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Repetitive Pregnancy Loss in inv(22)(p13q12) Carrier.

Do Hoon KIM ; Jung Sook HA ; Jeong Ho RHEE

Journal of Genetic Medicine.2010;7(1):78-81.

Pericentric inversion is not rare in humans and is usually benign. However, pericentric inversion can lead to production of an unbalanced recombinant and might be a cause of repetitive pregnancy loss. Pericentric inversion of chromosome 22 is rare and only a few cases have been reported. We report a case of inv(22)(p13q12) carrier who had history of repetitive pregnancy loss including three spontaneous abortions and one fetal hydrops in which the chromosomal complement was rec(22)dup(22q) inv(22)(p13q12)mat. The maternal inv(22) and fetal rec(22) were confirmed by fluorescence in situ hybridization using region-specific probes (TUPLE1 on 22q11.2 and ARSA on 22q13). Because the identification of inv(22) or rec(22) in conventional karyotyping might be easily overlooked, great attention and additional molecular tests are required for accurate diagnosis of inv(22) and rec(22).
Abortion, Spontaneous ; Chromosomes, Human, Pair 22 ; Complement System Proteins ; Female ; Fluorescence ; Humans ; Hydrops Fetalis ; In Situ Hybridization ; Karyotyping ; Pregnancy

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Evaluation of Psychosocial Impact and Quality of Life in BRCA Mutation Family.

Sang Ah HAN ; Sairhee KIM ; Eunyoung KANG ; Tae Hyeon HA ; Jeong Hyun KIM ; Eun Joo YANG ; Jae Young LIM ; Wonshik HAN ; Dong Young NOH ; Sung Won KIM

Journal of Genetic Medicine.2010;7(1):67-77.

PURPOSE: The aims of this study are to evaluate psychological impact and quality of life according to the cancer diagnosis and mutation status in Korean families with BRCA mutations. MATERIALS AND METHODS: Seventeen affected carriers (AC), 16 unaffected carriers (UC) and 13 healthy non carriers (NC) from 13 BRCA mutation families were included in the study. Outcomes were compared with regard to depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory, STAI), optimism (Reevaluation of the Life Orientation test, LOT-R), knowledge of hereditary ovarian cancer, and quality of life (QoL) (SF-36v2 Health Survey, physical component score [PCS], mental component score [MCS]) among three groups. RESULT: Level of depression, optimism, and PCS were similar in AC, UC, and NC. Anxiety score was elevated in all three groups. MCS was significantly low in AC than in UC and NC (P =0.009, P =0.017). Knowledge of hereditary breast and ovarian cancer was high in AC than NC (P =0.001). MCS was significantly related to whether patient was affected by cancer (P =0.043) and has occupation (P = 0.008) or not in multivariable analysis. CONCLUSION: From this cross sectional study, psychological adverse effect was not related to the carrier status of BRCA mutation. Elevated anxiety in BRCA family members was observed but, independent to affection and the type of genetic mutation. AC showed low mental QoL. Further effort to understand psychological impact and QoL of genetic testing in BRCA family members is required for follow-up in clinical aspects.
Anxiety ; Breast ; Depression ; Genetic Counseling ; Genetic Testing ; Health Surveys ; Humans ; Occupations ; Orientation ; Ovarian Neoplasms ; Quality of Life

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Validation of QF-PCR for Rapid Prenatal Diagnosis of Common Chromosomal Aneuploidies in Korea.

Sung Hee HAN ; Jae Song RYU ; Jeong Wook AN ; Ok Kyoung PARK ; Hye Ryoung YOON ; Young Ho YANG ; Kyoung Ryul LEE

Journal of Genetic Medicine.2010;7(1):59-66.

PURPOSE: Quantitative fluorescent polymerase chain reaction (QF-PCR) allows for the rapid prenatal diagnosis of common aneuploidies. The main advantages of this assay are its low cost, speed, and automation, allowing for large-scale application. However, despite these advantages, it is not a routine method for prenatal aneuploidy screening in Korea. Our objective in the present study was to validate the performance of QF-PCR using short tandem repeat (STR) markers in a Korean population as a means for rapid prenatal diagnosis. MATERIALS AND METHODS: A QF-PCR assay using an Elucigene kit (Gen-Probe, Abingdon, UK), containing 20 STR markers located on chromosomes 13, 18, 21, X and Y, was performed on 847 amniotic fluid (AF) samples for prenatal aneuploidy screening referred for prenatal aneuploidy screening from 2007 to 2009. The results were then compared to those obtained using conventional cytogenetic analysis. To evaluate the informativity of STR markers, the heterozygosity index of each marker was determined in all the samples. RESULTS: Three autosomes (13, 18, and 21) and X and Y chromosome aneuploidies were detected in 19 cases (2.2%, 19/847) after QF-PCR analysis of the 847 AF samples. Their results are identical to those of conventional cytogenetic analysis, with 100% positive predictive value. However, after cytogenetic analysis, 7 cases (0.8%, 7/847) were found to have 5 balanced and 2 unbalanced chromosomal abnormalities that were not detected by QF-PCR. The STR markers had a slightly low heterozygosity index (average: 0.76) compared to those reported in Caucasians (average: 0.80). Submicroscopic duplication of D13S634 marker, which might be a unique finding in Koreans, was detected in 1.4% (12/847) of the samples in the present study. CONCLUSION: A QF-PCR assay for prenatal aneuploidy screening was validated in our institution and proved to be efficient and reliable. However, we suggest that each laboratory must perform an independent validation test for each STR marker in order to develop interpretation guidelines of the results and must integrate QF-PCR into the routine cytogenetic laboratory workflow.
Amniotic Fluid ; Aneuploidy ; Automation ; Chromosome Aberrations ; Cytogenetic Analysis ; Cytogenetics ; Female ; Korea ; Mass Screening ; Microsatellite Repeats ; Polymerase Chain Reaction ; Prenatal Diagnosis ; Y Chromosome

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Effective Method for Extraction of Cell-Free DNA from Maternal Plasma for Non-Invasive First-Trimester Fetal Gender Determination: A Preliminary Study.

Ji Hyae LIM ; So Yeon PARK ; Shin Young KIM ; Do JinDo KIM ; Mee Jin KIM ; Jae Hyug YANG ; Moon Young KIM ; Min Hyoung KIM ; Ho Won HAN ; Kyu Hong CHOI ; Hyun Mee RYU

Journal of Genetic Medicine.2010;7(1):53-58.

PURPOSE: To find the most effective method for extraction of cell-free DNA (cf-DNA) from maternal plasma, we compared a blood DNA extraction system (blood kit) and a viral DNA extraction system (viral kit) for non-invasive first-trimester fetal gender determination. MATERIALS AND METHODS: A prospective cohort study was conducted with maternal plasma collected from 44 women in the first-trimester of pregnancy. The cf-DNA was extracted from maternal plasma using a blood kit and a viral kit. Quantitative fluorescent-polymerase chain reaction (QF-PCR) was used to detect the SRY gene and AMEL gene. The diagnostic accuracy of the QF-PCR results was determined based on comparison with the final delivery records. RESULTS: A total of 44 women were tested, but the final delivery record was only obtained in 36 cases which included 16 male-bearing and 20 female-bearing pregnancies. For the blood kit and viral kit, the diagnostic accuracies for fetal gender determination were 63.9% (23/36) and 97.2% (35/36), respectively. CONCLUSION: In non-invasive first-trimester fetal gender determination by QF-PCR, using a viral kit for extraction of cf-DNA may result in a higher diagnostic accuracy.
Cohort Studies ; DNA ; DNA, Viral ; Female ; Genes, sry ; Humans ; Plasma ; Pregnancy ; Prospective Studies

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Cognitive Profile of Children with Williams Syndrome: Comparison with Children with Prader-Willi Syndrome and Down Syndrome.

Shin Young YIM ; Kye Hee CHO ; Hyon J KIM

Journal of Genetic Medicine.2010;7(1):45-52.

PURPOSE: The objectives were to examine following 2 questions related to cognitive profile for the children with Williams syndrome (WS); 1) Is there a significant advantage for verbal IQ over performance IQ in WS?; 2) Is there selective impairment in visuospatial ability in the children with WS? MATERIALS AND METHODS: Five children with WS with the age of 90.86+/-20.73 months were compared with 12 children with Prader-Willi syndrome (PWS) or Down syndrome (DS) with comparable age and IQ. RESULTS: All 5 children with WS showed intellectual disability whose mean scaled scores were 15.71+/-9.27 in verbal subtests and 14.29+/-7.50 in performance subtests, which did not show significant difference. There was no significant difference in the total sum of scaled scores of verbal subtests among WS, PWS and DS. There was no selective impairment in subtests which represented visuospatial tasks for the children with WS. However, the scaled score of object assembly was significantly lower in WS (2.29+/-0.95) compared to that of PWS (4.75+/-2.77; P<0.05). CONCLUSION: The general notion that the children with WS would be relatively strong in verbal function when compared with their overall cognitive function was not observed in this study. The verbal function of the children with WS was not better when compared to the children with DS or PWS. There was no selective impairment of visuospatial function in the children with WS at this age. However, the visuospatial function was significantly low in the children with WS only when compared to the children with PWS.
Child ; Down Syndrome ; Humans ; Imidazoles ; Intellectual Disability ; Nitro Compounds ; Prader-Willi Syndrome ; Williams Syndrome

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Phenotypic and Cytogenetic Delineation of Six Korean Children with Kabuki Syndrome.

Jung Min KO ; Jeong Min HWANG ; Hyon Ju KIM

Journal of Genetic Medicine.2010;7(1):37-44.

PURPOSE: Kabuki syndrome is a multiple congenital malformation syndrome with mental retardation. It was named after its characteristic appearance, a face resembling that of an actor in a Kabuki play. To date, six Korean cases of Kabuki syndrome have ever been reported. Here, we present the phenotypic and genetic characteristics of six patients with Kabuki syndrome. MATERIALS AND METHODS: Between 2003 and 2009, six Korean girls have been diagnosed and followed up as Kabuki syndrome at Center for Genetic Diseases of Ajou University Hospital. Their clinical and laboratory data were collected and analyzed by the retrospective review of medical records. RESULTS: All six patients showed the characteristic facial dysmorphism and developmental delay. Persistent fingertip pads were also found in all patients. Most patients showed postnatal growth retardation (83.3%) and hypotonia (83.3%). Opthalmologic problems were common, particularly for strabismus (83.3%). Congenital heart defects were present in three patients (50%). Skeletal abnormalities including 5th finger shortening (83.3%), clinodactyly (50%), joint hypermobility (50%) and hip dislocation (16.7%) were also observed. There was no patient who had positive family history for Kabuki syndrome. Cytogenetic and molecular cytogenetic analyses including karyotyping and array CGH could not reveal any underlying genetic cause of Kabuki syndrome. CONCLUSION: Korean patients with Kabuki syndrome showed a broad spectrum of clinical features affecting multiple organ systems. Although clinical manifestations of Kabuki syndrome have been well established, our results failed to detect recurrent chromosome aberrations which could cause Kabuki syndrome. Its natural history and genetic background remains to be further studied for providing appropriate management and genetic counseling.
Abnormalities, Multiple ; Child ; Chromosome Aberrations ; Cytogenetic Analysis ; Cytogenetics ; Face ; Fingers ; Genetic Counseling ; Heart Defects, Congenital ; Hematologic Diseases ; Hip Dislocation ; Humans ; Intellectual Disability ; Joint Instability ; Karyotyping ; Medical Records ; Muscle Hypotonia ; Natural History ; Retrospective Studies ; Strabismus ; Vestibular Diseases

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Hereditary Colorectal Cancer.

Duck Woo KIM

Journal of Genetic Medicine.2010;7(1):24-36.

Colorectal cancer is one of the most steeply increasing malignancies in Korea. Among 398,824 new patients recorded by the Korea Central Cancer Registry between 2003 and 2005, 47,915 cases involved colorectal cancers, accounting for 12.0% of all malignancies. In 2002, total number of colorectal cancer cases had accounted for 11.2% of all malignancies. Hereditary syndromes are the source of approximately 5% to 15% of overall colorectal cancer cases. Hereditary colorectal cancers are divided into two types: hereditary nonpolyposis colorectal cancer (HNPCC), and cancers associated with hereditary colorectal polyposis, including familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, juvenile polyposis, and the recently reported hMutYH (MYH)-associated polyposis (MAP). Hereditary colorectal cancers have unique clinical features distinct from sporadic cancer because these are due to germline mutations of the causative genes; (i) early age-of-onset of cancer, (ii) frequent association with synchronous or metachronous tumors, (iii) frequent association with extracolonic manifestations. The management strategy for patients with hereditary colorectal cancer is quite different from that for sporadic cancer. Furthermore, screening, genetic counseling, and surveillance for at-risk familial member are also important. A well-organized registry can plays a central role in the surveillance and management of families affected by hereditary colorectal cancers. Here, we discuss each type of hereditary colorectal cancer, focusing on the clinical and genetic characteristics, management, genetic screening, and surveillance.
Accounting ; Adenomatous Polyposis Coli ; Colorectal Neoplasms ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Counseling ; Genetic Testing ; Germ-Line Mutation ; Humans ; Korea ; Peutz-Jeghers Syndrome

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Molecular Genetic Diagnosis of Genetic Endocrine Diseases.

Jin Ho CHOI ; Gu Hwan KIM ; Han Wook YOO

Journal of Genetic Medicine.2010;7(1):16-23.

Many endocrine disorders have a genetic component. The genetic component is the major etiologic factor in monogenic disorders, while multiple genes in conjunction with environmental and lifestyle factors contribute to the pathogenesis in complex disorders. The development of the molecular basis of inherited endocrine diseases has undergone a dramatic evolution during the last two decades. The application of molecular technology allowed us to increase our understanding of endocrine diseases, and to impact on the practice of pediatric endocrinology related to diagnosis and genetic counseling. Identification of the mutation in the particular disease by genetic testing leads to precise diagnosis in the equivocal cases and prenatal diagnosis. However, clinicians should be cautious about determining therapeutic decisions solely on the basis of molecular studies, especially in the area of prenatal diagnosis and termination of pregnancy. This review describes an introduction to molecular basis of various inherited endocrine diseases and diagnosis by genetic testing.
Endocrine System Diseases ; Endocrinology ; Genetic Counseling ; Genetic Testing ; Life Style ; Molecular Biology ; Pregnancy ; Prenatal Diagnosis

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Genetic Variations of Congenital Hypothyroidism.

Yong Wha LEE ; Dong Hwan LEE

Journal of Genetic Medicine.2010;7(1):9-15.

Congenital hypothyroidism (CH) is detected at a rate of 1 in 3,000 to 4,000 live births, making it the most common congenital endocrine disorder worldwide. CH is most commonly caused by defects in thyroid development leading to thyroid dysgenesis or dyshormonogenesis. Congenital hypothyroidism is usually sporadic, but up to 2% of cases of thyroid dysgenesis are familial, and CH caused by organification defects is often inherited in a recessive manner. The candidate genes associated with this genetically heterogeneous disorder fall into two main groups: those causing thyroid gland dysgenesis and those causing dyshormonogenesis. Genes associated with thyroid gland dysgenesis include the TSHR gene in non-syndromic CH, and Gsa and the thyroid transcription factor (TTF-1, TTF-2, and Pax-8) genes, which are associated with different complex syndromes that include CH. Among genes associated with dyshormonogenesis, the TPO and TG genes were initially described, and more recently PDS, NIS, and THOX2 gene defects. There is some evidence for a third group of CH conditions associated with iodothyronine transporter defects that are, in turn, associated with severe neurological sequelae.
Congenital Hypothyroidism ; Genetic Variation ; Live Birth ; Thyroid Dysgenesis ; Thyroid Gland ; Transcription Factors

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Genetic Risk Factors of Hemophilia A.

Ye Jee SHIM ; Kun Soo LEE

Journal of Genetic Medicine.2010;7(1):1-8.

Hemophilia A is a sex-linked recessive coagulation disorder associated with diverse mutations of the factor VIII gene and a variety of phenotypes. The type of mutation involved dictates the activity of factor VIII, and in turn the severity of bleeding episodes and development of alloantibodies against factor VIII (inhibitors). Missense mutations are the most common genetic risk factors for hemophilia A, especially mild to moderate cases, but carry the lowest risk for inhibitor development. On the other hand, intron 22 inversion is the most common mutation associated with severe hemophilia A and is associated with high risk of inhibitor formation. Large deletions and nonsense mutations are also associated with high risk of inhibitor development. Additional mutations associated with hemophilia A include frameshift and splice site mutations. It is therefore valuable to assess the mutational backgrounds of hemophilia A patients in order to to interpret their symptoms and manage their health problems.
Codon, Nonsense ; Factor VIII ; Hand ; Hemophilia A ; Hemorrhage ; Humans ; Introns ; Isoantibodies ; Mutation, Missense ; Phenotype ; Risk Factors

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