Bilirubin - Uridine Diphosphate Glucuronosyltransferase (Ugt1a1) Gene Mutations Among Newborn Babies In The Malay Population In Kelantan With Hyperbilirubinaemia

Sind rom Gilbert berpunca daripada keabnormalan pada gen uridine diphosphate-glucuronosyltransferase 1A 1 (UGT1A 1) yang disebabkan oleh mutasi. Mutasi-mutasi ini berbeza bagi setiap populasi dan kebanyakannya menjadi faktor asas bagi jaundis di kalangan neonat. Objektif kajian ini adalah untuk menentukan frekuensi mutasi-mutasi berikut pada gen UGT1A 1: A(TAh T AA (penyebab yang lazim bagi sind rom Gilbert di kalangan orang-orang Kaukasia), G71 R (penyebab utama pada populasi Jepun dan Taiwan) dan G493R (dijumpai pada wanita Melayu yang membawa mutasi homozigus bagi sind rom Crigler-Najjar jenis ke-2) di kalangan bayi - bayi Melayu di Kelantan yang mengalami hiperbilirubinemia dan juga di kalangan bayi - bayi normal sebagai kawalan serta membandingkan frekuensi mutasi-mutasi ini di antara kedua-dua kumpulan bayi tersebut. Gilbert syndrome is caused by defects in the uridine diphosphateglucuronosyltransferase 1A1 (UGT1A1) gene. These mutations differ among different populations and many of them have been found to be genetic risk factors for the development of neonatal jaundice. The objectives of this study were to determine the frequencies of the following mutations in the UGT1A1 gene: A(TA}yTAA (the most common cause of Gilbert syndrome in Caucasians), G71 R (more common in the Japanese and Taiwanese populations) and G493R (described in a homozygous Malay woman with Crigler-Najjar syndrome type 2) in a group of Malay babies in Kelantan with hyperbilirubinaemia and a group of normal controls and to compare the frequencies of these mutations between these group

Bilirubin-uridine diphosphate glucuronosyltransferase (UGT1A1) gene mutations among newborn babies in the Malay population in Kelantan with hyperbilirubinaemia [RJ276. S961 2005 f rb].

Sindrom Gilbert berpunca daripada keabnormalan pada gen uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) yang disebabkan oleh mutasi. Gilbert syndrome is caused by defects in the uridine diphosphateglucuronosyltransferase 1A1 (UGT1A1) gene

Full-Length Sequence of Mouse Acupuncture-Induced 1-L (Aig1l) Gene Including Its Transcriptional Start Site

We have been investigating the molecular efficacy of electroacupuncture (EA), which is one type of acupuncture therapy. In our previous molecular biological study of acupuncture, we found an EA-induced gene, named acupuncture-induced 1-L (Aig1l), in mouse skeletal muscle. The aims of this study consisted of identification of the full-length cDNA sequence of Aig1l including the transcriptional start site, determination of the tissue distribution of Aig1l and analysis of the effect of EA on Aig1l gene expression. We determined the complete cDNA sequence including the transcriptional start site via cDNA cloning with the cap site hunting method. We then analyzed the tissue distribution of Aig1l by means of northern blot analysis and real-time quantitative polymerase chain reaction. We used the semiquantitative reverse transcriptase-polymerase chain reaction to examine the effect of EA on Aig1l gene expression. Our results showed that the complete cDNA sequence of Aig1l was 6073 bp long, and the putative protein consisted of 962 amino acids. All seven tissues that we analyzed expressed the Aig1l gene. In skeletal muscle, EA induced expression of the Aig1l gene, with high expression observed after 3 hours of EA. Our findings thus suggest that the Aig1l gene may play a key role in the molecular mechanisms of EA efficacy

Herbal Medicine Containing Licorice May Be Contraindicated for a Patient with an HSD11B2 Mutation

Licorice ingestion, as well as mutations in the HSD11B2 gene, inhibits 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) enzyme activity, causing the syndrome of apparent mineral corticoid excess (AME). However, the combined effect of licorice ingestion and an HSD11B2 mutation has never been reported, until now. In this study, we demonstrated that licorice ingestion can produce overt hypertension in an individual without medical history of hypertension who is heterozygous for wild-type and mutant HSD11B2 genes. Our patient was a 51-year-old female with serious hypertension who had been taking herbal medicine containing licorice for more than one year. She was clinically diagnosed as having licorice intoxication, because she did not present with hypertension after ceasing the herbal medicine. Molecular analysis showed that she carried a missense mutation, c.40C>T, in HSD11B2. In conclusion, licorice ingestion is an environmental risk factor for hypertension or AME state in patients with a mutation in HSD11B2. Carrying a mutation in HSD11B2 is, conversely, a genetic risk factor for licorice-induced hypertension or AME state. Herbal medicine containing licorice may, therefore, be contraindicated in patients with an HSD11B2 mutation

A Homozygous Mutation in UGT1A1 Exon 5 May Be Responsible for Persistent Hyperbilirubinemia in a Japanese Girl with Gilbert’s Syndrome

The UGT1A1 gene encodes a responsible enzyme, UDP-glucuronosyltransferase1A1, for bilirubin metabolism. Many mutations have already been identified in patients with inherited disorders with hyperbilirubinemia, Crigler-Najjar syndrome and Gilbert’s syndrome. In this study, we identified a UGT1A1 mutation in an 8-year-old Japanese girl with persistent hyperbilirubinemia who was clinically diagnosed as having Gilbert’s syndrome. For the mutational analysis of UGT1A1, we performed a full sequence analysis of the gene using the patient’s DNA. She was homozygous for a T to G transversion at nucleotide position 1456 in UGT1A1 exon 5 (c.1456T>G), leading to the substitution of aspartate for tyrosine at position 486 of the UGT1A1 protein (p.Y486D). In conclusion, the homozygous mutation of UGT1A1 may be responsible for persistent hyperbilirubinemia in this patient

Adolescent to Adolescent Transformation Program- Nurturing, Enhancing and Promoting Adolescents’ Healthy Habit (ATAP-NEPAH): Curbing Social Problems Among Adolescents in Kelantan Through Peer-To-Peer Health Education

The objectives of ATAP-NEPAH are to enhance and nurture healthy habits among adolescents as well as to empower adolescents in inculcating these healthy habits among them. Health education through peer-to-peer approach is used to instill the knowledge on important areas such as sexual and reproductive health, smoking, substance abuse, illegal street racing (rempit) and mental health. Specific modules were developed by experts (lecturers) in multidisciplinary fields in collaboration with Malaysian Association for Adolescent Health (MAAH), National Population and Family Development Board (NPFDB), Reproductive Health Association of Kelantan (REHAK) and Rhaudatus Sakinah Kelantan. The trained Medical Students Facilitator Team (MSFT) of USM became trainers to secondary one school students. The selected school students were trained by the medical students to become peer educators to their juniors and peers. There was improvement in the readiness level of peer educators, knowledge and attitude towards healthy habits and risky behaviors of other school students after the intervention

The first Malay database toward the ethnic-specific target molecular variation

BACKGROUND:The Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9(th) October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb). FINDINGS:Currently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP ( http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register ). CONCLUSIONS:This database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background

The search for machanism of genetic abberation in the infronic regions of the uridine-diphospate glucuronosyl transferase 1a1 (ugt1a1) gene among neonatal jaundice Malay infants without mutations in the promoter and exonic regions

Many studies have been focusing on the exonic regions of the uridine diphosphate g/ucuronosy/transferase 1 A 1 (UGT1A1) gene in determining the risk factors of neonatal jaundice. However, very few studies suggested the intronic region as a part of it. This study was conducted to determine the possibility of involvement of polymorphisms in the intronic regions among neonatal jaundice Malay infants without polymorphism in the exons. The rationale of this study lwas rely on the other possible risk factors since there were still many infants developed jaundice without exhibit any polymorph isms in the exons of the UGT1A 1 gene. High resolution melting analysis has been used to screen for our target polymorphisms and confirmed by sequencing analysis. A total of 510 (n=260 samples of non-hyperbilirubinemia infants and 250 samples of hyperbilirubinemia infants) were evaluated. This study revealed that from six mutations in the promoter region evaluated,only c.-3279T>G was associated with neonatal jaundice and was statistically significant. Other polymorph isms were detected in the intronic regions such as IVS2+15(T>C) and IVS2+18(C> T) in non· hyperbilirubinemia group while IVS2+82 (C> T) was identified in hyperbilirubinemia group. However, no significanl association Therefore, so far only the c.-3279T>G is a possible risk factor of neonatal jaundice in Malay population

Frequencies of A(TA)7TAA, G71R, and G493R mutations of the UGT1A1 gene in the Malaysian population

The A(TA)7TAA seems more common than the G71R and G493R mutations in the Malaysian population. BACKGROUND: Gilbert syndrome is caused by defects in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene. These mutations differ among different populations and many of them have been found to be genetic risk factors for the development of neonatal jaundice. OBJECTIVES: The objective was to determine the frequencies of the following mutations in the UGT1A1 gene: A(TA)7TAA (the most common cause of Gilbert syndrome in Caucasians), G71R (more common in the Japanese and Taiwanese population), and G493R (described in a homozygous Malay woman with Crigler-Najjar syndrome type 2) in a group of Malaysian babies with hyperbilirubinemia and a group of normal controls. METHODS: The GeneScan fragment analysis was used to detect the A(TA)7TAA variant. Mutation screening of both G71R and G493R was performed using denaturing high performance liquid chromatography. RESULTS: Fourteen out of fifty-five neonates with hyperbilirubinemia (25%) carried the A(TA)7TAA mutation (10 heterozygous, 4 homozygous). Seven out of fifty controls (14%) carried this mutation (6 heterozygous, 1 homozygous). The allelic frequencies for hyperbilirubinemia and control patients were 16 and 8%, respectively (p=0.20). Heterozygosity for the G71R mutation was almost equal among both groups (5.5% for hyperbilirubinemia patients and 6.0% for controls; p=0.61). One subject (1.8%) in the hyperbilirubinemia group and none of the controls were heterozygous for the G493R mutation (p=0.476). CONCLUSIONS: The A(TA)7TAA seems more common than the G71R and G493R mutations in the Malaysian population

Sodium channels of SCNIA gene mutations in generalized epilepsy with febrile seizure plus (GEFS+) spectrum related to autism

Background Mutations in the a-subunit of the first neuronal sodium channel gene SCNIA have been demonstrated for generalized epilepsy \\lith febrile seizures plus (GEFS+), severe myoclonic epilepsy in infancy (SMEI), and borderline SMEI (SMEB). SCNIA mutations are also described in patients 'With psychiatric disorders such as autism. Objective To identify the mutations of SCNIA gene in patients with GEFS+ spectrum which may be related to autism. Methods We examined four patients v.ith autism and GEFS+ spectrum who were admitted to the Department of Child Health, Sardjito Hospital, Yogyakarta, Indonesia. Diagnosis of autism was based on DSMIV;ICD X criteria. Mutations in SCNIA were identified by PCRamplification and denaturing highperformance liquid chromatography analysis, Mth subsequent sequencing. Results There were four patients, all boys, aged 1.8 year to 7 years. The phenotypes of epilepsy were GEFS+ in one patient, SMEB in one patient and SMEI in two patients. Sequencing analysis revealed a GtoA heterozygous transition which was detected at nucleotide c.4834G>A (p.V1612I ) in exon 25. Other single nucleotid polymorphisms (SNPs) were c.383 +66T>C in intron 2, c.603-91G>A and c.603-1060> T in intron 4, c.965-21C> T in intron 6, c.1028+21T>Cin intron 7, c.2173G>A in exon 12 and c. 2177-38C>A, c.2177-12delT, c.2176+44C> T in intron 12. Conclusion In this study, we reported the first cases Mth mutation in SCNIA gene in GEFS+ spectrum related to autistic patients in Indonesian population, which showed a missense mutation p.V16121. [Paediatr lndones. 2010;50:125-32]