMed2006

Novel and de-novo truncating PAX6 mutations and ocular phenotypes in Thai aniridia patients.

PURPOSE: To describe the ophthalmic findings and mutation analyses of the PAX6 gene in Thai aniridia patients. METHODS: Ten patients from six unrelated families underwent a comprehensive ophthalmic examination. Mutations in the PAX6 gene were screened by single-strand conformational polymorphism (SSCP) and direct DNA sequencing of the SSCP variants. RESULTS: Seven patients developed cataracts and six developed glaucoma. Mutation analysis demonstrated four different truncating mutations, two of which were de novo. These included one novel insertion/deletion mutation (c.474del12insGA in exon 5) and three nonsense mutations. R203X and R240X are common recurrent mutations, while Q277X in exon 10 is novel. All mutations resulted in loss of function of the PAX6 protein. CONCLUSION: Our data confirm inter- and intrafamilial variable phenotypic manifestations of which the underlying mechanisms may be haploinsufficiency or dominant-negative mutation.

Adolescent↗
PubMed2006

Floppy infant caused by MTM1 mutation: a first genetically-confirmed X-linked myotubular myopathy patient in Thailand.

Floppy infant syndrome (FIS) refers to a condition wherein an infant manifests generalized hypotonia since birth or in early life. It is heterogeneous and can be caused by various central nervous system disorders, neuromuscular diseases and genetic disorders. X-linked myotubular myopathy (XMTM) is a progressive congenital myopathy morphologically characterized by the presence of centrally placed nuclei in numerous muscle fibers without any other particular pathological abnormalities. Patients are frequently born with floppiness and respiratory distress. The vast majority of patients carry a truncating or missense mutation in MTM1. The authors report here a full term male baby with clinicopathological features of XMTM. The diagnosis is validated by the finding of a c. 141-144delAGAA mutation ofMTM1. To the best of the authors' knowledge, the present case is the first genetically confirmed XMTM in Thailand. A brief review of various neuromuscular disorders causing floppy infant syndrome is also included.

Chromosome Mapping↗
PubMed2006

Real-time three dimensional sonographic features of an early third trimester fetus with achondrogenesis.

Generalized shortening of fetal long bones detected from prenatal sonographic examination usually raise a tentative diagnosis of skeletal dysplasia. Information obtained from grey-scale scan is frequently not sufficient to provide a definite diagnosis, and the images are not readily comprehensible for the parents-to-be. Lately, three-dimensional sonography has become increasing available in obstetric practice. The authors report here a rare case of fetal achondrogenesis, which is a lethal form of skeletal dysplasia, in a 30-week-old fetus using real-time three-dimensional ultrasound. The prenatal findings of fetal achondrogenesis from this technique were thoroughly described, along with postnatal radiography and autopsy results. Sonographic features from this imaging technique allow for an accurate diagnosis and better understanding of the parents. This facilitates the genetic counseling process, as well as the parental options for further care.

Achondroplasia↗
PubMed2005

Mutations of the FLT3 gene in adult acute myeloid leukemia: determination of incidence and identification of a novel mutation in a Thai population.

FLT3 mutations have been reported to be the most frequent mutation in acute myeloid leukemia (AML). No data currently exist regarding FLT3 mutations in Southeast Asian patients. In this study, the incidence and type of FLT3 mutation in a large series of Thai AML patients were determined. FLT3 internal tandem duplication (ITD) mutations were observed in 24.6%, FLT3 tyrosine kinase domain mutations in 3.1%, and dual mutations in 2.7% of 256 newly diagnosed Thai AML patients. ITD mutations were mostly restricted to the juxtamembrane domain, and the in-frame ITD length varied from 21 to 201 base pairs. Six types of point mutations were identified, including Asp835Tyr, Asp835His, Asp835Glu, Asp835Ala, Ile836, and a novel mutation, Asp835Del/Ile836Val, which resulted in the loss of aspartic acid and substitution of isoleucine by valine. A rare leukemia karyotype, trisomy 11, was found to coexist with this novel FLT3 mutation, whereas the majority of patients with FLT3 mutations had a normal karyotype. Overall, FLT3 mutation was associated with a significantly higher white blood cell count and older age than the wild-type FLT3. In conclusion, the incidence of FLT3 mutation in Thailand is as high as that of western countries. The clinical significance of the novel mutation requires further studies in a larger population.

Acute Disease↗
PubMed2005

A Thai family with hereditary pancreatitis and increased cancer risk due to a mutation in PRSS1 gene.

AIM: To investigate mutation of serine protease 1-cationic trypsinogen (CT, PRSS1) gene in members of a Thai family with hereditary pancreatitis and pancreatic cancer. METHODS: Polymerase chain reaction and direct sequencing were performed to analyze the PRSS1 gene in two members of the family affected by pancreatitis. Allele specific amplification (ASA) method was then developed to detect the mutation of the PRSS1 gene in all available members of the family and normal control subjects. RESULTS: A cytosine (C) to thymine (T) mutation at position 2441 (g.2441C>T) of the PRSS1 gene, which results in a substitution of arginine by cysteine at position 116 (R116C) of CT, was identified by direct sequencing in both clinically affected members of the family but was not found in the unaffected member. This mutation, which might be arising from deamination of methylated cytosine in CpG dinucleotide of codon 116 (CGT>TGT), was also detected by the ASA method in the two affected members and a proband's brother but was not observed in unaffected members and 54 normal control subjects. CONCLUSION: Autosomal dominant pancreatitis with increased cancer risk in the studied Thai family is most likely due to missense (R116C) mutation in the PRSS1 gene.

Exons↗
PubMed2005

Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome presenting with a large nephrogenic cyst, severe oligohydramnios and hydrops fetalis: a case report and review of the literature.

OBJECTIVES: To report a case of EEC syndrome with a large nephrogenic cyst detected by prenatal ultrasonography. METHODS: Prenatal ultrasonographic detection, genetic counselling, termination of pregnancy, radiographic study, autopsy and ultrastructural study of scalp hair. The literature on EEC syndrome with genitourinary anomalies and prenatal diagnosis was also reviewed. RESULTS: A 6-cm cyst in the right side of abdominal cavity was detected in a fetus of 24 weeks' gestational age with severe oligohydramnios and hydrops fetalis. The autopsy revealed bilateral renal dysplasia with a large nephrogenic cyst at the right side and markedly hypoplastic urinary bladder and pulmonary hypoplasia. The fetus also had ectrodactyly and syndactyly of hands and feet and ectodermal dysplasia and left cleft lip and palate. Ultrastructure of hair from scanning electron microscopy revealed no obvious abnormality. CONCLUSION: This is a rare case of fetal malformation partly detected prenatally. In order to detect this syndrome, careful ultrasound search for acral anomalies should be performed in cases with renal malformation or obstructive uropathy.

Abnormalities, Multiple↗
PubMed2004

Novel and de novo PKD1 mutations identified by multiple restriction fragment-single strand conformation polymorphism (MRF-SSCP).

BACKGROUND: We have previously developed a long RT-PCR method for selective amplification of full-length PKD1 transcripts (13.6 kb) and a long-range PCR for amplification in the reiterated region (18 kb) covering exons 14 and 34 of the PKD1 gene. These have provided us with an opportunity to study PKD1 mutations especially in its reiterated region which is difficult to examine. In this report, we have further developed the method of multiple restriction fragment-single strand conformation polymorphism (MRF-SSCP) for analysis of PKD1 mutations in the patients with autosomal dominant polycystic kidney disease (ADPKD). Novel and de novo PKD1 mutations are identified and reported. METHODS: Full-length PKD1 cDNA isolated from the patients with ADPKD was fractionated into nine overlapping segments by nested-PCR. Each segment was digested with sets of combined restriction endonucleases before the SSCP analysis. The fragments with aberrant migration were mapped, isolated, and sequenced. The presence of mutation was confirmed by the long-range genomic DNA amplification in the PKD1 region, sequencing, direct mutation detection, and segregation analysis in the affected family. RESULTS: Five PKD1 mutations identified are two frameshift mutations caused by two di-nucleotide (c. 5225_5226delAG and c.9451_9452delAT) deletions, a nonsense (Q1828X, c.5693C>T) mutation, a splicing defect attributable to 31 nucleotide deletion (g.33184_33214del31), and an in-frame deletion (L3287del, c.10070_10072delCTC). All mutations occurred within the reiterated region of the gene involving exons 15, 26, 15, 19 and 29, respectively. Three mutations (one frameshift, splicing defect, and in-frame deletion) are novel and two (one frameshift and nonsense) known. In addition, two mutations (nonsense and splicing defect) are possibly de novo. CONCLUSION: The MRF-SSCP method has been developed to analyze PCR products generated by the long RT-PCR and nested-PCR technique for screening PKD1 mutations in the full-length cDNA. Five mutations identified were all in the reiterated region of this gene, three of which were novel. The presence of de novo PKD1 mutations indicates that this gene is prone to mutations.

Codon, Nonsense↗
PubMed2004

Hemoglobin Pakse: presence on red blood cell membrane and detection by polymerase chain reaction-single-strand conformational polymorphism.

Nondeletional gene mutations giving rise to alpha-thalassemia can be found at polymorphic frequency in Southeast Asia. Although the most common is hemoglobin Constant Spring (Hb CS), caused by a termination codon mutation (UAA --> CAA, Gln) in the alpha2-globin gene and resulting in reduced synthesis of the elongated alpha-globin variant, Hb Pakse (UAA --> UAU, Tyr) also has been observed at a significant prevalence. Western blot analysis of ghost membrane proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis from an individual with alpha-thal 1/Hb Pakse revealed the existence of a higher molecular weight globin of 18 kd consistent with an alpha(Pakse)-globin chain. The presence of alpha(Pakse)-globin on membranes of Hb Pakse-containing red blood cells affords an explanation for the severity of anemia observed in such patients. However, because the 2 Hb variants cannot be distinguished by current biochemical techniques, we developed a convenient single-tube polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) protocol for the simultaneous diagnosis of Hb CS and Hb Pakse by amplifying a short fragment covering the termination codon of the alpha2-globin gene. This PCR-SSCP method required no internal control coamplification or use of restriction enzymes and has the potential of identifying all the other possible termination codon mutations in a single reaction with only 1 pair of primers.

Codon↗
PubMed2003

A new syndrome of symphalangism, multiple frenula, postaxial polydactyly, dysplastic ears, dental anomalies, and exclusion of NOG and GDF5.

A Thai girl with a unique combination of limb and craniofacial anomalies is reported. Manifestations include blepharoptosis; prominent nose; hypodontia; multiple, hyperplastic frenula; and dysplastic ears. Limb anomalies include short stature, postaxial polydactyly of both hands and the left foot, proximal and distal symphalangism of fingers, and congenital absence of the distal phalanges of toes 2-5. Mutation analyses of NOG and GDF5, the genes responsible for symphalangism-related syndromes, were negative.

Bone Morphogenetic Proteins↗
PubMed2003

Ultrasonographic prenatal diagnosis of Treacher Collins syndrome: a case report.

A case of Treacher Collins syndrome (TCS) diagnosed prenatally using ultrasonography is reported. The pregnant woman was gravida 2, para 0. Her husband had stigmata of the syndrome. Ultrasonography revealed polyhydramnios, abnormal fetal ears and marked micrognathia. Abortion occurred spontaneously at 26 weeks of gestation. The abortus bore clinical features of the syndrome.

Abortion, Spontaneous↗