Genetic Counseling and NGS Screening for Recessive LGMD2A Families

Genetic counseling applied to limb–girdle muscular dystrophies (LGMDs) can be very challenging due to their clinical and genetic heterogeneity and the availability of different molecular assays. Genetic counseling should therefore be addressed to select the most suitable approach to increase the diagnostic rate and provide an accurate estimation of recurrence risk. This is particularly true for families with a positive history for recessive LGMD, in which the presence of a known pathogenetic mutation segregating within the family may not be enough to exclude the risk of having affected children without exploring the genetic background of phenotypically unaffected partners. In this work, we presented a family with a positive history for LGMD2A (OMIM #253600, also known as calpainopathy) characterized by compound heterozygosity for two CAPN3 mutations. The genetic specialist suggested the segregation analysis of both mutations within the family as a first-level analysis. Sequentially, next-generation sequencing (NGS) analysis was performed in the partners of healthy carriers to provide an accurate recurrence/reproductive risk estimation considering the genetic background of the couple. Finally, this work highlighted the importance of providing a genetic counseling/testing service even in unaffected individuals with a carrier partner. This approach can support genetic counselors in estimating the reproductive/recurrence risk and eventually, suggesting prenatal testing, early diagnosis or other medical surveillance strategies.

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Genetic Counseling and Diagnostics in Anorectal Malformation

European Journal of Pediatric Surgery ◽

10.1055/s-0041-1740338 ◽

2021 ◽

Vol 31 (06) ◽

pp. 482-491

Author(s):

Carlo Marcelis ◽

Gabriel Dworschak ◽

Ivo de Blaauw ◽

Iris A.L.M. van Rooij

Keyword(s):

Genetic Counseling ◽

Anorectal Malformation ◽

Current Knowledge ◽

Bowel Function ◽

Recurrence Risk ◽

Medical Community ◽

Medical Attention ◽

The Family ◽

Long Term Prognosis

AbstractAnorectal malformation (ARM) is a relatively frequently occurring congenital anomaly of hindgut development with a prevalence of 1 in 3,000 live births. ARM may present as an isolated anomaly, but it can also be associated with other anomalies, sometimes as part of a recognizable syndrome. After birth, much medical attention is given to the treatment and restoring of bowel function in children with ARM. Effort should also be given to studying the etiology of the ARM in these patients. This information is important to both the medical community and the family, because it can help guide treatment and provides information on the long-term prognosis of the patient and recurrence risk in the family.In this article, we will review the current knowledge on the (genetic) etiology of (syndromic) ARM and provide guidelines for (family) history taking and clinical and genetic studies of ARM patients and their families, which is needed to study the causal factors in an ARM patient and for genetic counseling of the families.

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Two Separate Cases: Complex Chromosomal Abnormality Involving Three Chromosomes and Small Supernumerary Marker Chromosome in Patients with Impaired Reproductive Function

Genes ◽

10.3390/genes11121511 ◽

2020 ◽

Vol 11 (12) ◽

pp. 1511

Author(s):

Tatyana V. Karamysheva ◽

Tatyana A. Gayner ◽

Vladimir V. Muzyka ◽

Konstantin E. Orishchenko ◽

Nikolay B. Rubtsov

Keyword(s):

Genetic Counseling ◽

Chromosome Rearrangement ◽

Marker Chromosome ◽

Reproductive Function ◽

Small Supernumerary Marker Chromosome ◽

Comprehensive Chromosome Screening ◽

The Family ◽

Multicolor Banding ◽

The One

For medical genetic counseling, estimating the chance of a child being born with chromosome abnormality is crucially important. Cytogenetic diagnostics of parents with a balanced karyotype are a special case. Such chromosome rearrangements cannot be detected with comprehensive chromosome screening. In the current paper, we consider chromosome diagnostics in two cases of chromosome rearrangement in patients with balanced karyotype and provide the results of a detailed analysis of complex chromosomal rearrangement (CCR) involving three chromosomes and a small supernumerary marker chromosome (sSMC) in a patient with impaired reproductive function. The application of fluorescent in situ hybridization, microdissection, and multicolor banding allows for describing analyzed karyotypes in detail. In the case of a CCR, such as the one described here, the probability of gamete formation with a karyotype, showing a balance of chromosome regions, is extremely low. Recommendation for the family in genetic counseling should take into account the obtained result. In the case of an sSMC, it is critically important to identify the original chromosome from which the sSMC has been derived, even if the euchromatin material is absent. Finally, we present our view on the optimal strategy of identifying and describing sSMCs, namely the production of a microdissectional DNA probe from the sSMC combined with a consequent reverse painting.

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Recurrence risk estimation of acute intermittent porphyria based on analysis of porphobilinogen deaminase activity: A Bayesian approach

American Journal of Medical Genetics ◽

10.1002/ajmg.1320190415 ◽

1984 ◽

Vol 19 (4) ◽

pp. 755-762 ◽

Cited By ~ 17

Author(s):

C. Bonaïti-Pellié ◽

L. Phung ◽

Y. Nordmann

Keyword(s):

Bayesian Approach ◽

Risk Estimation ◽

Acute Intermittent Porphyria ◽

Recurrence Risk ◽

Porphobilinogen Deaminase

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Prenatal Diagnosis

Pediatrics in Review ◽

10.1542/pir.13.9.334 ◽

1992 ◽

Vol 13 (9) ◽

pp. 334-342

Author(s):

John H. DiLiberti ◽

Mark A. Greenstein ◽

Sally Shulman Rosengren

Keyword(s):

Prenatal Diagnosis ◽

Imaging Techniques ◽

Three Dimensional ◽

Prenatal Testing ◽

The Past ◽

Computerized Image Processing ◽

The Family ◽

Family History Assessment ◽

Additional Explanation ◽

Pediatric Disorders

The enormous progress witnessed in the field of prenatal diagnosis during the past two decades is likely to continue into the future. Improved imaging techniques are likely to enhance the resolution of noninvasively obtained fetal images considerably over their current excellent quality. Although this undoubtedly will be true for ultrasonography, the increased speed of magnetic resonance equipment may offer a new realm of imaging possibilities. Computerized image processing, analysis, and three-dimensional reconstructions all should make interpretation of fetal images easier and more understandable to the nonspecialist. Advances in molecular genetics will continue to accelerate, greatly expanding the range and accuracy of prenatal diagnosis. The alert pediatrician who is sensitive to genetic issues may, by early detection of pediatric disorders and careful family history assessment, be in a position to identify families at risk for serious genetic conditions and provide the opportunity to make informed decisions on reproductive options that avert a major tragedy. The pediatrician, working with obstetric colleagues, should be part of a team effort to support families going through prenatal testing. Familiarity with these rapidly changing technologies will make it far easier to support the family needing additional explanation about prenatal diagnosis issues.

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Invasive Prenatal Diagnosis

10.2310/obg.19130 ◽

2020 ◽

Author(s):

Kimberly Zayhowski

Keyword(s):

Genetic Counseling ◽

Prenatal Diagnosis ◽

Genetic Testing ◽

Prenatal Care ◽

Chorionic Villus ◽

Prenatal Testing ◽

Chorionic Villus Sampling ◽

Genetic Tests ◽

Genetic Technologies ◽

Invasive Techniques

Despite recent advances in genetic technologies that are making invasive prenatal diagnosis less common, amniocentesis and chorionic villus sampling (CVS) remain an integral part of prenatal care. A multitude of tests, including a variety of genetic tests, can be performed using samples collected from either procedure. Although invasive testing has limitations, many genetic conditions can only be diagnosed through invasive techniques during pregnancy. Invasive testing continues to assist patients and providers in making informed decisions regarding the care of pregnancies. This review details amniocentesis and chorionic villus sampling with a focus on genetic testing, describing why the tests are performed, the way in which they are performed, and the associated limitations and complications of the procedures. This review 5 figures, 3 tables, and 26 references. Keywords: prenatal diagnosis, amniocentesis, chorionic villus sampling, genetic testing, genetic counseling, invasive prenatal testing, pregnancy, aneuploidy

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Prenatal Genetic Diagnosis for Pediatricians

PEDIATRICS ◽

10.1542/peds.93.6.1010 ◽

1994 ◽

Vol 93 (6) ◽

pp. 1010-1015

Author(s):

Keyword(s):

Decision Making ◽

Genetic Counseling ◽

Prenatal Diagnosis ◽

Diagnostic Tests ◽

Genetic Disorder ◽

Genetic Diagnosis ◽

Decision Making Process ◽

Know How ◽

Prenatal Genetic Diagnosis ◽

The Family

Pediatricians may be called upon to counsel a family in which prenatal diagnosis is being considered or in which there is a fetus with a genetic disorder. In some settings, the pediatrician may be the primary resource for counseling the family. More frequently, counseling may already have been provided by a clinical geneticist and/or obstetrician. However, because of a previous relationship with the family, the pediatrician may be called upon to review this information and to assist the family in the decision-making process. The pediatrician should be familiar with the principles of prenatal genetic diagnosis and know how to apply them to specific problems in genetic counseling, diagnosis, and management in clinical practice. At the same time, pediatricians should be familiar with resources available in their region for obtaining information about whether and how a specific disorder can be diagnosed and when and where to refer patients for prenatal genetic diagnosis. The technology of prenatal diagnosis is changing rapidly, and genetic consultants can assist pediatricians in the appropriate utilization and interpretation of the diagnostic tests that are available.

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Noninvasive Prenatal Testing and Genetic Counseling

Fetal Morph Functional Diagnosis - Comprehensive Gynecology and Obstetrics ◽

10.1007/978-981-15-8171-7_18 ◽

2020 ◽

pp. 239-247

Author(s):

Junko Yotsumoto

Keyword(s):

Genetic Counseling ◽

Prenatal Testing ◽

Noninvasive Prenatal Testing

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Clinical features and genetic analysis of two Chinese families with X-linked ichthyosis

Journal of International Medical Research ◽

10.1177/0300060520962292 ◽

2020 ◽

Vol 48 (10) ◽

pp. 030006052096229

Author(s):

Wanqin Xie ◽

Haiyan Zhou ◽

Lin Zhou ◽

Yun Gong ◽

Jiwu Lin ◽

...

Keyword(s):

Genetic Counseling ◽

Venous Blood ◽

Mendelian Inheritance ◽

Hunan Province ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Entire Body ◽

Chinese Families ◽

The Family ◽

Atypical Phenotype

Objective Recessive X-linked ichthyosis (RXLI) caused by deficiency of the steroid sulfatase gene ( STS) has a reported prevalence of 1/2000 to 1/6000. The present study aimed to characterize the phenotypes and genotypes of two Chinese families with RXLI. Methods The patients were referred to the Family Planning Research Institute of Hunan Province for genetic counseling. Their skin phenotypes were photographed, and venous blood was drawn and used for chromosomal microarray analysis (CMA). Results The skin phenotype of the proband from the first family was characterized by generalized skin dryness and scaling, with noticeable dark brown, polygonal scales on his trunk and extensor surfaces of his extremities. The proband from the second family had an atypical phenotype showing mild skin dryness over his entire body, slight scaling on his abdomen, and small skin fissures on his arms and legs. No mental disability or developmental anomaly was noted in either proband. CMA revealed that both probands carried a 1.4-Mb deletion on chromosome Xp22.31 involving four Online Mendelian Inheritance in Man-listed genes including STS. Conclusions Our findings add knowledge to the genotype and phenotype spectrum of RXLI, which may be helpful in genetic counseling and prenatal diagnosis.

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