Sultana MH Faradz
Division Of Human Genetics, Center For Biomedical Research, Faculty Of Medicine Diponegoro University

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Hair root FMRP expression for screening of fragile X full mutation females Rujito, Lantip; Kustiani, Dwi; Severijnen, Lies Anne; Hanzon, Peter; Faradz, Sultana MH; Willemsen, Rob
Universa Medicina Vol 30, No 1 (2011)
Publisher : Faculty of Medicine, Trisakti University

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2011.v30.11-21

Abstract

The fragile X syndrome is the most common form of inherited mental retardation in humans, caused by an expansion of the cytosine-guanine-guanine (CGG) repeat in the fragile X mental retardation 1 (FMR1) gene located on the X chromosome. Antibody tests have been developed to identify fragile X patients, based on the presence or absence of fragile mental retardation protein (FMRP) in both lymphocytes and hair roots. The objective of this study was to compare correlations of hair root and lymphocyte FMRP expression with cognitive functioning in female rural area probands carrying the full mutation. Thirty females (normal, premutation, or full mutation) were selected from Indonesian fragile X families and were tested for FMRP expression in lymphocytes and hair roots using the FMRP antibody test. Subject genotype was determined by Southern blot analysis, and IQ equivalent by Raven’s Standard Progressive Matrices. Statistical analysis was by Pearson correlation. FMRP expression in blood lymphocytes was relatively higher than that in hair roots, but hair root FMRP expression was strongly correlated with cognitive functioning in female full mutation carriers (r=0.64, p=0.015), whereas no significant correlation between lymphocyte FMRP and cognitive functioning was found (r=0.31, p= 0.281). Around 14% of subjects had a normal and 7% a borderline IQ level, while 79% had mild mental impairment. In conclusion, hair root FMRP expression may be a useful marker for identification of fragile X full mutation females.
Sikap Orang Tua Terhadap Penerimaan Konseling Genetika Pada Down Syndrome W, Costrie G.; Faradz, Sultana MH; K, Niken Safitri Dyan
Jurnal Keperawatan Anak Vol 2, No 1 (2014): Jurnal Keperawatan Anak
Publisher : Jurnal Keperawatan Anak

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Abstract

Background: Genetics counseling can improve individual knowledge and decrease the level of anxiety. More information about genetic diseases received by individu will make them more comfortable because of the certainty. However, the low of public awareness and understanding of issues concerning the genetic disease resulted in the unrecognized the existence of genetic counseling. Research on how attitudes towards genetic counseling in families with Down syndrome child are felt necessary. This study aims to determine parents’ attitudes towards receiving genetic counseling of Down syndrome. Methods: A quantitative approach used questionnaire was applied cross-sectionally to parents of child with Down syndrome in one special school Semarang. Sample was determined by purposive sampling. Univariate and bivariate analysis were performed to analyze data. Results: A total of 51 respondents participated in this study. The results showed that the majority of respondents (84.3%) supported a genetic counseling session on Down syndrome. Most of the respondents (98.0%) had a positive attitude toward a child with Down syndrome. Based on the bivariate analysis, there was no significant difference (p-value = 0.416) between father and mother attitudes toward receiving genetic counseling of Down syndrome. Conclusion: Most of the respondents were interested in genetic counseling session although they did not know about it previously.
ANALISIS GEN GSTM1 NULL, GSTT1 NULL, RASIO GSH/GSSG DAN KADAR LOGAM BERAT TERHADAP DERAJAT AUTISM SPEKTRUM DISORDER Hermawati, Donna; A, Mahayu Dewi; Utari, Agustini; Winarni, Tri Indah; Faradz, Sultana MH
JNH (Journal of Nutrition and Health) Vol 7, No 2 (2019): JNH (JOURNAL OF NUTRITION AND HEALTH)
Publisher : Universitas Diponegoro

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (473.941 KB) | DOI: 10.14710/jnh.7.2.2019.1-10

Abstract

Background : Autism Spectrum Disorder (ASD) is an behavioral disorder included in multifactorial disease. Several theory said that genetics factor, parental age, immunologic dysfunction, chemical induced, heavy metal intoxication and oxidative stress are related to ASD. A study about genetics and environmental factor is very important. High polymorphism of GSTM1 and GSTT1 genes were reported in autism population. The measurement of heavy metal concentration in hair specimen has been done to know excretion ability of the body. GSTM1 null and GSTT1 null polymorphism in subjects with autism, reflect individual vulnerability for environmental induced, such as heavy metal. Objectives : The objectives of this study was to know the frequency of GSTM1 null and GSTT 1null od ASD patients compare to the wildtype and the heavy metal concentration (Pb and Hg) of ASD patients Methods: Blood samples and hair specimen were collected from thirty eight autism children of Autism School in Semarang, Surakarta and Probolinggo. The Multiplex Polymerase Chain Reaction was used to analyze GSTM1 and GSTT1 gene. The GSH and GSSG concentration were done using ELISA. Heavy metal (Pb) concentration of hair specimen were done using  Atomic Absorption Spectrophotometer. Results : The higher frequency of GSTM1 null & GSTT1 null were obtained in ASD children compared to the wildtype. The average of  Pb concentration reached beyond the maximum standart (3,34 ppm).
STRATEGI COPING ORANGTUA YANG MEMPUNYAI ANAK DENGAN DISORDERS OF SEX DEVELOPMENT KROMOSOM SEKS MOSAIK Fitrianingrum, Iit; Ediati, Annastasia; Faradz, Sultana MH
Jurnal Psikologi Vol 17, No 2 (2018): Oktober 2018
Publisher : Faculty of Psychology, Diponegoro University

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (634.374 KB) | DOI: 10.14710/jp.17.2.189-203

Abstract

This study aims to explore coping strategies used by parents’ of children with mosaic sex chromosome Disorders of Sex Development (DSD). The study applied the sequential explanatory mixed-methods approach that collected quantitative data prior to qualitative data.  Participants were parents of the affected patients diagnosed with DSD with the following karyotype XX/XY, X/XY, XYY, or XXY variants. In total, 14 mothers and 12 fathers of 14 patients with a mosaic sex chromosome DSD participated in this study. We used the Indonesian version of BRIEF COPE to collect quantitative data on coping strategies. Furthermore, an invidual interview was conducted to all participants to elaborate the coping strategies applied by parents in raising their children. The data analysis identified the four most preferred parental coping strategies:  religion, positive reframing, acceptance, and active coping whereas the least preferred coping strategies were humor, substance use, and behavior disengagement. Mothers and fathers in the study did not significantly differ in applying their coping strategies (p>.05). The study suggests health practitioners working with parents of patients affected with mosaic sex chromosome DSD to promote the religion, positive reframing, acceptance, and active coping strategies to facilitate a better acceptance of the affected children.
PHENOTYPE-GENOTYPE AND PEDIGREE ANALYSIS OF ISOLATED HYPOSPADIAS PATIENTS Vikawati, Nura Eky; Santosa, Ardy; Juniarto, Achmad Zulfa; Faradz, Sultana MH
Indonesian Journal of Urology Vol 25 No 1 (2018)
Publisher : Indonesian Urological Association

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32421/juri.v25i1.390

Abstract

Objective: Hypospadias is a malformation in urethra which has many range of severity. A patient with Isolated hypospadias (IH), a mild disorder of sex development (DSD) has a hypospadias phenotype only. Hypospadias is considered as multifactorial disease in which genetic factors contribute to its development. Chromosome analysis in DSD including hypospadias is conducted for gender assignment and other possible genetic contributions. This analysis solely could not elucidate all genetic causes of hypospadias. Polymorphism of V89L in SRD5A2 is suggested as one of genetic risk factors of hypospadias. To determine the genetic risk factor and pattern of inheritance, a good pedigree construction is required. Material & methods: 35 eligible subjects with IH admitted to Center for Biomedical Research (CEBIOR) during 2012-2015 were randomly selected. 35 normal male as control were included in this study. Data on three generation pedigrees were collected from medical records in 35 affected subjects. Chromosome analyses were done by using G-banding technique. Polymorphism analysis of V89L in SRD5A2 gene was done using PCR-RFLP technique in all samples. Results: From the 35 affected subjects, the most frequent phenotype was penile hypospadias (47%), a pair of twins were monozygotic and one had a cousin diagnosed with urogenital abnormalities (i.e micropenis and chordae). All subjects had 46,XY chromosome. No chromosomal aberration was found. No positive correlation between polymorphism of V89L in SRD5A2 and risk of hypospadias (PR of CC+CG vs GG=1.0, 95% CI: 0.342−2.921, p value=1.0). Conclusion: The pedigree data from our study implies tendency of genetic involvement in hypospadias cases. There were no chromosomal aberrations in hypospadias cases. The finding on polymorphism of V89L in SRD5A2 gene does not support that of previous studies.
Are GSTM1 Null and GSTT1 Null Risk Factor of Autism Spectrum Disorder? A Preliminary Study Donna Hermawati; Sue-Mian Then; Tri Indah Winarni; Rahman Jamal; Sultana MH Faradz
MEDIA MEDIKA INDONESIANA 2012:MMI VOLUME 46 ISSUE 2 YEAR 2012
Publisher : MEDIA MEDIKA INDONESIANA

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Abstract

Background: Low plasma total glutathione (tGSH) levels, elevated levels of oxidized glutathione (GSSG) and low ratios of tGSH to GSSG in autism were reported. Glutathione S-transferases (GST) are antioxidant enzymes that play important role in cellular detoxification and the excretion of environmental pollutants including heavy metals. Glutathione S-transferase mu (GSTM1) and Glutathione S-transferase theta (GSTT1) are known to be highly polymorphic. Homozygous deletions of these genes result in lack ofenzyme activity and impaired the ability to excrete metals including mercury. Combined effects of mercury (Hg) accumulation coupled with decreased levels of antioxidants (low glutathione and antioxidant enzymes) contribute to the phenotypic presentation of autism spectrum disorder (ASD). Association of GSTM1 null genotype with autism has been reported. Therefore the preliminary study was performed to investigate the role of GSTM1 null and GSTT1 null as risk factor of ASD associated with phenotype expression.Method: Fifty one ASD patients were recruited from special need & autism school and 45 controls from Semarang & Solo. Blood veins samples were collected and genomic DNA was extracted by salting-out method in CEBIOR Semarang. Genotyping for GSTM1 and GSTT1 gene was done in UMBI Malaysia. Multiplex PCR was performed and PCR products were separated on 1.2 % agarose gel, stained with ethidium bromide and visualized on UV transiluminator. GSTM1 & GSTT1 gene product is about 625 bp and 459 bp. Absence of GSTM1 and GSTT1 gene band was interpreted as GSTM1 null & GSTT1 null.Results: The frequency of GSTM1 null and GSTT1 null in ASD higher compared with control group but the difference is not statistically significant (p=0.357, OR=0.504; 95% CI 0.117-2.168 and p=0.364, OR=0.674; 95% CI 0.287-1.580). There is also no statistically different in the distribution of GSTM1 null and GSTT1 null between mild to moderately autistic and severely autistic (p=0.983, OR=0.980; 95% CI 0.158-6.095 and p=0.439, OR=1.633; 95% CI 0.471-5.656).Conclusion: GSTM1 null and GSTT1 null are not risk factor of ASD. Further investigations are needed with a bigger sample size, analyzing multiple GST genes and GST activity determination to find out the gene susceptibility of ASD and factors that contribute to the phenotype expression of ASD.Keywords: GSTM1 null, GSTT1 null, risk factor, autism spectrum disorder ABSTRAKApakah GSTM1 Null dan GSTT1 Null merupakan faktor risiko autism spectrum disorder? Studi pendahuluanLatar belakang: Pada autism ditemukan bahwa glutathion total plasma (tGSH) rendah, oxidized glutathione (GSSG) meningkat dan rasio tGSH terhadap GSSG rendah. Glutathione s-transferase (GST) merupakan enzim antioksidan yang berperan penting dalam proses detoksifikasi seluler dan ekskresi polutan lingkungan termasuk diantaranya logam berat. Polimorfisme gen GST mu (GSTM1) dan GST theta (GSTT1) cukup tinggi. Delesi homozigot gen GSTM1 dan GSTT1 yang menyebabkan berkurang sampai tidak adanya aktivitas enzim GST serta menurunnya level antioksidan berkontribusi terhadap risiko ASD. Oleh karena itu dilakukan penelitian pendahuluan untuk mengetahui hubungan antara gen GSTM1 null dan GSTT1 null sebagai faktor risiko ASD dengan ekspresi fenotip.Metode: Lima puluh satu pasien ASD dari SLB dan sekolah autis serta 45 kontrol dari Semarang dan Solo diambil darah vena, kemudian diekstraksi dengan metode salting-out diCEBIOR Semarang. Pemeriksaan genotip gen GSTM1 & GSTT1 dilakukan di UMBI Malaysia. Metode yang digunakan adalah PCR multipleks, setelah itu produk PCR dipisahkanpada 1,2% gel agarosa kemudian dicat dengan ethidium bromida dan hasilnya dilihat menggunakan transiluminator UV. Besar produk untuk GSTM1 & GSTT1 adalah 625 bp &459 bp. Tidak adanya band untuk gen GSTM1 & GSTT1 diinterpretasikan sebagai GSTM1 null & GSTT1 null.Hasil: Frekuensi gen GSTM1 null dan GSTT1 null pada ASD lebih tinggi dibandingkan kontrol tetapi tidak ditemukan perbedaan yang signifikan (p=0,357, OR=0,504; 95% CI0,117-2,168 and p=0,364, OR=0,674; 95% CI 0,287-1,580). Distribusi gen GSTM1 null dan GSTT1 null pada autis ringan sedang dan autis berat juga tidak ditemukan perbedaan yang signifikan secara statistik (p=0,983, OR=0,980; 95% CI 0,158-6,095 and p=0,439, OR=1,633; 95% CI 0,471-5,656).Simpulan: GSTM1 null dan GSTT1 null bukan merupakan faktor risiko ASD. Penelitian lebih lanjut sangat diperlukan dengan jumlah sampel yang lebih besar, analisis gen GSTmultipel dan pemeriksaan aktivitas GST untuk mendapatkan gen faktor risiko ASD dan faktor-faktor yang mempengaruhi ekspresi fenotip ASD.
The Role of SHOX Gene in Short Stature of Turner Syndrome and Its Variant Tri Indah Winarni; Farmaditya EP Mundhofir; Sultana MH Faradz
MEDIA MEDIKA INDONESIANA 2010:MMI VOLUME 44 ISSUE 2 YEAR 2010
Publisher : MEDIA MEDIKA INDONESIANA

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Abstract

Background: SHOX gene is located on the edge of each short/p arm sex chromosome called the pseudoautosomal region-1 (PAR1) plays as a fundamental role on controlling chondrocyte differentiation and apoptosis in the growth plate. Longitudinal growth is determined by environmental, hormonal and genetic factors. Short stature is defined as a standing height below the third percentile according to Tanner et al. Short stature affects approximately 2% of children. Turner syndrome is the most common genetic disorder in female characterized by the absence of all or part of a normal second X chromosome, affecting 1:2500 live-born female babies. Short stature and ovarian failure is the main clinical feature. The objective of this study is to elucidate the implication of SHOX gene in short stature of Turner Syndrome and its variant.Method: Purposive sampling was performed to recruit female with short stature after informed consent agreement. Female with growth treatment history and chronic diseases was excluded from this study. Cytogenetics testing was done for all samples by G-banding method, in routine karyotyping. Result: We report 9 females with short stature which cytogenetically and clinically diagnosed as Turner Syndrome. Four cases is classic Turner syndrome with standing height is below third percentile, three cases are 45,X/46,X,i(Xq) with standing height is below third percentile, one case is 46,XX/45,X (80%) with standing height is below third percentile, and the rest is 46,XX/45,X (20%) with standing height is between 3rd–97th percentile or normal.Conclusion: SHOX gene haploinsufficiency is strongly indicated the cause of short stature in Turner Syndrome.ABSTRAKPeran gen SHOX pada perawakan pendek Sindrom Turner dan variannyaLatar belakang: Gen SHOX terdapat di ujung lengan pendek kromosom seks yang disebut pseudoautosomal regio-1 (PAR1) yang berperan penting pada pengaturan diferensiasi kondrosit and apoptosis di lempeng epifisis. Pertumbuhan memanjang ditentukan oleh faktor lingkungan, hormon, dan faktor genetik. Menurut Tanner dkk, perawakan pendek didefinisikan sebagai tinggi badan kurang dari tiga persentil dan diperkirakan terjadi pada 2% populasi anak-anak. Sindrom Turner merupakan kelainan genetik pada perempuan yang paling banyak ditemukan akibat hilangnya sebagian atau seluruh kromosom X normal yang kedua dengan gambaran klinik utama berupa short stature dan insufisiensi ovarium, dengan insidensi 1:2500 bayi lahir hidup. Tujuan penelitian ini untuk memahami peran gen SHOX pada perawakan pendek Sindrom Turner dan variannya.Metode: Subjek penelitian adalah wanita berperawakan pendek yang setuju mengikuti penelitian dengan menandatangani informed consent. Dilakukan eksklusi untuk wanita berperawakan pendek dengan riwayat pengobatan pemacu pertumbuhan dan penyakit kronik. Pemeriksaan sitogenetik dengan metode pengecatan Giemsa dilakukan pada semua preparat kromosom dilanjutkan dengan analisis kromosom rutin.Hasil: Dilaporkan sembilan (9) wanita berperawakan pendek yang secara sitogenetik dan klinis didiagnosis sebagai Sindrom Turner. Empat kasus didiagnosis sebagai Sindrom Turner klasik dengan tinggi badan di bawah tiga persentil, tiga kasus dengan 45,X/46,X,i(Xq) dengan tinggi badan di bawah tiga persentil, satu kasus dengan 46,XX/45,X (80%) dengan tinggi badan di bawah tiga persentil, dan sisanya adalah 46,XX/45,X (20%) dengan tinggi badan di bawah antara 3-97 persentil atau normal.Simpulan: Haploinsufficiency gen SHOX diduga kuat menyebabkan perawakan pendek pada Sindrom Turner.
Cytogenetic Analysis for Research and Services Sultana MH Faradz
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016): SUPPLEMENT
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (13.131 KB) | DOI: 10.19106/JMedScieSup004804201631

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AbstractThat the correct chromosome number in man is 46 was first recognized by Tjio and Levan in 1956. Perhaps few Indonesians know that Tjio was an Indonesian scientist studying in Sweden and then living in the US. Cytogenetic analyses are commonly performed to determine both structural and numerical chromosome aberration, whilst changes in chromosomes can lead to birth defects, syndromes, or even cancer.  Several chromosomal aneuploidy syndromes were identified after the establishment of various chromosome banding techniques in late 1960’s.  Specific cell culture media was found to express fragile site in the beginning of 1970’s and since then, inherited Fragile X Mental Retardation syndrome could be diagnosed.  However, some female permutation cases have been often misdiagnosed. Further molecular analysis has resolved this problem by revealing more CGG repeats in the promoter region FMR1 gene, which is related to the expression of fragile site and the severity of the diseases.In Disorder of Sex Development (DSD), early gender assignment and reconstruction surgery has been challenged because of the dilemma of gender identity development in later life. Cytogenetic analysis for the first-line gender assignment is important in newborn with DSD. Proper diagnosis with hormonal and mutation analysis should be elucidated to avoid medical, psychological, and social aspect in adult life. The most frequent genetic cases in our clinical experiences have been Androgen Insensitivity Syndrome and Congenital Adrenal Hyperplasia. Female Complete Androgen Insensitivity Syndrome (CAIS) with main symptom primary amenorrhea without cytogenetic analysis has often been diagnosed as inguinal hernia because of testicle location and size.Diagnosis and treatment of several leukemias and lymphomas, as well as some solid tumors, depend on cytogenetic analyses to demonstrate consistent, specific chromosomal aberrations. Chromosome analysis in hematologic malignancy is indicated to support diagnosis, select therapy regimen, and elaborate prognosis. Specific chromosome translocations have been identified for hematologic malignancy. The breakpoints of several of these translocations have been cloned. Several loci of oncogene have been identified and sequenced.  Molecular genetic analysis will replace cytogenetic analysis and shift the requirement for studying metaphase cells. Therefore, chromosome analysis in genetic disease and cancer should be attained with advanced molecular techniques, such as Fluorescence In Situ Hybridization (FISH) and microarray CGH analysis.  Cytogenetic analysis is still useful and applicable in genetic disease diagnosis, sexual assignment, and hematologic malignancy in the laboratory with minimal equipments. Molecular analysis as a part of health care services in Indonesia has been limited in research centers in university setting; therefore, a comprehensive diagnosis with genetic analysis has often been improbable.
Sikap Orang Tua Terhadap Penerimaan Konseling Genetika Pada Down Syndrome Niken Safitri Dyan K; Costrie G. W; Sultana MH Faradz
Jurnal Keperawatan Anak Vol 2, No 1 (2014): Jurnal Keperawatan Anak
Publisher : Jurnal Keperawatan Anak

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (309.773 KB)

Abstract

Background: Genetics counseling can improve individual knowledge and decrease the level of anxiety. More information about genetic diseases received by individu will make them more comfortable because of the certainty. However, the low of public awareness and understanding of issues concerning the genetic disease resulted in the unrecognized the existence of genetic counseling. Research on how attitudes towards genetic counseling in families with Down syndrome child are felt necessary. This study aims to determine parents’ attitudes towards receiving genetic counseling of Down syndrome. Methods: A quantitative approach used questionnaire was applied cross-sectionally to parents of child with Down syndrome in one special school Semarang. Sample was determined by purposive sampling. Univariate and bivariate analysis were performed to analyze data. Results: A total of 51 respondents participated in this study. The results showed that the majority of respondents (84.3%) supported a genetic counseling session on Down syndrome. Most of the respondents (98.0%) had a positive attitude toward a child with Down syndrome. Based on the bivariate analysis, there was no significant difference (p-value = 0.416) between father and mother attitudes toward receiving genetic counseling of Down syndrome. Conclusion: Most of the respondents were interested in genetic counseling session although they did not know about it previously.
Dilemma of presymptomatic testing in children with history of late onset neurodegenerative spinocerebellar ataxia in Indonesia Nydia Rena Benita Sihombing; Tri Indah Winarni; Maria Belladonna; Annastasia Ediati; Sultana MH Faradz
Journal of Biomedicine and Translational Research Vol 8, No 1 (2022): April 2022
Publisher : Faculty of Medicine, Universitas Diponegoro

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14710/jbtr.v1i1.13032

Abstract

Background: Spinocerebellar ataxia (SCA) is a late onset neurodegenerative disorder in which coordination and balance are affected. Although many international guidelines have been established regarding presymptomatic testing, it is still a grey area in Indonesia. We report two large families with advanced stages of SCA who underwent presymptomatic genetic testing in children along counseling process.Case presentation: Thorough examination was performed, including pedigree construction, physical and neurological examination, gene mutation analyses for patients, and presymptomatic testing for family members, including children. SCA3/MJD1 gene mutation analysis was done in both cases, and a full penetrance CAG repeat expansion was found in both affected patients. Two different outcomes were observed in the offspring, who were both children. The risk and consequences of positive results had been explained in a counseling session to family members, who decided to keep the information until the child would have reached legally adult age.Conclusions: In developing countries such as Indonesia, problems arose due to ethical issues, knowledge of genetic diseases, and inaccessible molecular diagnostics. Culture, religion and tribe diversities may create additional challenges. These cases emphasize the need for careful consideration of presymptomatic testing in children, especially in complicated situations where psychological and ethical issues should be addressed.