Medical Genetics Consultation Research Articles

Bilateral pheochromocytoma in patients with von Hippel–Lindau syndrome: clinical and molecular genetic features

Bilateral adrenal pheochromocytoma (PCС) is extremely rare in children, with major predisposing factors being multiple endocrine neoplasia type 2 and von Hippel–Lindau syndrome. In case of bilateral PCC with underlying von Hippel–Lindau syndrome, organ-preserving surgery is preferred in view of the low malignant potential of such neoplasms. We aimed to study clinical and molecular genetic features of patients with bilateral adrenal PCCs treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian Federation. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian Federation. The study included 20 patients with paraganglioma (PGL)/PCC (PPGL) who had received treatment (n = 17) or outpatient care (n = 3) at the Center over the period from 2012 to 2023. Bilateral adrenal PCC was diagnosed in 4 (20%) patients. In all these cases, the diagnosis was confirmed by histology. Molecular genetic testing was carried out at the Laboratory of Molecular Biology at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian Federation in order to search for germline pathogenic variants in PCC/PGL susceptibility genes. The median age of the four patients with bilateral adrenal PCC was 9.5 years (range 4.5–14.6 years). All the patients were male. In one patient, synchronous bilateral PCC/PGL was observed. In 100% of the cases, arterial hypertension was diagnosed at the onset of the primary disease and was treated with alpha-blockers as part of preparation for surgery. According to the results of a 24-hour urine biochemistry test, all the patients had at least a 4-fold increase above the upper limit of normal for normetanephrine levels. Molecular genetic testing using the multiplex ligation-dependent probe amplification method revealed a pathogenic germline variant in exon 3 of the VHL gene in all the children (4/4). Hereditary PPGL was proven in 2/4 (50%) patients. In all the cases, R0/R1 resection was achieved. Organ-sparing surgery on one/two adrenal glands was performed in 3/4 cases. One out of four (25%) patients developed a local relapse 18.4 months after diagnosis. The overall survival rate in this group was 100%, with a median follow-up time of 8.1 months (range 0.8–50.2 months). Bilateral adrenal PCC is a very rare childhood tumor. A medical genetic consultation is necessary to identify tumor predisposition syndromes. A multidisciplinary team discussion of a surgical strategy is recommended, with organ-sparing surgery on one or two adrenal glands being the treatment of choice that should be carried out at centers specializing in pediatric surgical oncology. Here, we report a rare clinical case of bilateral retroperitoneal PCC/PGL in a patient with von Hippel-Lindau syndrome. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

Pre-implantation Genetic Testing in Inherited Metabolic Diseases? Stateof- the-art and current challenges.

Inborn errors of metabolism (IEM) are genetic diseases involving congenital disorders of enzyme activities. Most follow Mendelian autosomal recessive inheritance and few follow mitochondrial inheritance. In many cases, after the birth of an affected child parents discover that have been the carriers for the condition and worry about the risk of recurrence in future offspring. Preimplantation genetic testing (PGT) can analyze embryos before their transfer to the uterus and prevent the transmission of hereditary conditions to descendants, however this procedure is of limited value in mtDNA conditions. The list of diseases currently approved for PGT were reviewed. The process for eligibility, was as for the Comissão Nacional Procriação Medicamente Assistida (CNPMA), of Portugal (PT). Review of international practices for Assisted Reproductive Techniques (ART) in IEM was carried out. As of 07.2022, 23 IEM diseases associated with deleterious variants in nDNA were approved for PGT in PT. Couples at risk for conditions not included in the list can solicit an evaluation from an expert committee, after a medical genetics consultation. To qualify for approval, diseases must cause significant suffering and/or premature death. Due to a greater number of solicitations many more IEM conditions have been approved for PGT across the world. ART for mtDNA is not available in PT. International expert centers include PGT for specific well documented variants and mitochondrial donation. PGT is a reliable approach to reduce the risk of transmission of a genetic condition to the offspring. The list of IEM disorders currently accepted for this technique in Portugal are small, but it is expanding, as many more diseases fit the necessary criteria. While appealing in theory, low success rates coupled with limited availability can be discouraging for patients. Genetic counselling is of paramount importance after the diagnosis of IEM diseases. It is important for both clinicians and patients to be made aware of the available reproductive options and their limitations.

Double Isochromosome X, a Rare Cytogenetic Variant of Turner Syndrome: A Case Report and a Review of the Literature.

Turner Syndrome (TS) is a genetic disorder caused by total or partial loss of an X chromosome. The isochromosome X (i(X)) is a known variant of TS, however, double i(X) is a very rare variant, reported very few times in the literature. We report on a rare case of TS with double i(X). This is an 11-year-old female patient , addressed to the medical genetics consultation for short stature and facial features suggestive of TS. We performed a constitutional postnatal karyotype from a peripheral blood sample, with lymphocyte culture, and an R band analysis, performed on 70 metaphases. Metaphases analysis in our patient identified the presence of three cell populations: 45,X[22]/46,X,i(X)(q10)[30]/47,X,i(X)(q10),i(X)(q10) [18]. The first has total chromosome X monosomy, the second with a normal X chromosome and one isochromosome of the long arm of the other X chromosome and the third with a normal X chromosome and two isochromosomes of the long arm of the X chromosome. A control cell culture was performed from a second blood sample of the patient and confirmed the abnormality. This paper will discuss this case in comparison with other rare cases described, as well as the formation of the double isochromosome, based on the literature.

Оценка эффективности секвенирования нового поколения в клинической практике медико-генетической консультации в ХМАО-Югре

Актуальность. Полноэкзомное секвенирование на основе NGS, принятое с 2016 г. в качестве аутсорсинговой услуги, все чаще используется в рутинной клинической практике окружной медико-генетической консультации (МГК). Оценка диагностических возможностей полноэкзомного секвенирования необходима для обоснования проведения NGS непосредственно в региональных клинических условиях. Цель: оценить эффективность диагностики генетических заболеваний у детей в ХМАО-Югра методом полноэкзомного секвенирования. Методы. Полноэкзомное секвенирование методом NGS, валидация данных NGS и анализ сегрегации в семье методом секвенирования по Сэнгеру. Результаты. Молекулярные диагнозы были установлены у 27% (27/100) детей, что соответствует данным, опубликованным в других источниках. Наследственные заболевания чаще диагностировались у лиц с аномалиями нервной, костной и дыхательной систем. Были выявлены преимущественно аутосомно-доминантные заболевания, среди которых наиболее частыми были нейрофиброматоз, несовершенный остеогенез, ахондроплазия. Анализ семейной сегрегации патологических вариантов выявил 5 новых вариантов в генах TSC1, KAT6A, ANKRD26, ARID1B, RPGRIP1. Background. NGS-based exome sequencing, accepted as an outsourced service since 2016, is increasingly being used in the routine clinical practice of our medical genetic counseling centre. Evaluation of the diagnostic capabilities of exome sequencing is necessary to substantiate the effectiveness of NGS in situ in regional clinical settings. Aim: to evaluate the effectiveness of diagnosing genetic diseases in children in Khanty-Mansi region using exome sequencing. Methods. Exome sequencing by NGS, validation of NGS data by Sanger sequencing, family segregation analysis by Sanger sequencing. Results. Molecular diagnoses were reported in 27% (27/100) of children, in line with data published elsewhere. The diagnoses were more often diagnosed in persons with anomalies of the nervous, skeletal and respiratory systems. Predominantly autosomal dominant diseases were identified, among which the most common were neurofibromatosis, osteogenesis imperfecta, achondroplasia. Family segregation revealed 5 new variants in the TSC1, KAT6A, ANKRD26, ARID1B, RPGRIP1 genes.

Ethics of Uncertainty As an Extension of Virtue Epistemology

Uncertainty can’t be understood without taking into account both properties of the problem situation and agent’s knowledge about it. The correspondence of knowledge and situation of decision-making is crucial for understanding the onto-epistemological nature of uncertainty. At the same time, this correspondence is the key topic in virtue epistemology, especially in its ‘non-classical’, regulatory, branch, related to works of R. Roberts and W.J. Wood. In this article, genetic consultation is chosen as an example of such a problematic situation since a doctor and a patient explicitly deal with the uncertainty of genetic risks. The problems of communication and joint decision-making in the context of medical-genetic consultation are comprehensively described in bioethics. At the same time, its social dimension is limited to the direct interaction of two individual agents, that allows us to use it as a model for constructing the ethics of uncertainty. In this article, four forms of uncertainty are identified: descriptive, normative and radical uncertainties, and translation uncertainty. Referring to the approaches of virtue epistemology, the author brings each of these forms into conformity with the proposed regulatory principle. The regulations assume that generating or disseminating knowledge under conditions of uncertainty require taking into account the incompleteness of the presented model of reality in its four aspects. A modelled fragment of reality could change in a predictable (descriptive uncertainty) or unexpected (radical uncertainty) way. The goals and values of a model’s user can not be hierarchically ordered, and may also change in the future (normative uncertainty). User’s interpretations of the model may be diverse, and can never be strictly defined by the intentions of the model’s author (indeterminancy of translation, or uncertainty whether success of co-reference is achieved).

Audit of Gastrointestinal Manifestations in Patients with Loeys–Dietz Syndrome and Vascular Ehlers–Danlos Syndrome

Loeys-Dietz syndrome (LDS) and vascular Ehlers-Danlos Syndrome (vEDS) are genetically heterogeneous heritable disorders of connective tissue. Both are multi-system disorders with dominant vascular pathology and associated gastrointestinal manifestations. To summarize the abdominal manifestations found in these two disorders in a cohort of patients seen at Mayo Clinic during a period of 25years. Data were collected via the advanced cohort explorer (ACE) of Mayo Clinic records from 1994 to 2018 in patients with vEDS or LDS confirmed by genetic testing and/or medical genetics consultation. We extracted information concerning gastrointestinal symptoms, abdominal hernias, and vascular manifestations or complications. We identified and reviewed records of 68 vEDS and 13 LDS patients. Patients were similar in age at diagnosis and gender distribution. Gastrointestinal symptoms were frequently reported in both disorders and largely similar, although altered bowel function was more prevalent in LDS patients. Hernias were present in similar proportions of patients with vEDS and LDS; however, ventral hernias were more frequent and more likely to be postoperative in vEDS than LDS. LDS patients had more arterial aneurysms overall (76.9% LDS vs. 58% vEDS, p = 0.02) and a higher proportion required arterial repair (69.2% LDS vs. 32.7% vEDS S, p = 0.03). Co-morbidities of autonomic dysfunction, psychopathology (most commonly anxiety, depression, adjustment disorder), and allergy were more prevalent in LDS than vEDS. Patients with vEDS and LDS had a propensity for gastrointestinal symptoms, abdominal hernias, and aneurysm formation, but repair for arterial rupture was more prevalent in LDS than EDS.

Benchmarking outcomes in the Neonatal Intensive Care Unit: Cytogenetic and molecular diagnostic rates in a retrospective cohort.

Genetic disease and congenital anomalies continue to be a leading cause of neonate mortality and morbidity. A genetic diagnosis in the neonatal intensive care unit (NICU) can be a challenge given the associated genetic heterogeneity and early stage of a disease. We set out to evaluate the outcomes of Medical Genetics consultation in the NICU in terms of cytogenetic and molecular diagnostic rates and impact on management. We retrospectively reviewed 132 charts from patients admitted to the NICU who received a Medical Genetics diagnostic evaluation over a 2 year period. Of the 132 patients reviewed, 26% (34/132) received a cytogenetic or molecular diagnosis based on the Medical Genetics diagnostic evaluation; only 10% (13/132) received a diagnosis during their admission. The additional 16% (21 patients) received their diagnosis following NICU discharge, but based on a genetic test initiated during hospital-stay. Mean time from NICU admission to confirmed diagnosis was 24 days. For those who received a genetic diagnosis, the information was considered beneficial for clinical management in all, and a direct change to medical management occurred for 12% (4/32). For those non-diagnosed infants seen in out-patient follow-up clinic, diagnoses were made in 8% (3/37). The diagnoses made post-discharge from the NICU comprised a greater number of Mendelian disorders and represent an opportunity to improve genetic care. The adoption of diagnostic tools, such as exome sequencing, used in parallel with traditional approaches will improve rate of diagnoses and will have a significant impact, in particular when the differential diagnosis is broad.

Bilateral choanal atresia in an adult woman with pycnodysostosis

Pycnodysostosis (PYCD, OMIM: 265800) is an uncommon, autosomal recessive condition, first described by Maroteaux and Lamy in 1962 (Maroteaux and Lamy 1962). PYCD is also known as Toulouse-Lautrec disease, after the French artist Henri de Toulouse-Lautrec who may have had the disease (Hodder et al. 2015). Responsible gene for this phenotype (CTSK) codes the enzyme cathepsin K that is important for normal osteoclasts' function. The characteristic features of pycnodysostosis are short stature, bone fragility with osteosclerosis, acro-osteolysis of the distal phalanges, delayed suture closure, obtuse mandibular angle, prominent eyes and brachydactyly. Craniofacial abnormalities such as maxillofacial malformations, narrow palate and dental anomalies frequently accompany pycnodysostosis. Airway problems have also been described in pycnodysostosis patients (Testani et al. 2014). Congenital choanal atresia was first described by Roederer in 1755 (Hengerer and Strome 1982). Choanal atresia can occur alone or it can be a component of other syndromes such as CHARGE syndrome, and other craniosynostosis syndromes (Crouzon syndrome, Pfeiffer syndrome etc.). Here, we describe a pycnodysostosis case with bilateral choanal atresia in addition to other findings. A 23-year-old woman from a consanguineous Turkish family was referred to us because of her craniofacial dysmorphism, short stature, unilateral hearing loss and bilateral choanal atresia. Clinical examination showed frontal bossing, bilateral frontotemporal grooving, proptosis, prominent nose, retro-micrognathia, narrow palate, wrinkled skin, brachydactyly, broad thumbs, bilateral sandal gap deformity (Fig. 1a). Her height was 133 cm, (below 3rd percentile) and her mental status seemed normal. Pedigree analysis showed autosomal recessive pattern with two more similar patients in the family. Radiographic examinations showed metopic craniosynostosis, open wide cranial sutures, hypoplasia of terminal phalanges and acro-osteolysis, sclerosis of vertebral bodies and anterior scalloping (spool-shaped vertebrae), Madelung deformity of forearm, and Erlenmayer flaks deformity of long bones (Fig. 1b–e). Genomic DNA was isolated from peripheral blood samples of the patient using MagnaPure LC DNA Isolation Kit-Large Volume and MagnaPure LC instrument (Roche Applied Science, Mannheim, Germany). CTSK gene mutation analysis was performed by sequencing of the coding exons and the exon-intron boundaries of the genes. Sequencing was carried out with Miseq V2 chemistry on MiSeq instrument (Illumina California, USA). Analysis was performed with IGV software. c.934C > T (p.R312X) homozygote mutation was found in the 8th exon of the CTSK gene. She had complained of nasal congestion and was refered to the otorhinolaryngology department. During endoscopic examination, bilateral choanal atresia with unilateral pin point perforation were found (Fig. 1f). On computed tomography, soft tissue was detected in the posterior portion of the nasal cavity, which was obliterated to choana and also open cranial sutures were seen (Fig. 1b,d). Endoscopic transnasal repair of choanal atresia was performed. Cathepsin K is a cysteine protease that plays an important role in degradation of collagen type I and other bone proteins (Motyckova and Fisher 2002). Cathepsin K is a major lysosomal protease in bone resorption that is highly expressed in osteoclasts. Pycnodysostosis is caused by homozygous or compound heterozygous mutations in the CTSK gene. In pycnodysostosis osteoclast numbers and demineralizing function are normal; however, degradation of the organic matrix is insufficient (Gelb et al. 1996). Various mutations in the CTSK gene were identified in patients. In our case, nonsense c.934C > T (p.R312X) homozygote mutation was observed and this mutation was reported previously in Turkish patients (Arman et al. 2014). This mutation occurs by changing of the C residue of CGA encoding arginine to T resulted in TGA, stop codon on CTSK gene. Choanal atresia is a congenital abnormality and it can be unilateral or bilateral. The bilateral defect is more rare and generally present in a newborn as a medical emergency. Hence, bilateral choanal atresia is uncommon in adults and there are only a few cases reported in the literature. Respiratory involvement, such as obstructive sleep apnea syndrome, upper airway narrowing and respiratory distress, is frequent in patients with pycnodysostosis (Testani et al. 2014). However, pycnodysostosis with bilateral choanal atresia have not been reported earlier in the literature. Choanal atresia can be a component of a genetic syndrome. Medical genetics consultation should be requested when choanal atresia is not isolated. None.

Mais do que uma insuficiência de crescimento: relato de caso

Introduction: Failure to thrive is a common reason for referral of children for pediatric consultation. There are many causes and the correct diagnosis is essential for the treatment and prevention of secondary complications. Although genetic diseases as a cause of failure to thrive are rare, awareness of this possibility is necessary. Case report: A 2-year-old boy, with history of intrauterine growth retardation and feeding difficulties from the neonatal period, was seen in a general practice consultation due to failure to thrive and global psychomotor developmental delay. In addition to these medical problems, the child had craniofacial dysmorphism, a stellate iris pattern, a hoarse voice, lax joints, and an overfriendly and talkative personality. The diagnosis of Williams syndrome was proposed. The patient was referred to a medical genetics consultation and the diagnosis was confirmed by demonstrating a chromosomal microdeletion at 7q11.23. The child was referred for appropriate follow-up of the child and his young parents received genetic counselling. Comment: The presence of psychomotor developmental delay and multiple physical anomalies should raise the possibility of a genetic syndrome as a cause of failure to thrive. Family physicians should have basic knowledge of genetic disorders to allow the recognition of clinical signs suggestive of inborn genetic diseases in order to enable early diagnosis and referral of the patient and the family for medical genetic consultation.

DNA DIAGNOSTICS AND MUTATION SPECTRUM OF THE GENE FBN1 IN MARFAN’S SYNDROME

Aim. The development of an optimal protocol for diagnostic search for mutations with the use of the new generation sequencing technique (NGS) and evaluation of the mutation spectrum in Russian selection of the patients with Marfan syndrome. Material and methods. Totally 32 patients included with Marfan syndrome. For 24 the direct sequencing was done by Sanger, of 24-32 exons FBN1. For 10 persons the analysis performed of coding exons and close introns regiones of the gene FBN1 with the preparation of fragmented libraries and performing of NGS on the IonTorrent platform. For 12 persons the mutations search was done with the use of automatically developed panel of Ampliseq primers for multiplex amplification of coding regions of genes that are responsible for the connective tissue development. Results. In investigation of 24-32 exones of FBN1 we found 3 replacements (p.C921R, p.C950S and p.I1048T). In complete analysis of FBN1 gene by fragmentation check of replacements we found 4 premature stop-codons (p.Y181*, p.R516*, p.Q1811*, p.R2776*) and 3 missense variants (C739W, p.C1095S, p. C2468R). In addition, there was deletion with the shift of translation frame and occurence of stop-codon in the 9th exon (c.661delT). In one female patient there was replacement variant c.4942+4A>G, with non-defined clinical significance. With the complete analysis of FBN1 using Ampliseq there were 2 premature codons found (р. Q520*, p.K2838*) and 2 deletions with the translation frame shift (c.40_49del, c.6751del). In 6 from 12 there were missense replacements found (p.N2144S, p.A986T, p.C2390S, p.С2276W, p.C1777R and p.C2363G). Conclusion. In the case of absense of the “hot spot” exons, invention of NGS allows for optimization the search of mutations even in such long genes as the FBN1. Medical-genetic consultation and DNA-diagnostics are the integral methods for multidisciplinary care.

PROSPECTS OF DIAGNOSTICS OF AUTISM SPECTRUM DISORDERS IN CHILDREN

The relevance of a problem of autism spectrum disorder in children and the modern view on etiology and pathogenesis of these states are revealed in the article. Autism classification according to the International classification of diseases of the 10th revision adopted in Russia and important changes of a new classifier of the American psychiatric association concerning autism spectrum disorders are considered. The difficulties connected with diagnostics of autism spectrum disorders in children, autism comorbidity and some other psychiatric nosologies and the necessity of detailed differential diagnostics for a circle of these diseases are mentioned. Autism spectrum disorders are presented from the point of view of clinical genetics, the necessity of medical genetic consultation in diagnosing is proved. Definition of complex and essential autism is given. A number of widespread genetic syndromes with the description of clinical characteristics and molecular genetic mechanisms underlying the pathogenesis is allocated in the group of complex autism. Difficulties of molecular genetic confirmation of the diagnosis are revealed, the algorithm of search of mutations and the short description of methods of diagnostics are given. The efficiency of standard procedure of molecular genetic diagnostics at each stage, according to literary data, is shown in the group of children with essential autism. The opportunities and advantages of a method of the chromosomal micromatrix analysis as one of available modern methods of molecular genetic diagnostics in the group of children with autism spectrum disorders are highlighted on the example of extended microdeletion and microduplicational syndromes.

Presentation and Treatment of Subfertile Men with Balanced Translocations: The Cleveland Clinic Experience

Introduction: Balanced chromosomal translocations are a relatively common (2–7%) finding among infertile couples. We report clinical features of males with translocations at our institution. Materials and Methods: Data was collected on men presenting for infertility evaluation between July 2006 March 2010, including presentation, medical history, and infertility treatments. Criteria for genetic evaluation, consisting of karyotype and Y-linked microdeletion assay, included severe oligozoospermia or azoospermia (sperm concentration < 2.5×106/ml) or a history of recurrent miscarriages. Results: Of the 4,612 patients in our male infertility clinic 306 met criteria for genetic evaluation. Three patients had a balanced translocation, of which 2 had Robertsonian translocations, and 1 had a balanced translocation. One patient had normal bulk semen parameters, normal volume azoospermia, and oligoasthenoteratozoospermia. All patients were offered medical genetics consultation. Potential pregnancy outcomes were evaluated using a predictive software package. One patient had intratubular germ cell neoplasia and underwent orchiectomy; subsequent fertility evaluation has been deferred. The other 2 are considering in-vitro fertilization with pre-implantation genetic evaluation. Conclusions: Given the low incidence of balanced translocations detected in our population, better clinical indicators other than semen parameters or history of recurrent pregnancy loss are needed to determine screening for this finding.

Confirmation de la forte prévalence au Maroc de la mutation homozygote c.144delC du gène aurora kinase C (AURKC) dans les tératozoospermies avec spermatozoïdes macrocéphales

To confirm the recurrent character of the mutation c.144delC in the aurora kinase C (AURKC) gene in Morocco and determine the indication and the interest of the research of this anomaly. We looked for the mutation c.144delC in the AURKC gene in 18 infertile Moroccan patients. They were seen in medical genetic consultation within the framework of the preparatory assessment for medically-assisted procreation. Genomic DNA was extracted from 5 ml of EDTA-blood. The gene AURKC exon 3 was amplified by PCR then sequenced by using the Big-Dye Terminator V3.1 kit and an ABI Prism 310 Genetic Analyzer (Applied Biosystems). All the patients who had a typical phenotype with high rates of large-headed spermatozoa were homozygous for the mutation c.144delC in the AURKC gene. We confirm in this study the research interest of the recurrent mutation c.144delC in the gene AURKC in male infertility with high rates of large-headed spermatozoa. This molecular analysis avoids to many infertile couples unnecessary expenses and succession failures in case of use of medically-assisted procreation (MAP).

Autism spectrum disorder-associated biomarkers for case evaluation and management by clinical geneticists

Autism spectrum disorders (ASDs) are neurodevelopmental disorders, usually diagnosed in early childhood and characterized by varying restrictions in communication and social interaction; as well as by atypical, repetitive behaviors including hyperactivity, poor attention, impulsivity, aggression, self-injury, tantrums and unusual responses to sensory stimuli [1]. Furthermore, common conditions often associated with an ASD diagnosis include gastrointestinal disease and dysbiosis [2], autoimmune disease [3] and mental retardation [4]. Based on a recent survey, ASDs occured in at least one in 150 children born in the USA during the early 1990s [5]. In April of 2008, the American College of Medical Genetics issued clinical practice guidelines recommending that clinical geneticists identify the etiology of ASDs and treat patients with the diagnosis. The work-up includes examining and evaluating the patient, the parents and the siblings, in order to establish a definitive etiology. Depending on the etiology, associated medical risks may be identified, which may lead to screening and potential morbidity prevention in patients and other family members. Specific recurrence risk counseling beyond general multifactorial information can be provided, and targeted testing of at-risk family members can be offered. In a number of cases (e.g., metabolic disorders), targeted therapies may be or become available, strongly justifying a medical genetics consultation for all ASD patients [6]. This article examines recognized, clinically available biomarker testing for the evaluation and treatment of ASDs. It will attempt to explain the clinical significance of the findings and, where possible, explore potential treatment options.

A Genetic Services Practice Model: Advanced Practice Nurse and Genetic Counselor Team

Genomics or the interaction of one's genes and the environment is changing our concept of health and disease, available therapies, use of genetic testing, and related societal ramifications. As genomics integrates into all aspects of health care, the demand will increase for meaningful interpretation and application of the new genetic information. To meet this demand, new service delivery models must be considered. Nurse practitioners and genetic counselors are midlevel providers that can, together, provide clinical evaluation, case management, follow-up, and the genetic counseling aspects of a comprehensive medical genetics consultation. Midlevel providers working with a medical geneticist can expand access to this level of expertise, thereby reaching more patients and consumers. This nurse practitioner–genetic counselor practice model is described in the context of a rural setting.

Molecular genetic basis of tapetoretinal degeneration

The review on problem tapetoretinal degeneration (TD) which represents serious enough and incurable disease revealed with frequency 1 : 3500-5000 in general population is presented. The most often reason of occurrence TD are mutations in RHO, RDS and RPE65 genes. The precise interrelation of pigmentary degenerations of a retina and mutations in genes RHO, RDS and RPE65 will allow to develop approaches of DNA--diagnostics of hereditary dystrophies of a retina so frequently meeting in clinical practice of the ordinary ophthalmologist, and also to pass at medical genetics consultation from probability estimations of risk of disease to unequivocal. Also the molecular analysis of genes changes in the providing correct functioning of photoreceptors and pigmentary epithelium of a retina and determining pathological changes at TD, will allow to approach to understanding of the physiological and pathological processes proceeding in a retina and by that will serve becoming and development pathogenic to caused therapy TD closer.

Establishment and Management of Medical Genetic Clinic Based on Genetic Testing Network

With the progress of the Human Genome Project, genetic testing has become widely available and useful for the confirmation and treatment planning of various conditions. Additionally, the need for genetic counseling and consultation service has been increasing. We tried to establish and manage a medical genetic clinic within the department of laboratory medicine by using a genetic testing network. An Inter-laboratory network has been organized between Soonchunhyang University Bucheon Hospital and Samsung Medical Center since January, 2005. As clinical laboratory physicians, we provide medical services ranging from genetic counseling to genetic testing. In this study we surveyed the need and demand for genetic consultation services using a questionnaire. Of the 30 cases that were requested to receive a genetic consultation, 24 were referred to the genetic clinic during the last 11 months. Of these, 18 underwent genetic tests. The request for genetic consultation came mainly from neurology, obstetrics, and pediatrics departments and the distribution of requested disease entities was very heterogeneous. Operating processes became more settled compared to the early period and specific work fields were secured in the genetic consultation services. Over 80% of the respondents replied that a medical genetic clinic was important and that public relations campaign should be continued. Establishment of a medical genetic clinic by using a genetic testing network has led to important changes that the department of laboratory medicine is most suitable for genetic testing and medical genetic consultations and laboratory physicians should be concerned in that field. A medical genetic consultation system based on extensive genetic information and knowledge could enhance opportunities for cooperation in genetic research.