14q12q13.3 Deletion Diagnosed Using Chromosomal Microarray Analysis in an Infant Showing Seizures, Hypoplasia of the Corpus Callosum, and Developmental Delay

14q12q13.3 Deletion is a rare microdeletion syndrome associated with neurodevelopmental delay, failure to thrive, seizures, and abnormal brain development. Symptoms vary depending on the sites of gene deletion, and establishing the diagnosis is often difficult, as the condition cannot be detected with routine chromosome analysis. In this report, we present a patient with intrauterine growth retardation, microcephaly, muscle weakness, seizures, and hypoplasia of the corpus callosum who underwent diagnostic tests, including karyotyping in the neonatal period without leading to a specific diagnosis. The patient was confirmed with a serious developmental disorder, and a chromosomal microarray analysis was performed at 8 months of age, revealing a 14q12q13.3 deletion. In this case, the condition was diagnosed in early infancy, in contrast to previously reported cases, and the patient had diverse and severe symptoms. Establishing the diagnosis of 14q12q13.3 deletion syndrome allows better management of patient care and genetic counseling for the parents.

14q12q13.3 Deletion Diagnosed Using Chromosomal Microarray Analysis in an Infant Showing Seizures, Hypoplasia of the Corpus Callosum, and Developmental Delay

14q12q13.3 Deletion is a rare microdeletion syndrome associated with neurodevelopmental delay, failure to thrive, seizures, and abnormal brain development. Symptoms vary depending on the sites of gene deletion, and establishing the diagnosis is often difficult, as the condition cannot be detected with routine chromosome analysis. In this report, we present a patient with intrauterine growth retardation, microcephaly, muscle weakness, seizures, and hypoplasia of the corpus callosum who underwent diagnostic tests, including karyotyping in the neonatal period without leading to a specific diagnosis. The patient was confirmed with a serious developmental disorder, and a chromosomal microarray analysis was performed at 8 months of age, revealing a 14q12q13.3 deletion. In this case, the condition was diagnosed in early infancy, in contrast to previously reported cases, and the patient had diverse and severe symptoms. Establishing the diagnosis of 14q12q13.3 deletion syndrome allows better management of patient care and genetic counseling for the parents.

Phenotypic Analysis of Korean Patients with Abnormal Chromosomal Microarray in Patients with Unexplained Developmental Delay/Intellectual Disability

PURPOSE: The present study aimed to investigate chromosomal microarray (CMA) and clinical data in patients with unexplained developmental delay/intellectual disability (DD/ID) accompanying dysmorphism, congenital anomalies, or epilepsy. We also aimed to evaluate phenotypic clues in patients with pathogenic copy number variants (CNVs). MATERIALS AND METHODS: We collected clinical and CMA data from patients at Konyang University Hospital between September 2013 and October 2014. We included patients who had taken the CMA test to evaluate the etiology of unexplained DD/ID. RESULTS: All of the 50 patients identified had DD/ID. Thirty-nine patients had dysmorphism, 19 patients suffered from epilepsy, and 12 patients had congenital anomalies. Twenty-nine of the 50 patients (58%) showed abnormal results. Eighteen (36%) were considered to have pathogenic CNVs. Dysmorphism (p=0.028) was significantly higher in patients with pathogenic CNVs than in those with normal CMA. Two or more clinical features were presented by 61.9% (13/21) of the patients with normal CMA and by 83.3% (15/18) of the patients with pathogenic CMA. CONCLUSION: Dysmorphism can be a phenotypic clue to pathogenic CNVs. Furthermore, pathogenic CNV might be more frequently found if patients have two or more clinical features in addition to DD/ID.

Identifying the KAT6B Mutation via Diagnostic Exome Sequencing to Diagnose Say-Barber-Biesecker-Young-Simpson Syndrome in Three Generations of a Family

Diagnostic exome sequencing (DES) is a powerful tool to analyze the pathogenic variants leading to development delay (DD) and intellectual disability (ID). Recently, heterozygous de novo mutation of the histone acetyltransferase encoding gene KAT6B has been recognized as causing a syndrome with congenital anomalies and intellectual disability, namely Say-Barber-Biesecker-Young-Simpson (SBBYS) syndrome. Here we report a case of SBBYS syndrome in a third generation Korean family affected with a missense mutation in KAT6B, c.2292C>T p.(His767Tyr) identified by DES. This is the first confirmed familial inherited mutation of the KAT6B reported worldwide. Our case emphasizes again the importance of basic physical examination and taking a family history. Furthermore, advances in genetic diagnostic tools are becoming key to identifying the etiology of DD and ID. This allows a physiatrist to predict the disease's clinical evolution with relative certainty, and offer an appropriate rehabilitation plan for patients.

Ocular Abnormality of Korean Patients with Molecular Genetically Confirmed Gaucher Disease

PURPOSE: To investigate the ophthalmologic manifestations of Korean patients with Gaucher disease. METHODS: Clinical records of 5 patients who were referred to the pediatric ophthalmology clinic of Seoul National University Bundang Hospital after diagnosis of Gaucher disease at the genetics clinic of Ajou University Hospital between 2007 and 2008 were retrospectively reviewed. RESULTS: Five patients with type 3 Gaucher disease had hepatosplenomegaly and oculomotor apraxia, and 4 patients had growth and developmental delay. The most commonly detected genetic mutation was L444P. In addition, P201H, F2131, R257Q, and D315E+Rec 1b were identified. Five patients had oculomotor apraxia and limitation of abduction, and 4 patients had esotropia. One of the 4 patients who showed combined limitation of abduction, oculomotor apraxia, and esotropia, yet did not have growth and developmental delay. CONCLUSIONS: Most of the patients who were referred for ocular motor abnormalities with Gaucher disease showed a limitation of abduction, oculomotor apraxia, and esotropia. In patients with a limitation of abduction, oculomotor apraxia, and esotropia, Gaucher disease should be considered. Ophthalmologic examination is essential for subtyping and prognosing Gaucher disease.

Strabismus and Poor Stereoacuity Associated with Kabuki Syndrome

Kabuki syndrome is characterized by long palpebral fissures, large ears, a depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation. There have been few prior detailed descriptions of strabismus or stereopsis in these patients. We report a patient with Kabuki syndrome who showed small-angle strabismus and poor stereopsis. This case illustrates the need for patients with a diagnosis of Kabuki syndrome to have an ophthalmologic evaluation. Strabismus associated with Kabuki syndrome may have a small angle that can be easily overlooked.

Genetic Counseling in Korean Health Care System

Over the years Korean health care system has improved in delivery of quality care to the general population for many areas of the health problems. The system is now being recognized in the world as the most cost effective one. It is covered by the uniform national health insurance policy for which most people in Korea are mandatory policy holders. Genetic counseling service, however, which is well recognized as an integral part of clinical genetics service deals with diagnosis and management of genetic condition as well as genetic information presentation and family support, is yet to be delivered in comprehensive way for the patients and families in need. Two major obstacles in providing genetic counseling service in korean health care system are identified; One is the lack of recognition for the need for genetic counseling service as necessary service by the national health insurance. Genetic counseling consumes a significant time in delivery and the current very low-fee schedule for physician service makes it very difficult to provide meaningful service. Second is the critical shortage of qualified professionals in the field of medical genetics and genetic counseling who can provide the service of genetic counseling in clinical setting. However, recognition and understanding of the fact that the scope and role of genetic counseling is expanding in post genomic era of personalized medicine for delivery of quality health care, will lead to the efforts to overcome obstacles in providing genetic counseling service in korean health care system. Only concerted efforts from health care policy makers of government on clinical genetics service and genetic counseling for establishing adequate reimbursement coverage and professional communities for developing educational program and certification process for professional genetic counselors, are necessary for the delivery of much needed clinical genetic counseling service in Korea.

Hereditary Palmoplantar Keratoderma and Deafness Resulting from Genetic Mutation of Connexin 26

Gap junctions, which mediate rapid intercellular communication, consist of connexins, small transmembrane proteins that belong to a large family of proteins found throughout the species. Mutations in the GJB2 gene, encoding Connexin 26, can cause nonsyndromic autosomal recessive or dominant hearing loss with or without skin manifestations. A 3-yr-old Korean female and her mother presented to our clinic with diffuse hyperkeratosis of the palms and soles (May 3, 2007). Skin biopsies from the soles of both patients demonstrated histopathological evidence of palmoplantar keratoderma. The patient and a number of her maternal family members also had congenital hearing loss. The combination of congenital hearing loss and palmoplantar keratoderma, inherited as an autosomal dominant trait, led us to test for a mutation in the GJB2 gene in both patients. The results showed the R75W mutation of the GJB2 gene in both. In conclusion, the simultaneous occurrence of a GJB2 mutation in a mother and daughter suggests that R75W mutation cause autosomal dominant hearing loss presenting with palmoplantar keratoderma. To the best of our knowledge, this is the first report of a GJB2 mutation associated with syndromic autosomal dominant hearing loss and palmoplantar keratoderma in a Korean family.

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

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.

Loss of Y Chromosome in the Malignant Peripheral Nerve Sheet Tumor of a Patient with Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is one of the most commonly inherited autosomal dominant disorders. In order to determine whether genomic alterations and/or chromosomal aberrations involved in the malignant progression of NF1 were present in a Korean patient with NF1, molecular and cytogenetic analyses were performed on the pathologically normal, benign, and malignant tissues and primary cells cultured from those tissues of the patient. The comparative genomic hybridization (CGH) array revealed a Y chromosome loss in the malignant peripheral nerve sheet tumor (MPNST) tissue. G-banding analysis of 50 metaphase cells showed normal chromosomal patterns in the histopathologically normal and benign cultured cells, but a mosaic Y chromosome loss in the malignant cells. The final karyotype for the malignant cells from MPNST tissue was 45,X,-Y[28]/46,XY[22]. The data suggest that the somatic Y chromosome loss may be involved in the transformation of benign tumors to MPNSTs.

A Study of Guidelines for Genetic Counseling in Preimplantation Genetic Diagnosis (PGD)

PURPOSE: Preimplantation genetic diagnosis (PGD), also known as embryo screening, is a pre-pregnancy technique used to identify genetic defects in embryos created through in vitro fertilization. PGD is considered a means of prenatal diagnosis of genetic abnormalities. PGD is used when one or both genetic parents has a known genetic abnormality; testing is performed on an embryo to determine if it also carries the genetic abnormality. The main advantage of PGD is the avoidance of selective pregnancy termination as it imparts a high likelihood that the baby will be free of the disease under consideration. The application of PGD to genetic practices, reproductive medicine, and genetic counseling is becoming the key component of fertility practice because of the need to develop a custom PGD design for each couple. MATERIALS AND METHODS: In this study, a survey on the contents of genetic counseling in PGD was carried out via direct contact or e-mail with the patients and specialists who had experienced PGD during the three months from February to April 2010. RESULTS: A total of 91 persons including 60 patients, 49 of whom had a chromosomal disorder and 11 of whom had a single gene disorder, and 31 PGD specialists responded to the survey. Analysis of the survey results revealed that all respondents were well aware of the importance of genetic counseling in all steps of PGD including planning, operation, and follow-up. The patient group responded that the possibility of unexpected results (51.7%), genetic risk assessment and recurrence risk (46.7%), the reproduction options (46.7%), the procedure and limitation of PGD (43.3%) and the information of PGD technology (35.0%) should be included as a genetic counseling information. In detail, 51.7% of patients wanted to be counseled for the possibility of unexpected results and the recurrence risk, while 46.7% wanted to know their reproduction options (46.7%). Approximately 96.7% of specialists replied that a non-M.D. genetic counselor is necessary for effective and systematic genetic counseling in PGD because it is difficult for physicians to offer satisfying information to patients due to lack of counseling time and specific knowledge of the disorders. CONCLUSIONS: The information from the survey provides important insight into the overall present situation of genetic counseling for PGD in Korea. The survey results demonstrated that there is a general awareness that genetic counseling is essential for PGD, suggesting that appropriate genetic counseling may play a important role in the success of PGD. The establishment of genetic counseling guidelines for PGD may contribute to better planning and management strategies for PGD.

A Study on Genetic Counseling Curriculum, Accreditation of the Training Program, and the Certification Process of Genetic Counselors in Korea

PURPOSE: This study was undertaken to provide the framework for development of a genetic counseling training program, and an accreditation and certification process suitable for non-M.D. genetic counselors in Korea. MATERIALS AND METHODS: Global standards of genetic counseling curriculums, training program accreditation (TPA), and the certification process for genetic counselors (CPGC) in the U.S.A and Japan were reviewed, and a questionnaire survey was performed to elicit opinions among health-care providers including physicians, nurses, technicians, researchers, and educators. In addition, input from professional communities, including the Korean Society of Medical Genetics (KSMG) and Institute for Genetic Testing Evaluation, was sought in formulating the framework of this study. RESULTS: Comparison of U.S.A. and Japan educational systems showed similarities in curriculum, accreditation, and certification programs. Analysis of 117 respondents opinions showed a high level of agreement in the area of global standards; 88% indicated that KSMG should be in charge of TPA and CPGC, while 77% favored a certification exam composed of both written exam and interview components. CONCLUSION: Based upon this study we propose that the KSMG should be in charge of providing the TPA and CPGC for non-MD genetic counselors. Requirements for the entrance to a Master's degree genetic counseling program should be open to successful four year undergraduate students in all areas, provided the candidates demonstrate the abilities to master the graduate level of study in human genetics, clinical genetics, statistics, psychology, and other required subjects. Eligibility for certification should include qualified candidates of genetic counseling with no formally approved education, but a sufficient amount of clinical experience, in addition to accredited program graduates. Certification examinations should be carried out every two years and the certification should be good for five years, as is the case in Japan.

Fragile X Syndrome in Korea: A Case Series and a Review of the Literature

The purposes of this study were to present DNA analysis findings of our case series of fragile X syndrome (FXS) based on methylation-specific polymerase chain reaction (MS-PCR), PCR, and Southern blotting alongside developmental characteristics including psychological profiles and to review the literature on FXS in Korea. The reports of 65 children (male:female, 52:13; age, 6.12+/-4.00 yrs) referred for the diagnosis of FXS over a 26-months period were retrospectively reviewed for the identification of full mutation or premutation of fragile X mental retardation 1 (FMR1). Among the 65 children, there were 4 boys with full mutation, and one boy showed premutation of FMR1, yielding a 6.15% positive rate of FXS. All 4 children with full mutation showed significant developmental delay, cognitive dysfunction, and varying degrees of autistic behaviors. The boys with premutation showed also moderate mental retardation, severe drooling, and behavioral problems as severe as the boys with full mutation. Thirteen articles on FXS in Korea have been published since 1993, and they were reviewed. The positive rate of FXS was in the range of 0.77-8.51%, depending on the study groups and the method of diagnosis. Finally, the population-based prevalence study on FXS in Korea is required in the near future.

Molecular diagnosis of fragile X syndrome in a female child

PURPOSE: Fragile X syndrome (FXS) is the most common heritable cause of cognitive impairment. FXS is caused by hyperexpansion and hypermethylation of a polymorphic CGG trinucleotide repeat in the 5' untranslated region of the fragile X mental retadation-1(FMR1) gene. Combination of Southern blotting and simple polymerase chain reaction(PCR) amplification of the FMR1 repeat region is commonly used for diagnosis in females. To give a definite diagnosis in a female child suspected of having FXS, we carried out the molecular diagnostic test for FXS using the recently developed Abbott Molecular Fragile X PCR Kit. METHODS: The PCR amplification of the FMR1 repeat region was performed using the Abbott Mdecular Fragile X PCR Kit. The amplified products were analyzed by size-separate analysis on 1.5% agarose gels and by DNA fragment analysis using Gene scan. RESULTS: Agarose gel and Gene scan analyses of PCR products of the FMR1 repeat region showed that the patient had two heterozygous alleles with a normal 30 repeats and full mutation of >200 repeats whereas her mother had two heterozygous alleles with the normal 30 repeats and premutation of 108 repeats, suggesting that the premutation of 108 repeats in her mother may have led to the full mutation of >200 repeats in the patient. CONCLUSION: We diagnosed FXS in a female patient using a simplified molecular diagnostic test. This commercially available diagnostic test for FXS, based on PCR, may be a suitable alternative or complement method to Southern blot analysis and PCR analysis and/or methylation specific(MS)-PCR analysis for the molecular diagnosis of FXS in both males and females.

A Case of Birt-Hogg-Dube Syndrome

Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominant genodermatosis characterized by cutaneous hair follicle tumors (fibrofolliculoma or trichodiscoma), pulmonary cysts, and increased risk of renal neoplasia. The genetic alteration for BHDS has been mapped to chromosome 17p12q11, and the gene in this region has been cloned and believed to be responsible for the BHDS. Mutations in the BHD gene (also known as FLCN) have been described in the patients with BHDS. We present a case of a 30-yr-old Korean woman with multiple mildly pruritic papules on her face and neck area. The patient had several firm, flesh-colored, dome-shaped, papular lesions measuring between 2 to 5 mm. Except for a history of pneumothorax her medical records were not remarkable. Mutation analysis of the BHD gene was performed, and a novel deletion mutation (p.F519LfsX17 [c.1557delT]) causing truncation of the gene product, folliculin, was found in the exon 14. The actual incidence of BHDS is unknown, but it is most likely underdiagnosed. So it is imperative that doctors recognize the skin lesions of BHDS and institute proper screening to detect other manifestations of the disease. Here, we report a case of BHDS with a novel mutation, which is the first report in Korea.

Challenge of Personalized Medicine in the Genomic Era

"Personalized medicine," the goal of which is to provide better clinical care by applying patient's own genomic information to their health care is a global challenge for the 21st century "genomic era." This is especially true in Korea, where provisions for clinical genetic services are inadequate for the existing demand, let alone future demands. Genomics-based knowledge and tools make it possible to approach each patient as a unique biological individual, which has led to a paradigm-shift in medical practice, giving it more of a predictive focus as compared with current treatment oriented approach. With recent advancements in genomics, many genetic tests, such as susceptibility genetic tests, have been developed for both rare single gene diseases and more common multifactorial diseases. Indeed, genetic tests for presymtomatic individuals and genetic tests for drug response have become widely available, and personalized medicine will face the challenge of assisting patients who use such tests to make appropriate and wise use of genetic risk assessment. A major challenge of genomic medicine lies in understanding and communicating disease risk in order to facilitate and support patients and their families in making informed decisions. Establishment of a health care system with provisions for genetic counseling as an integral part of health care service, in addition to genomic literacy of health care providers, is vital to meet this growing challenge. Realization of the promise of personalized medicine in the era of genomics for improvement of health care is dependent on further development of next generation sequencing technology and affordable sequencing test costs. Also necessary will be policy development concerning the ethical, legal and social issues of genomic medicine and an educated and ready medical community with clinical practice guidelines for genetic counseling and genetic testing.

Retraction

No abstract available.

Genetic counseling in Korean health care system

Unprecedented amount of genetic information being generated from the result of Human Genome Project (HGP) and advances in genetic research is already forcing changes in the paradigm of health and disease. The ultimate goal of genetic medicine is to use genetic information and technology to develop new ways of treatment or even prevention of the disease on an individual level for 'personalized medicine'. Genetics is playing an increasingly important role in the diagnosis, monitoring and management of common multifactorial diseases in addition to rare single-gene disorders. While wide range of genetic testing have provided benefits to patients and family, uncertainties surrounding test interpretation, the current lack of available medical options for the diseases, and risks for discrimination and social stigmatization may remain to be resolved. However an increasing number of genetic tests are becoming commercially available, including direct to consumer genetic testing, yet public is often unaware of their clinical and social implications. The personal nature of information generated by a genetic test, its power to affect major life decisions and family members, and its potential misuse raise important ethical considerations. Therefore appropriate genetic counseling is needed for patient to be informed with the benefits, limitations and risks of genetic tests, prior to informed consent for the tests. Physician also should be familiar with the legal and ethical issues involved in genetic testing to tell patients how well a particular genetic risk factor relates with likelihood of disease, and be able to provide appropriate genetic counseling. Genetic counseling become a mandatory requirement as global standard for many genetic testing such as prenatal diagnosis, presymtomatic DNA diagnostic tests and cancer susceptibility gene test for familial cancer syndrome. In oder to meet the challenge of genetic medicine of 21 century in korean health care system, professional education program and certification board for medical genetics specialist including non-MD genetic counselors should be addressed by medical society and regulatory policy of national health insurance reimbursement for genetic counseling to be in place to promote the implementation of clinical genetic service including genetic counseling for proper genetic testing.

Spinocerebellar ataxia 7 (SCA7)

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases, clinically and genetically heterogeneous, characterized by degeneration of spinocerebellar pathways with variable involvement of other neural systems. At present, 27 distinct genetic forms of SCAs are known: SCA1-8, SCA10-21, SCA23, SCA25-28, DRPLA (dentatorubral-pallidoluysian atrophy), and 16q-liked ADCA (autosomal dominant cerebellar ataxia). Epidemiological data about the prevalence of SCAs are restricted to a few studies of isolated geographical regions, and most do not reflect the real occurrence of the disease. In general a prevalence of about 0.3-2 cases per 100,000 people is assumed. As SCA are highly heterogeneous, the prevalence of specific subtypes varies between different ethnic and continental populations. Most recent data suggest that SCA3 is the commonest subtype worldwide; SCA1, SCA2, SCA6, SCA7, and SCA8 have a prevalence of over 2%, and the remaining SCAs are thought to be rare (prevalence 450 CAG repeats. Immunoblott analysis demonstrated that ataxin-7 is widely expressed but that expression levels vary among tissues. Instability of expanded repeats is more pronounced in SCA7 than in other SCA subtypes and can cause substantial lowering of age at onset in successive generations termed 'anticipation' so that children may become diseased even before their parents develop symptoms. The strong anticipation in SCA7 and the rarity of contractions should have led to its extinction within a few generations. There is no specific drug therapy for this neurodegenerative disorder. Currently, therapy remains purely symptomatic. Cellular models and SCA7 transgenic mice have been generated which constitute valuable resources for studying the disease mechanism. Understanding the pathogenetic mechanisms of neurodegeneration in SCAs should lead to the identification of potential therapeutic targets and ultimately facilitate drug discovery. Here we summarize the clinical, pathological, and genetic aspects of SCA7, and review the current understanding of the pathogenesis of this disorder. Further, we also review the potential therapeutic strategies that are currently being explored in polyglutamine diseases.

The spectrum of 5p deletion in Korean 20 patients with Cri du chat syndrome

PURPOSE: Cri-du-Chat syndrome (CdCs) is a rare but clinically recongnizable condition with an estimated incidence of 1:50,000 live births. The clinical characteristics of the syndrome include severe psychomotor and mental retardation, microcephaly, hypertelorism, hypotonia, and slow growth. Also the size of the chromosome 5p deletion ranges were known from the region 5p13 to the terminal region. In this study, we report the spectrum of 5p deletion in Korean 20 pts. with CdCs and genotype-phenotype associations in CdCs. METHODS: In order to delineate genotype-phenotype correlation, molecular cytogenetic studies including GTG banding and clinical characterization were performed on Korean 20 pts with CdCs including parents. CGH array and Fluorescence in situ hybridization (FISH) analysis were used to confirm a terminal deletion karyotype and map more precisely the location of the deletion breakpoint. RESULTS: Molecular analysis of the spectrum of 5p deletion revealed 9 pts (45%) with a del (5)(p14), 7 pts. (35%) a del (5)(p13), 3 pts. (15%) a del (5)(p15.1) and 1 pt. (5%) a del (5)(p15.2) in 20 pts with CdCs. 4(20%)pts were identified to have additional chromosome abnormalites of deficiency and duplication involving chromosomes of 6, 8, 18, & 22. Parental study identified 3 familial case (2 paternal and 1 maternal origin) showing parents being a balanced translocation carrier. And the comparison study of the deletion break points among these 20 pts. with their phenotype has showed the varying clinical pheno-types in the CdCs critical region. CONCLUSION: The characterization of 5p deletion including parental study may help to delineate the genotypephenotype correlation in CdCs. Also these molecular cytogenetic analyses will be able to offer better information for accurate genetic diagnosis in CdCs and further make possible useful genetic counseling in pts. and family.