Displaying publications 41 - 60 of 117 in total

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  1. Novel mutations in SKIV2L and TTC37 genes in Malaysian children with trichohepatoenteric syndrome
    Lee WS, Teo KM, Ng RT, Chong SY, Kee BP, Chua KH
    Gene, 2016 Jul 15;586(1):1-6.
    PMID: 27050310 DOI: 10.1016/j.gene.2016.03.049
    Trichohepatoenteric syndrome (THES) is a rare autosomal recessive disorder that is classically associated with intractable diarrhea with an onset within the first few months of life. Herein, we investigated and reported novel mutations in two causal genes in 3 Malaysian cases. Genomic DNA was extracted from peripheral blood obtained from patients in two Malaysian Chinese families. The exons of SKIV2L and TTC37 genes were amplified and sequenced by bi-directional sequencing to identify the point mutations within the coding sequence. Three Chinese boys from two families with characteristic features and clinical course were diagnosed with THES. In family-1, two point mutations were identified in the SKIV2L gene (c.1891G>A and c.3187C>T). In family-2, a single-nucleotide duplication (c.3426dupA) was found in the TTC37 gene. These mutations cause the production of abnormal non-functional gene product leading to the clinical manifestations in the patients. We reported three point mutations, which have not been previously described in other patients with THES in SKIV2L and TTC37 genes, including one nonsense, one frameshift, and one missense mutations.
    Matched MeSH terms: Exons
  2. Towards understanding pre-mRNA splicing mechanisms and the role of SR proteins
    Sahebi M, Hanafi MM, van Wijnen AJ, Azizi P, Abiri R, Ashkani S, et al.
    Gene, 2016 Aug 10;587(2):107-19.
    PMID: 27154819 DOI: 10.1016/j.gene.2016.04.057
    Alternative pre-mRNA splicing provides a source of vast protein diversity by removing non-coding sequences (introns) and accurately linking different exonic regions in the correct reading frame. The regulation of alternative splicing is essential for various cellular functions in both pathological and physiological conditions. In eukaryotic cells, this process is commonly used to increase proteomic diversity and to control gene expression either co- or post-transcriptionally. Alternative splicing occurs within a megadalton-sized, multi-component machine consisting of RNA and proteins; during the splicing process, this complex undergoes dynamic changes via RNA-RNA, protein-protein and RNA-protein interactions. Co-transcriptional splicing functionally integrates the transcriptional machinery, thereby enabling the two processes to influence one another, whereas post-transcriptional splicing facilitates the coupling of RNA splicing with post-splicing events. This review addresses the structural aspects of spliceosomes and the mechanistic implications of their stepwise assembly on the regulation of pre-mRNA splicing. Moreover, the role of phosphorylation-based, signal-induced changes in the regulation of the splicing process is demonstrated.
    Matched MeSH terms: Exons
  3. Compound heterozygous mutations in TTC7A cause familial multiple intestinal atresias and severe combined immunodeficiency
    Yang W, Lee PP, Thong MK, Ramanujam TM, Shanmugam A, Koh MT, et al.
    Clin Genet, 2015 Dec;88(6):542-9.
    PMID: 25534311 DOI: 10.1111/cge.12553
    Familial multiple intestinal atresias is an autosomal recessive disease with or without combined immunodeficiency. In the last year, several reports have described mutations in the gene TTC7A as causal to the disease in different populations. However, exact correlation between different genotypes and various phenotypes are not clear. In this study, we report identification of novel compound heterozygous mutations in TTC7A gene in a Malay girl with familial multiple intestinal atresias and severe combined immunodeficiency (MIA-SCID) by whole exome sequencing. We found two mutations in TTC7A: one that destroyed a putative splicing acceptor at the junction of intron 17/exon 18 and one that introduced a stop codon that would truncate the last two amino acids of the encoded protein. Reviewing the recent reports on TTC7A mutations reveals correlation between the position and nature of the mutations with patient survival and clinical manifestations. Examination of public databases also suggests carrier status for healthy individuals, making a case for population screening on this gene, especially in populations with suspected frequent founder mutations.
    Matched MeSH terms: Exons
  4. Fulltext Blau Syndrome Associated with Nucleotide-binding Oligomerization Domain Containing 2 Mutation in a Baby from Malaysia
    Leong KF, Sato R, Oh GGK, Surana U, Pramono ZAD
    Indian J Dermatol, 2019 9 24;64(5):400-403.
    PMID: 31543536 DOI: 10.4103/ijd.IJD_44_18
    Blau syndrome (BS) is a very rare autosomal dominant juvenile inflammatory disorder caused by mutation in nucleotide-binding oligomerization domain containing 2 (NOD2). Usually, dermatitis is the first symptom that appears in the 1st year of life. About 220 BS cases with confirmed NOD2 mutation have been reported. However, the rarity and lack of awareness of the disease, especially in the regions where genetic tests are very limited, often result in late diagnosis and misdiagnosis. Here, we report a de novo BS case from Malaysia, which may be the first report from southeast Asia. PCR and DNA sequencing of peripheral blood mononuclear cells were performed to screen the entire coding region of NOD2 gene. A heterozygous c.1000C>T transition in exon 4, p. R334W, of the NOD2 gene was identified in the patient. This report further reaffirms the ubiquitousness of the disease and recurrency of p. R334W mutation.
    Matched MeSH terms: Exons
  5. Fulltext The presence of single-nucleotide polymorphisms in Hps4 gene in a subset of schizophrenic patients in Pahang: a preliminary study
    Norafiza Zainuddin, Maizatul Akma Mamat, Norlelawati A. Talib
    International Journal of Allied Health Sciences, 2017;1(2):14-27.
    MyJurnal
    Schizophrenia is a devastating mental disorder that affects people’s normal life with heterogeneous features of its clinical presentation, as well as its molecular attribute. In order to identify the potential molecular aberration, particularly single nucleotide polymorphism (SNP) which could be important in the aetiology of schizophrenia, polymerase chain reaction (PCR)-DNA sequencing approach was utilized for targeting the exon (and intron) 9 of the Hermansky-Pudlak syndrome type 4 (HPS4) gene. DNAs were extracted from peripheral blood of nine schizophrenic patients and one normal individual prior to PCR-DNA sequencing. Following DNA sequencing, a SNP (A>G) which is rs713998 at nucleotide position 22618 of exon 9 of the HPS4 gene was observed in eight schizophrenia samples. Moreover, DNA sequencing results also revealed an intronic aberration/SNP which is rs3747129 (C>T) at nucleotide position 22789 of intron 9 of the HPS4 gene in four schizophrenia samples. A SNP which is rs739289 (G>T) at nucleotide position 22677 of the intron was also found in eight schizophrenia samples. The importance of both the exonic and intronic aberrations is yet to be confirmed with further research involving larger population and other relevant clinical parameters. That notwithstanding, these preliminary results suggested that single nucleotide aberrations, particularly SNPs might have a role in the development of schizophrenia
    Matched MeSH terms: Exons
  6. Fulltext MLH1 and MSH2 gene mutations and polymorphisms in six Malay families with hereditary nonpolyposis colorectal cancer
    Wan Khairunnisa Wan Juhari, Khairul Bariah Ahmad Amin Noordin, Wan Faiziah Wan Abdul Rahman, Andee Dzulkarnaen Zakaria, Ahmad Shanwani Mohd Sidek, Muhammad Radzi Abu Hassan, et al.
    International Medical Journal Malaysia, 2018;17(1):71-78.
    MyJurnal
    Background: Hereditary nonpolyposis colorectal cancer (HNPCC) also known as Lynch syndrome is commonly caused by genetic alterations in any of the four mismatch repair (MMR) genes; MLH1, MSH2, MSH6 and PMS2. This is the first study aimed to investigate genetic variants in Malay HNPCC families. Methods: Six Malay HNPCC families who fulfilled any of the Bethesda criteria were recruited into this study. A total of 3 ml of blood was withdrawn from each patient in the families. The samples were further analyzed using polymerase chain reaction and direct sequencing of the selected exons of MLH1 and MSH2 genes. Results: Two missense mutations and four single nucleotide polymorphisms (SNPs) were identified in six patients. These variants in the MLH1 and MSH2 genes were identified in four families who met the revised Bethesda guidelines. In two families, no mutation and polymorphism was identified in both the exon and intron of the respective genes. Of the mutations and polymorphisms identified, five have never been reported in Malay HNPCC families before. A missense mutation was detected in exon 5 of the MLH1 gene, c.394G>C (p.Asp132His) and four mutations and polymorphisms were detected in the MSH2 gene; heterozygous c.211+98T>C and c.211+9C>G and homozygous c.211+98T>C and c.211+9C>G, c.367-86A>C and c.382C>G. Conclusion: The results represented a new spectrum of mutations and polymorphisms in the Malay HNPCC families. However, a larger study involving additional families and analysis is required to determine the impact and nature of the identified mutations and polymorphisms.
    Matched MeSH terms: Exons
  7. Fulltext TG-SK, a teak (Tectona grandis Linn.) homolog of GSK-3/ shaggy protein kinase
    Norlia B., Norwati M., Norwati A., Mohd Rosli H., Norihan M. S.
    Buletin Persatuan Genetik Malaysia, 2006;12(1):7-8.
    MyJurnal
    This study was part of the larger studies to isolate and characterize gene related to flowering in teak. This study isolated differentially expressed genes of teak flowering tissues. One of the genes encodes plant protein kinases highly homologous to the AtSK-II of Arabidopsis GSK3/SHAGGY subfamily. The gene was named as Tectona grandis SHAGGY kinase (Tg-SK). The protein sequence of this gene contained the characteristic catalytic domain of GSK-3/SHAGGY protein kinase. The gene also shows the same genomic organization of 11 introns and 12 exons. Although the size of the introns varies, the positions of exon/intron boundaries are very similar to AtSK-II. The discovery of this gene in teak, which is a forest tree species, supports the hypothesis, which suggested the gene is found in all eukaryotes.
    Matched MeSH terms: Exons
  8. Fulltext Detection of CYP2C19 Genetic Variants in Malaysian Orang Asli from Massively Parallel Sequencing Data
    Ang GY, Yu CY, Subramaniam V, Abdul Khalid MI, Tuan Abdu Aziz TA, Johari James R, et al.
    PLoS One, 2016;11(10):e0164169.
    PMID: 27798644 DOI: 10.1371/journal.pone.0164169
    The human cytochrome P450 (CYP) is a superfamily of enzymes that have been a focus in research for decades due to their prominent role in drug metabolism. CYP2C is one of the major subfamilies which metabolize more than 10% of all clinically used drugs. In the context of CYP2C19, several key genetic variations that alter the enzyme's activity have been identified and catalogued in the CYP allele nomenclature database. In this study, we investigated the presence of well-established variants as well as novel polymorphisms in the CYP2C19 gene of 62 Orang Asli from the Peninsular Malaysia. A total of 449 genetic variants were detected including 70 novel polymorphisms; 417 SNPs were located in introns, 23 in upstream, 7 in exons, and 2 in downstream regions. Five alleles and seven genotypes were inferred based on the polymorphisms that were found. Null alleles that were observed include CYP2C19*3 (6.5%), *2 (5.7%) and *35 (2.4%) whereas allele with increased function *17 was detected at a frequency of 4.8%. The normal metabolizer genotype was the most predominant (66.1%), followed by intermediate metabolizer (19.4%), rapid metabolizer (9.7%) and poor metabolizer (4.8%) genotypes. Findings from this study provide further insights into the CYP2C19 genetic profile of the Orang Asli as previously unreported variant alleles were detected through the use of massively parallel sequencing technology platform. The systematic and comprehensive analysis of CYP2C19 will allow uncharacterized variants that are present in the Orang Asli to be included in the genotyping panel in the future.
    Matched MeSH terms: Exons
  9. Rare homozygous disease-associated sequence variants in children with spinal muscular atrophy: a phenotypic description and review of the literature
    Li L, Menezes MP, Smith M, Forbes R, Züchner S, Burgess A, et al.
    Neuromuscul Disord, 2024 Apr;37:29-35.
    PMID: 38520993 DOI: 10.1016/j.nmd.2024.03.005
    5q-associated spinal muscular atrophy (SMA) is the most common autosomal recessive neurological disease. Depletion in functional SMN protein leads to dysfunction and irreversible degeneration of the motor neurons. Over 95 % of individuals with SMA have homozygous exon 7 deletions in the SMN1 gene. Most of the remaining 4-5 % are compound heterozygous for deletion and a disease-associated sequence variant in the non-deleted allele. Individuals with SMA due to bi-allelic SMN1 sequence variants have rarely been reported. Data regarding their clinical phenotype, disease progression, outcome and treatment response are sparse. This study describes six individuals from three families, all with homozygous sequence variants in SMN1, and four of whom received treatment with disease-modifying therapies. We also describe the challenges faced during the diagnostic process and intrafamilial phenotypic variability observed between siblings.
    Matched MeSH terms: Exons
  10. Gefitinib as first line therapy in Malaysian patients with EGFR mutation-positive non-small-cell lung cancer: A single-center retrospective study
    Abdullah MM, Bhat A, Mohamed AK, Ching FY, Ahmed N, Gantotti S
    Oncol Lett, 2016 Apr;11(4):2757-2762.
    PMID: 27073548
    The present retrospective, single-center study evaluated the objective response rate (ORR) and progression-free survival (PFS) of epidermal growth factor receptor (EGFR) mutation-positive Malaysian patients with advanced lung adenocarcinoma treated with gefitinib. During May 2008 to July 2013, 33 patients with Stage IV, EGFR mutation-positive non-small-cell lung cancer (NSCLC) were identified and received gefitinib (250 mg) as first line treatment. The primary and secondary end points were ORR, PFS and safety, respectively. A total of 18 (54.5%) and 2 (6.1%) patients achieved partial response (PR) and complete response (CR) to gefitinib therapy, respectively, yielding an ORR of 60.6% (95% CI, 42.1-77.1%). Patients with exon 20 or 21 mutations (n=6, 66.7%) tended to have better ORR compared with exon 19 (n=22, 59.1%). The median PFS was 8.9 months in Malaysian patients with EGFR mutation-positive NSCLC, treated with gefitinib. The majority of treatment-related toxicity was mild in nature. The most frequently reported adverse events included dry skin (39.4%), skin rash (27.2%), and dermatitis acneiform (15.2%). In conclusion, Malaysian patients with locally advanced and metastatic EGFR mutation-positive NSCLC responded favorably to gefitinib therapy in terms of ORR, median PFS, and tolerability, the results of which were consistent with those of the IPASS study conducted in an Asian population. Considering the efficacy and safety profile of gefitinib, it is a favorable option for the first-line treatment of Malaysian patients with EGFR mutation-positive NSCLC. However, future long-term studies in a larger population of Malaysian patients are required to support whether the prolonged PFS conferred by gefitinib will translate into prolonged overall survival.
    Matched MeSH terms: Exons
  11. Genetic study of early-onset Parkinson's disease in the Malaysian population
    Tay YW, Tan AH, Lim JL, Lohmann K, Ibrahim KA, Abdul Aziz Z, et al.
    Parkinsonism Relat Disord, 2023 Jun;111:105399.
    PMID: 37209484 DOI: 10.1016/j.parkreldis.2023.105399
    BACKGROUND: About 5-10% of Parkinson's disease (PD) cases are early onset (EOPD), with several genes implicated, including GBA1, PRKN, PINK1, and SNCA. The spectrum and frequency of mutations vary across populations and globally diverse studies are crucial to comprehensively understand the genetic architecture of PD. The ancestral diversity of Southeast Asians offers opportunities to uncover a rich PD genetics landscape, and identify common regional mutations and new pathogenic variants.

    OBJECTIVES: This study aimed to investigate the genetic architecture of EOPD in a multi-ethnic Malaysian cohort.

    METHODS: 161 index patients with PD onset ≤50 years were recruited from multiple centers across Malaysia. A two-step approach to genetic testing was used, combining a next-generation sequencing-based PD gene panel and multiplex ligation-dependent probe amplification (MLPA).

    RESULTS: Thirty-five patients (21.7%) carried pathogenic or likely pathogenic variants involving (in decreasing order of frequency): GBA1, PRKN, PINK1, DJ-1, LRRK2, and ATP13A2. Pathogenic/likely pathogenic variants in GBA1 were identified in thirteen patients (8.1%), and were also commonly found in PRKN and PINK1 (11/161 = 6.8% and 6/161 = 3.7%, respectively). The overall detection rate was even higher in those with familial history (48.5%) or age of diagnosis ≤40 years (34.8%). PRKN exon 7 deletion and the PINK1 p.Leu347Pro variant appear to be common among Malay patients. Many novel variants were found across the PD-related genes.

    CONCLUSIONS: This study provides novel insights into the genetic architecture of EOPD in Southeast Asians, expands the genetic spectrum in PD-related genes, and highlights the importance of diversifying PD genetic research to include under-represented populations.

    Matched MeSH terms: Exons
  12. Phospholipase A2 group v in benign familial fleck retina in a set of triplets
    Bin NJ, Heng HM, Poh R, Noor SM, Subrayan V
    Retina, 2015 Jun;35(6):1266-72.
    PMID: 25549071 DOI: 10.1097/IAE.0000000000000446
    To evaluate the association of phospholipase A2, Group V (PLA2G5), with benign familial fleck retina in a consanguineous family with triplets.
    Matched MeSH terms: Exons/genetics
  13. Fulltext Two novel tyrosinase (TYR) gene mutations with pathogenic impact on oculocutaneous albinism type 1 (OCA1)
    Ghodsinejad Kalahroudi V, Kamalidehghan B, Arasteh Kani A, Aryani O, Tondar M, Ahmadipour F, et al.
    PLoS One, 2014;9(9):e106656.
    PMID: 25216246 DOI: 10.1371/journal.pone.0106656
    Oculocutaneous albinism (OCA) is a heterogeneous group of autosomal recessive disorders resulting from mutations of the tyrosinase (TYR) gene and presents with either complete or partial absence of pigment in the skin, hair and eyes due to a defect in an enzyme involved in the production of melanin. In this study, mutations in the TYR gene of 30 unrelated Iranian OCA1 patients and 100 healthy individuals were examined using PCR-sequencing. Additionally, in order to predict the possible effects of new mutations on the structure and function of tyrosinase, these mutations were analyzed by SIFT, PolyPhen and I-Mutant 2 software. Here, two new pathogenic p.C89S and p.H180R mutations were detected in two OCA1 patients. Moreover, the R402Q and S192Y variants, which are common non-pathogenic polymorphisms, were detected in 17.5% and 35% of the patients, respectively. The outcome of this study has extended the genotypic spectrum of OCA1 patients, which paves the way for more efficient carrier detection and genetic counseling.
    Matched MeSH terms: Exons/genetics
  14. Fulltext Prevalence of PALB2 mutations in breast cancer patients in multi-ethnic Asian population in Malaysia and Singapore
    Phuah SY, Lee SY, Kang P, Kang IN, Yoon SY, Thong MK, et al.
    PLoS One, 2013;8(8):e73638.
    PMID: 23977390 DOI: 10.1371/journal.pone.0073638
    The partner and localizer of breast cancer 2 (PALB2) is responsible for facilitating BRCA2-mediated DNA repair by serving as a bridging molecule, acting as the physical and functional link between the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risks of developing breast cancer in various populations.
    Matched MeSH terms: Exons/genetics
  15. International evaluation of unrecognizably uglifying human faces in late and severe secondary hyperparathyroidism in chronic kidney disease. Sagliker syndrome. A unique catastrophic entity, cytogenetic studies for chromosomal abnormalities, calcium-sensing receptor gene and GNAS1 mutations. Striking and promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4
    Yildiz I, Sagliker Y, Demirhan O, Tunc E, Inandiklioglu N, Tasdemir D, et al.
    J Ren Nutr, 2012 Jan;22(1):157-61.
    PMID: 22200434 DOI: 10.1053/j.jrn.2011.10.030
    Hypotheses explaining pathogenesis of secondary hyperparathyroidism (SH) in late and severe CKD as a unique entity called Sagliker syndrome (SS) are still unclear. This international study contains 60 patients from Turkey, India, Malaysia, China, Romania, Egypt, Tunisia, Taiwan, Mexico, Algeria, Poland, Russia, and Iran. We examined patients and first degree relatives for cytogenetic chromosomal abnormalities, calcium sensing receptor (Ca SR) genes in exons 2 and 3 abnormalities and GNAS1 genes mutations in exons 1, 4, 5, 7, 10, 13. Our syndrome could be a new syndrome in between SH, CKD, and hereditary bone dystrophies. We could not find chromosomal abnormalities in cytogenetics and on Ca SR gene exons 2 and 3. Interestingly, we did find promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4. We finally thought that those catastrophic bone diseases were severe SH and its late treatments due to monetary deficiencies and iatrogenic mistreatments not started as early as possible. This was a sine qua non humanity task. Those brand new striking GNAS1 genes missense mutations have to be considered from now on for the genesis of SS.
    Matched MeSH terms: Exons/genetics
  16. Founder mutation in the BRCA1 gene in Malay breast cancer patients from Singapore
    Lee AS, Ho GH, Oh PC, Balram C, Ooi LL, Lim DT, et al.
    Hum Mutat, 2003 Aug;22(2):178.
    PMID: 12872263
    The mutation spectrum of the BRCA1 gene among ethnic groups from Asia has not been well studied. We investigated the frequency of mutations in the BRCA1 gene among Malay breast cancer patients from Singapore, independent of family history. By using the protein truncation test (PTT) and direct sequencing, BRCA1 mutations were detected in 6 of 49 (12.2%) unrelated patients. Four novel missense mutations in exon 11, T557A (1788A>G), T582A (1863A>G), N656S (2086A>G) and P684S (2169C>T) were identified in one patient. Two patients had missense mutations in exon 23, V1809A (5545T>C), which has been previously detected in individuals from Central and Eastern Europe. Three unrelated patients had the deleterious 2846insA frameshift mutation in exon 11. Methylation specific PCR (MSP) of the promoter region of the BRCA1 gene detected hypermethylation of tumor DNA in an additional 2 patients. Haplotype analysis using the microsatellite markers D17S855, D17S1323 and D17S1325 revealed a common haplotype for the three unrelated patients and their three relatives with the 2846insA mutation. These findings strongly suggest that the 2846insA mutation, the most common deleterious mutation in this study, may possibly be a founder mutation in breast cancer patients of Malay ethnic background.
    Matched MeSH terms: Exons/genetics
  17. Fulltext De Novo Truncating Variants in the Last Exon of SEMA6B Cause Progressive Myoclonic Epilepsy
    Hamanaka K, Imagawa E, Koshimizu E, Miyatake S, Tohyama J, Yamagata T, et al.
    Am J Hum Genet, 2020 04 02;106(4):549-558.
    PMID: 32169168 DOI: 10.1016/j.ajhg.2020.02.011
    De novo variants (DNVs) cause many genetic diseases. When DNVs are examined in the whole coding regions of genes in next-generation sequencing analyses, pathogenic DNVs often cluster in a specific region. One such region is the last exon and the last 50 bp of the penultimate exon, where truncating DNVs cause escape from nonsense-mediated mRNA decay [NMD(-) region]. Such variants can have dominant-negative or gain-of-function effects. Here, we first developed a resource of rates of truncating DNVs in NMD(-) regions under the null model of DNVs. Utilizing this resource, we performed enrichment analysis of truncating DNVs in NMD(-) regions in 346 developmental and epileptic encephalopathy (DEE) trios. We observed statistically significant enrichment of truncating DNVs in semaphorin 6B (SEMA6B) (p value: 2.8 × 10-8; exome-wide threshold: 2.5 × 10-6). The initial analysis of the 346 individuals and additional screening of 1,406 and 4,293 independent individuals affected by DEE and developmental disorders collectively identified four truncating DNVs in the SEMA6B NMD(-) region in five individuals who came from unrelated families (p value: 1.9 × 10-13) and consistently showed progressive myoclonic epilepsy. RNA analysis of lymphoblastoid cells established from an affected individual showed that the mutant allele escaped NMD, indicating stable production of the truncated protein. Importantly, heterozygous truncating variants in the NMD(+) region of SEMA6B are observed in general populations, and SEMA6B is most likely loss-of-function tolerant. Zebrafish expressing truncating variants in the NMD(-) region of SEMA6B orthologs displayed defective development of brain neurons and enhanced pentylenetetrazole-induced seizure behavior. In summary, we show that truncating DNVs in the final exon of SEMA6B cause progressive myoclonic epilepsy.
    Matched MeSH terms: Exons/genetics*
  18. Amelogenesis imperfecta: enamel ultra structure and molecular studies
    Gopinath VK, Al-Salihi KA, Yean CY, Ann MC, Ravichandran M
    J Clin Pediatr Dent, 2004;28(4):319-22.
    PMID: 15366620
    Amelogenesis imperfecta (AI) is a hereditary disorder resulting in generalized defects in the enamel. The case reported here is of a seven-year-old male child with yellow color of all his teeth. Two of his primary molars were extracted due to dental abscess with advanced root resorption. Histologically hypoplastic enamel layer, positively birefringent, generalized pitting, roughness with irregular general cracked borders were observed. Scanning electron microscope, revealed extensive irregular, disorganized rough superficial enamel layer. The enamel was irregularly decussate with filamentous prisms accompanied by small rounded formations. The morphological and histological examination of the tooth revealed that this patient has the features of AI. For genetic study blood sample were collected from the patient and PCR analysis revealed that there is no mutation in exons 1-7 of AMELX gene on the X chromosome of the patient. Hence, it is probable that the AI of this patient is not X-linked. It is more likely to be an autosomal mutation.
    Matched MeSH terms: Exons/genetics
  19. Fulltext The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity
    Colombo M, Lòpez-Perolio I, Meeks HD, Caleca L, Parsons MT, Li H, et al.
    Hum Mutat, 2018 May;39(5):729-741.
    PMID: 29460995 DOI: 10.1002/humu.23411
    Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR (dPCR), the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele of approximately 20%. The posterior probability of pathogenicity was 7.44 × 10-115 . There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24) nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the nonpathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants.
    Matched MeSH terms: Exons/genetics
  20. The 172-kb genomic DNA region of the O. rufipogon yld1.1 locus: comparative sequence analysis with O. sativa ssp. japonica and O. sativa ssp. indica
    Song BK, Hein I, Druka A, Waugh R, Marshall D, Nadarajah K, et al.
    Funct Integr Genomics, 2009 Feb;9(1):97-108.
    PMID: 18633654 DOI: 10.1007/s10142-008-0091-x
    Common wild rice (Oryza rufipogon) plays an important role by contributing to modern rice breeding. In this paper, we report the sequence and analysis of a 172-kb genomic DNA region of wild rice around the RM5 locus, which is associated with the yield QTL yld1.1. Comparative sequence analysis between orthologous RM5 regions from Oryza sativa ssp. japonica, O. sativa ssp. indica and O. rufipogon revealed a high level of conserved synteny in the content, homology, structure, orientation, and physical distance of all 14 predicted genes. Twelve of the putative genes were supported by matches to proteins with known function, whereas two were predicted by homology to rice and other plant expressed sequence tags or complementary DNAs. The remarkably high level of conservation found in coding, intronic and intergenic regions may indicate high evolutionary selection on the RM5 region. Although our analysis has not defined which gene(s) determine the yld1.1 phenotype, allelic variation and the insertion of transposable elements, among other nucleotide changes, represent potential variation responsible for the yield QTL. However, as suggested previously, two putative receptor-like protein kinase genes remain the key suspects for yld1.1.
    Matched MeSH terms: Exons/genetics
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