Displaying publications 1 - 20 of 124 in total

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  1. Fulltext Risk factors of breast cancer in women in Kelantan, Malaysia
    Afifi M
    Singapore Med J, 2006 Jun;47(6):551; author reply 552-3.
    PMID: 16752028
    Comment on: Norsaʼadah B, Rusli BN, Imran AK, Naing L, Winn T. Risk factors of breast cancer in women in Kelantan, Malaysia. Singapore Med J 2005;
    46:698-705
    Matched MeSH terms: Pedigree
  2. Screening for gap junction protein beta-2 gene mutations in Malays with autosomal recessive, non-syndromic hearing loss, using denaturing high performance liquid chromatography
    Aishah ZS, Khairi MD, Normastura AR, Zafarina Z, Zilfalil BA
    J Laryngol Otol, 2008 Dec;122(12):1284-8.
    PMID: 18353197 DOI: 10.1017/S0022215108002041
    To determine the frequency and type of gap junction protein beta-2 gene mutations in Malay patients with autosomal recessive, non-syndromic hearing loss.
    Matched MeSH terms: Pedigree
  3. Fulltext Comprehensive Genetic Results for Primary Immunodeficiency Disorders in a Highly Consanguineous Population
    Al-Herz W, Chou J, Delmonte OM, Massaad MJ, Bainter W, Castagnoli R, et al.
    Front Immunol, 2018;9:3146.
    PMID: 30697212 DOI: 10.3389/fimmu.2018.03146
    Objective: To present the genetic causes of patients with primary immune deficiencies (PIDs) in Kuwait between 2004 and 2017. Methods: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders Registry. Genomic DNA from patients with clinical and immunological features of PID was sequenced using Sanger sequencing (SS), next generation sequencing (NGS) of targeted genes, whole exome sequencing (WES), and/or whole genome sequencing (WGS). Functional assays were utilized to assess the biologic effect of identified variants. Fluorescence in situ hybridization (FISH) for 22q11.2 deletion and genomic hybridizations arrays were performed when thymic defects were suspected. Results: A total of 264 patients were registered during the study period with predominance of patients with immunodeficiencies affecting cellular and humoral immunity (35.2%), followed by combined immunodeficiencies with associated syndromic features (24%). Parental consanguinity and family history suggestive of PID were reported in 213 (81%) and 145 patients (55%), respectively. Genetic testing of 206 patients resulted in a diagnostic yield of 70%. Mutations were identified in 46 different genes and more than 90% of the reported genetic defects were transmitted by in an autosomal recessive pattern. The majority of the mutations were missense mutations (57%) followed by deletions and frame shift mutations. Five novel disease-causing genes were discovered. Conclusions: Genetic testing should be an integral part in the management of primary immunodeficiency patients. This will help the delivery of precision medicine and facilitate proper genetic counseling. Studying inbred populations using sophisticated diagnostic methods can allow better understanding of the genetics of primary immunodeficiency disorders.
    Matched MeSH terms: Pedigree
  4. Hb lepore/β0-thalassaemia with α+-thalassaemia interactions, a potential diagnostic pitfall
    Alauddin H, Mohamad Nasir S, Ahadon M, Raja Sabudin RZ, Ithnin A, Hussin NH, et al.
    Malays J Pathol, 2015 Dec;37(3):287-92.
    PMID: 26712677
    Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δβ-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/β-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.
    Matched MeSH terms: Pedigree
  5. A case series of α-thalassemia intermedia due to compound heterozygosity for Hb Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] with other α-thalassemias in Malay families
    Alauddin H, Jaapar NA, Azma RZ, Ithnin A, Razak NF, Loh CK, et al.
    Hemoglobin, 2014;38(4):277-81.
    PMID: 24829075 DOI: 10.3109/03630269.2014.916720
    Hb Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a rare hemoglobin (Hb) variant due to a mutation at codon 59 of the α2- or α1-globin gene resulting in a glycine to aspartic acid substitution. Two siblings with a unique coinheritance of Hb Adana and Hb Constant Spring (Hb CS, α142, Term→Gln, TAA>CAA; HBA2: c.427 T>C) (α(codon 59)α/α(CS)α), were compared phenotypically with another two siblings carrying the Hb Adana mutation and a 3.7 kb deletion (α(codon 59)α/-α(3.7)). Although they all had α-thalassemia intermedia (α-TI), the former were clinically more severe than the latter. The first pair of siblings presented at a much younger age than the second pair and showed lower Hb levels and significant extramedullay hemopoiesis. Another case of a hydropic fetus as a result of Hb H/Hb Adana is also described. Their clinical phenotypes and hematological parameters are all presented for comparison.
    Matched MeSH terms: Pedigree
  6. Fulltext Homozygous familial hypercholesterolemia
    Alicezah MK, Razali R, Rahman T, Hoh BP, Suhana NH, Muid S, et al.
    Malays J Pathol, 2014 Aug;36(2):131-7.
    PMID: 25194536 MyJurnal
    We report a rare case of homozygous familial hypercholesterolemia (HoFH), a 22-year-old Malay woman who presented initially with minor soft tissue injury due to a cycling accident. She was then incidentally found to have severe xanthelasma and hypercholesterolemia (serum TC 15.3 mmol/L and LDL-C 13.9 mmol/L). She was referred to the Specialized Lipid Clinic and was diagnosed with familial hypercholesterolemia (FH) based on the Simon Broome (SB) diagnostic criteria. There was a family history of premature coronary heart disease (CHD) in that three siblings had sudden cardiac death, and of consanguineous marriage in that her parents are cousins. DNA screening of LDLR and APOB genes was done by Polymerase Chain Reaction (PCR), followed by Denaturing High Performance Liquid Chromatography (DHPLC). Homozygous mutation C255S in Exon 5 of her LDLR gene was found. There was no mutation was found in Exon 26 and Exon 29 of the APOB gene. This report is to emphasize the importance of identifying patients with FH and cascade screening through established diagnostic criteria and genetic studies in order to ensure early detection and early treatment intervention to minimize the risk of developing CHD and related complications.
    Matched MeSH terms: Pedigree
  7. Fulltext Secondary polycythaemia in a Malay girl with homozygous Hb Tak
    Amran HS, Aziz MA, George E, Mahmud N, Lee TY, Md Noor S
    Malays J Pathol, 2017 Dec;39(3):321-326.
    PMID: 29279598 MyJurnal
    Hb Tak is one of more than 200 high affinity haemoglobin variants reported worldwide. It results from the insertion of two nucleotides (AC) at the termination codon, between codon 146 and codon 147 of the beta-globin gene [Beta 147 (+AC)]. Polycythaemia is the main clinical feature although affected carriers are usually asymptomatic and do not require intervention. Several case studies in this region have reported the co-inheritance of Hb Tak with Hb E, delta beta and beta thalassaemia with one case of homozygous Hb Tak in a Thai boy. In this case report, a cluster of haemoglobin Tak was found in a family of Malay ethnic origin. Cascade family screening was conducted while investigating a 4-year old girl who presented with symptomatic polycythaemia. She had 2 previous Hb analysis done, at 7-month and 2-year-old with the diagnosis of possible Hb Q Thailand and Homozygous Hb D, respectively. Both diagnosis did not fit her clinical presentations. She was plethoric, had reduced exercise tolerance as well as cardiomyopathy. Her parents were consanguineously married and later diagnosed as asymptomatic carriers of Hb Tak. Consequently, re-analysis of the girl's blood sample revealed a homozygous state of Hb Tak. In conclusion, high oxygen affinity haemoglobin like Hb Tak should be considered in the investigation of polycythaemic patients with abnormal Hb analyses. In this case, DNA analysis was crucial in determining the correct diagnosis.
    Matched MeSH terms: Pedigree
  8. Fulltext Neighbouring-group composition and within-group relatedness drive extra-group paternity rate in the European badger (Meles meles)
    Annavi G, Newman C, Dugdale HL, Buesching CD, Sin YW, Burke T, et al.
    J Evol Biol, 2014 Oct;27(10):2191-203.
    PMID: 25234113 DOI: 10.1111/jeb.12473
    Extra-group paternity (EGP) occurs commonly among group-living mammals and plays an important role in mating systems and the dynamics of sexual selection; however, socio-ecological and genetic correlates of EGP have been underexplored. We use 23 years of demographic and genetic data from a high-density European badger (Meles meles) population, to investigate the relationship between the rate of EGP in litters and mate availability, mate incompatibility and mate quality (heterozygosity). Relatedness between within-group assigned mothers and candidate fathers had a negative quadratic effect on EGP, whereas the number of neighbouring-group candidate fathers had a linear positive effect. We detected no effect of mean or maximum heterozygosity of within-group candidate fathers on EGP. Consequently, EGP was associated primarily with mate availability, subject to within-group genetic effects, potentially to mitigate mate incompatibility and inbreeding. In badgers, cryptic female choice, facilitated by superfecundation, superfoetation and delayed implantation, prevents males from monopolizing within-group females. This resonates with a meta-analysis in group-living mammals, which proposed that higher rates of EGP occur when within-group males cannot monopolize within-group females. In contrast to the positive meta-analytic association, however, we found that EGP associated negatively with the number of within-group assigned mothers and the number of within-group candidate fathers; potentially a strategy to counter within-group males committing infanticide. The relationship between the rate of EGP and socio-ecological or genetic factors can therefore be intricate, and the potential for cryptic female choice must be accounted for in comparative studies.
    Matched MeSH terms: Pedigree
  9. Li-Fraumeni syndrome in a Malaysian kindred
    Ariffin H, Martel-Planche G, Daud SS, Ibrahim K, Hainaut P
    Cancer Genet. Cytogenet., 2008 Oct;186(1):49-53.
    PMID: 18786442 DOI: 10.1016/j.cancergencyto.2008.06.004
    We report on a Malaysian kindred with Li-Fraumeni syndrome. The proband was an 8-year-old girl who presented with embryonal rhabdomyosarcoma of the trunk at the age of 8 months and developed a brain recurrence at the age of 7 years, which was 5 years after remission. A younger sister later developed adrenocortical carcinoma at the age of 6 months. Their mother and maternal grandmother were diagnosed with breast cancer at the ages of 26 and 38 years, respectively. TP53 mutation detection in this family revealed a duplication of a GGCGTG motif starting at nucleotide 17579 in exon 10, resulting in an in-frame insertion of two amino acids between residues 334 and 336 in the tetramerization domain of the p53 protein. This mutation was found in the proband and her affected sister as well as her mother. In addition, the mutation was detected in two other siblings (a brother aged 3 years and a sister aged 18 months) who have not yet developed any malignancy. Sequencing of TP53 in the father and two other asymptomatic siblings revealed wild-type TP53. To our knowledge, this is a first report of a Li-Fraumeni syndrome family in Southeast Asia.
    Matched MeSH terms: Pedigree
  10. Fulltext Whole-genome sequencing analysis of phenotypic heterogeneity and anticipation in Li-Fraumeni cancer predisposition syndrome
    Ariffin H, Hainaut P, Puzio-Kuter A, Choong SS, Chan AS, Tolkunov D, et al.
    Proc Natl Acad Sci U S A, 2014 Oct 28;111(43):15497-501.
    PMID: 25313051 DOI: 10.1073/pnas.1417322111
    The Li-Fraumeni syndrome (LFS) and its variant form (LFL) is a familial predisposition to multiple forms of childhood, adolescent, and adult cancers associated with germ-line mutation in the TP53 tumor suppressor gene. Individual disparities in tumor patterns are compounded by acceleration of cancer onset with successive generations. It has been suggested that this apparent anticipation pattern may result from germ-line genomic instability in TP53 mutation carriers, causing increased DNA copy-number variations (CNVs) with successive generations. To address the genetic basis of phenotypic disparities of LFS/LFL, we performed whole-genome sequencing (WGS) of 13 subjects from two generations of an LFS kindred. Neither de novo CNV nor significant difference in total CNV was detected in relation with successive generations or with age at cancer onset. These observations were consistent with an experimental mouse model system showing that trp53 deficiency in the germ line of father or mother did not increase CNV occurrence in the offspring. On the other hand, individual records on 1,771 TP53 mutation carriers from 294 pedigrees were compiled to assess genetic anticipation patterns (International Agency for Research on Cancer TP53 database). No strictly defined anticipation pattern was observed. Rather, in multigeneration families, cancer onset was delayed in older compared with recent generations. These observations support an alternative model for apparent anticipation in which rare variants from noncarrier parents may attenuate constitutive resistance to tumorigenesis in the offspring of TP53 mutation carriers with late cancer onset.
    Matched MeSH terms: Pedigree
  11. Fulltext Two cases of deletion 5p syndrome: one with paternal involvement and another with atypical presentation
    Azman BZ, Akhir SM, Zilfalil BA, Ankathil R
    Singapore Med J, 2008 Apr;49(4):e98-e100.
    PMID: 18418516
    We report two cases of deletion 5p or cri du chat syndrome (CdCS) with different presentations and risks of transmission: one case with paternal chromosome 5 involvement and another, a de novo case with atypical clinical presentation. Cytogenetic analysis was performed on the two cases and their parents. GTG-banded karyotype analysis of Cases 1 and 2 revealed abnormal 46,XY,del(5)(p13-15) male karyotypes. For Case 1, the mother showed normal female karyotype while the father showed an abnormal karyotype involving a balanced translocation 46,XY,t(5;10)(p13;p15). For Case 2, however, both parents showed a normal karyotype pattern. In Case 1, the clinical features, particularly the distinct facial phenotype in combination with a characteristic cat-like cry and hypotonia, aided in the diagnosis at birth and the karyotype analysis was resolutive. The boy in Case 2 presented with atypical clinical features. Even though this patient had multiple syndromic features, the typical high pitched cat-like cry was not prominent. Instead, the patient manifested persistent stridor (from day three of life), which might have prevented the clinician from suspecting CdCS at birth. However, when this patient was presented at seven months of age for cytogenetic analysis, a confirmatory diagnosis of CdCS was established. For children with congenital abnormalities, an early clinical diagnosis confirmed through cytogenetic and molecular investigations, is important for providing personalised diagnostic and prognostic evaluation, and also for genetic counselling on the reproductive risk, particularly for patients with parental chromosome translocation involvement.
    Matched MeSH terms: Pedigree
  12. Fulltext Molecular characterization of two Malaysian patients with Wiskott-Aldrich syndrome
    Baharin MF, Kader Ibrahim SB, Yap SH, Abdul Manaf AM, Mat Ripen A, Dhaliwal JS
    Malays J Pathol, 2015 Aug;37(2):153-8.
    PMID: 26277674 MyJurnal
    The Wiskott-Aldrich Syndrome (WAS) is an X-linked immunodeficiency condition characterized by microthrombocytopenia, eczema and recurrent infections. It is caused by mutations in the Wiskott-Aldrich Syndrome protein (WASP) gene. We investigated two Malay boys who presented with congenital thrombocytopenia, eczema and recurrent infections. Here we report two cases of WASP mutation in Malaysia from two unrelated families. One had a novel missense mutation in exon 1 while the other had a nonsense mutation in exon 2. Both patients succumbed to diseaserelated complications. A differential diagnosis of WAS should be considered in any male child who present with early onset thrombocytopenia, especially when this is associated with eczema and recurrent infections.
    Matched MeSH terms: Pedigree
  13. An unusual mutation in RECQ4 gene leading to Rothmund-Thomson syndrome
    Balraj P, Concannon P, Jamal R, Beghini A, Hoe TS, Khoo AS, et al.
    Mutat Res, 2002 Oct 31;508(1-2):99-105.
    PMID: 12379465
    Rothmund-Thomson syndrome (OMIM #268400) is a severe autosomal recessive genodermatosis: characterised by growth retardation, hyperpigmentation and frequently accompanied by congenital bone defects, brittle hair and hypogonadism. Mutations in helicase RECQ4 gene are responsible for a subset of cases of RTS. Only six mutations have been reported, thus, far and each affecting the coding sequence or the splice junctions. We report the first homozygous mutation in RECQ4 helicase: 2746-2756-delTGGGCTGAGGC in IVS8 responsible for the severe phenotype associated with RTS in a Malaysian pedigree. We report also a 5321 G-->A transition in exon 17 and the updated list of the RECQ4 gene mutations.
    Matched MeSH terms: Pedigree
  14. Toward cultural competence in cancer genetic counseling and genetics education: lessons learned from Chinese-Australians
    Barlow-Stewart K, Yeo SS, Meiser B, Goldstein D, Tucker K, Eisenbruch M
    Genet Med, 2006 Jan;8(1):24-32.
    PMID: 16418596
    PURPOSE: In societies such as Australia with a strong multicultural makeup, culturally determined attitudes to genetics, testing, and counseling may be incompatible with current genetics service provision.

    METHODS: An ethnographic investigation using purposive sampling to increase subject diversity was used to explore the range of beliefs about kinship and inheritance using Chinese-Australians as a case. Participants comprised a sample of 15 Chinese-Australians who had been recruited through several community-based organizations.

    RESULTS: The level of acculturation does not correlate with holding beliefs about inheritance, kinship, and causes of hereditary cancer that are based on "Western" biomedical or traditional concepts. Mismatch between beliefs may exist within families that can impact participation in cancer genetic testing. Family history taking that underpins the surveillance, management, and referral to genetic counseling where there is a strong family history of breast, ovarian, or colorectal cancer can also be impacted unless recognition is made of the patrilineal concept of kinship prevalent in this Chinese-Australian community.

    CONCLUSION: This community-based study confirmed and validated views and beliefs on inheritance and kinship and inherited cancer attributed to senior family members by Chinese-Australians who attended cancer genetic counseling. Barriers to communication can occur where there may be incompatibility within the family between "Western" and traditional beliefs. The findings were used to develop strategies for culturally competent cancer genetic counseling with Australian-Chinese patients. These include nonjudgmental incorporation of their belief systems into the genetic counseling process and avoidance of stereotyping. They have also influenced the development of genetics education materials to optimize family history taking.

    Matched MeSH terms: Pedigree
  15. 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: Pedigree
  16. Genetic Structure and Diversity Among Historic and Modern Populations of the Sumatran Rhinoceros (Dicerorhinus sumatrensis)
    Brandt JR, van Coeverden de Groot PJ, Witt KE, Engelbrektsson PK, Helgen KM, Malhi RS, et al.
    J Hered, 2018 06 27;109(5):553-565.
    PMID: 29684146 DOI: 10.1093/jhered/esy019
    The Sumatran rhinoceros (Dicerorhinus sumatrensis), once widespread across Southeast Asia, now consists of as few as 30 individuals within Sumatra and Borneo. To aid in conservation planning, we sequenced 218 bp of control region mitochondrial (mt) DNA, identifying 17 distinct mitochondrial haplotypes across modern (N = 13) and museum (N = 26) samples. Museum specimens from Laos and Myanmar had divergent mtDNA, consistent with the placement of western mainland rhinos into the distinct subspecies D. s. lasiotis (presumed extinct). Haplotypes from Bornean rhinos were highly diverse, but dissimilar from those of other regions, supporting the distinctiveness of the subspecies D. s. harrissoni. Rhinos from Sumatra and Peninsular Malaysia shared mtDNA haplotypes, consistent with their traditional placement into a single subspecies D. s sumatrensis. Modern samples of D. s. sumatrensis were genotyped at 18 microsatellite loci. Rhinos within Sumatra formed 2 sub-populations, likely separated by the Barisan Mountains, though with only modest genetic differentiation between them. There are so few remaining Sumatran rhinoceros that separate management strategies for subspecies or subpopulations may not be viable, while each surviving rhino pedigree is likely to retain alleles found in no other individuals. Given the low population size and low reproductive potential of Sumatran rhinos, rapid genetic erosion is inevitable, though an under-appreciated concern is the potential for fixation of harmful genetic variants. Both concerns underscore 2 overriding priorities for the species: 1) translocation of wild rhinos to ex situ facilities, and 2) collection and storage of gametes and cell lines from every surviving captive and wild individual.
    Matched MeSH terms: Pedigree
  17. Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells
    Bruce LJ, Wrong O, Toye AM, Young MT, Ogle G, Ismail Z, et al.
    Biochem. J., 2000 Aug 15;350 Pt 1:41-51.
    PMID: 10926824
    We describe three mutations of the red-cell anion exchangerband 3 (AE1, SLC4A1) gene associated with distalrenal tubular acidosis (dRTA) in families from Malaysia and Papua NewGuinea: Gly(701)-->Asp (G701D), Ala(858)-->Asp(A858D) and deletion of Val(850) (DeltaV850). The mutationsA858D and DeltaV850 are novel; all three mutations seem to berestricted to South-East Asian populations. South-East Asianovalocytosis (SAO), resulting from the band 3 deletion of residues400-408, occurred in many of the families but did not itselfresult in dRTA. Compound heterozygotes of each of the dRTA mutationswith SAO all had dRTA, evidence of haemolytic anaemia and abnormal red-cell properties. The A858D mutation showed dominant inheritance and therecessive DeltaV850 and G701D mutations showed a pseudo-dominantphenotype when the transport-inactive SAO allele was also present. Red-cell and Xenopus oocyte expression studies showed that theDeltaV850 and A858D mutant proteins have greatly decreased aniontransport when present as compound heterozygotes (DeltaV850/A858D,DeltaV850/SAO or A858D/SAO). Red cells with A858D/SAO had only 3% ofthe SO(4)(2-) efflux of normal cells, thelowest anion transport activity so far reported for human red cells. The results suggest dRTA might arise by a different mechanism for eachmutation. We confirm that the G701D mutant protein has an absoluterequirement for glycophorin A for movement to the cell surface. Wesuggest that the dominant A858D mutant protein is possibly mis-targetedto an inappropriate plasma membrane domain in the renal tubular cell,and that the recessive DeltaV850 mutation might give dRTA because ofits decreased anion transport activity.
    Matched MeSH terms: Pedigree
  18. Fulltext The use of the amplification refractory mutation system (arms) in the detection of rare beta-thalassemia mutations in the Malays and Chinese in Malaysia
    Chan YF, Tan KL, Wong YC, Wee YC, Yap SF, Tan JAMA
    Southeast Asian J. Trop. Med. Public Health, 2001 Dec;32(4):872-9.
    PMID: 12041567
    Molecular characterization and prenatal diagnosis for beta-thalassemia can be carried out using the Amplification Refractory Mutation System (ARMS). The ARMS is a rapid and direct molecular technique in which beta-thalassemia mutations are visualized immediately after DNA amplification by gel electrophoresis. In the University of Malaya Medical Center, molecular characterization and prenatal diagnosis for beta-thalassemia is carried out using ARMS for about 96% of the Chinese and 84.6% of the Malay patients. The remaining 4% and 15.4% of the uncharacterized mutations in the Chinese and Malay patients respectively are detected using DNA sequencing. DNA sequencing is an accurate technique but it is more time-consuming and expensive compared with the ARMS. The ARMS for the rare Chinese beta-mutations at position -29 (A-->G) and the ATG-->AGG base substitution at the initiator codon for translation in the beta-gene was developed. In the Malays, ARMS was optimized for the beta-mutations at codon 8/9 (+G), Cap (+1) (A-->C) and the AATAAA-->AATAGA base substitution in the polyadenylation region of the beta-gene. The ARMS protocols were developed by optimization of the parameters for DNA amplification to ensure sensitivity, specificity and reproducibility. ARMS primers (sequences and concentration), magnesium chloride concentration, Taq DNA polymerase and PCR cycling parameters were optimized for the specific amplification of each rare beta-thalassemia mutation. The newly-developed ARMS for the 5 rare beta-thalassemia mutations in the Chinese and Malays in Malaysia will allow for more rapid and cost-effective molecular characterization and prenatal diagnosis for beta-thalassemia in Malaysia.
    Matched MeSH terms: Pedigree
  19. Whole exome sequencing identifies a novel SCN1A mutation in genetic (idiopathic) generalized epilepsy and juvenile myoclonic epilepsy subtypes
    Chan CK, Low JS, Lim KS, Low SK, Tan CT, Ng CC
    Neurol Sci, 2020 Mar;41(3):591-598.
    PMID: 31720899 DOI: 10.1007/s10072-019-04122-9
    INTRODUCTION: Genetic (idiopathic) generalized epilepsy (GGE) is a common form of epilepsy characterized by unknown aetiology and a presence of genetic component in its predisposition.

    METHODS: To understand the genetic factor in a family with GGE, we performed whole exome sequencing (WES) on a trio of a juvenile myoclonic epilepsy/febrile seizure (JME/FS) proband with JME/FS mother and healthy father. Sanger sequencing was carried out for validation of WES results and variant detection in other family members.

    RESULTS: Predictably damaging variant found in affected proband and mother but absent in healthy father in SCN1A gene was found to be associated with generalized epilepsy and febrile seizure. The novel non-synonymous substitution (c.5753C>T, p.S1918F) in SCN1A was found in all family members with GGE, of which 4/8 were JME subtypes, and/or febrile seizure, while 3 healthy family member controls did not have the mutation. This mutation was also absent in 41 GGE patients and 414 healthy Malaysian Chinese controls.

    CONCLUSION: The mutation is likely to affect interaction between the sodium channel and calmodulin and subsequently interrupt calmodulin-dependent modulation of the channel.

    Matched MeSH terms: Pedigree
  20. Fulltext A novel Bruton's tyrosine kinase gene (BTK) invariant splice site mutation in a Malaysian family with X-linked agammaglobulinemia
    Chear CT, Gill HK, Ramly NH, Dhaliwal JS, Bujang N, Ripen AM, et al.
    Asian Pac J Allergy Immunol, 2013 Dec;31(4):320-4.
    PMID: 24383975 DOI: 10.12932/AP0304.31.4.2013
    X-linked agammaglobulinemia (XLA) is a rare genetic disorder caused by mutations in the Bruton's tyrosine kinase (BTK) gene. These mutations cause defects in early B cell development. A patient with no circulating B cells and low serum immunoglobulin isotypes was studied as were his mother and sister. Monocyte BTK protein expression was evaluated by flow cytometry. The mutation was determined using PCR and followed by sequencing. Flow cytometry showed the patient lacked BTK protein expression in his monocytes while the mother and sister had 62% and 40% of the monocytes showing BTK protein expressions respectively. The patient had a novel base substitution in the first nucleotide of intron 9 in the BTK gene, and the mutation was IVS9+1G
    Matched MeSH terms: Pedigree
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