Case Study: Genetic Disease

 

Instructions

 

Case Study: Genetic Disease

 

A 32-year-old woman is concerned about the possibility of being pregnant. During the initial interview, you discover that she missed her usual menstrual cycle over 3 weeks ago. You also notice that her complexion is markedly tan for this time of the year (winter season). You briefly comment on this fact, and she states, “I want to keep my summer tan. So, I keep going to the tanning salon weekly.” She is here today to confirm the pregnancy with her primary care provider, and you are the nurse completing the initial interview. When asked if she has been taking a folic acid supplement, she states that she had “no concerns of pregnancy and was not aware of the need to take this medicine.” After she sees her primary care provider, he gives you the plan of care. The plan is to have a maternal serum marker test drawn today and recommend that she start on 600 μg of folic acid daily. In analyzing this case, please answer the following questions:

1. Discuss any teratogenic effect of this individual not taking a folic acid supplement. Explain what effect may occur on the developing fetus, identifying specific risks noted in this case.
2. Explain why the primary care provider included a maternal serum marker test in the plan of care for this individual.
3. Discuss the vulnerability of the fetus based on trimesters and teratogens and the role of the folic acid supplement.
4. Briefly discuss the how UVA and UVB rays contribute to the process of oncogenesis in skin cells.
5. How would you educate this individual on the risk of skin cancer related to increased exposure to UVA/UVB rays? Would you expect the primary care provider to perform a skin assessment during this visit? Why or why not?

 

Case Study: Genetic Disease

 

Genetics and Congenital Disorders: Neoplasia

This module will offer a review of genetics including outlining the importance of nucleic acid, deoxyribonucleic acid (DNA), and ribonucleic acid (RNA). A review of how genetic information flows using terms such as transcription, replication, and translation is also included. Why chromosomes are so important to human development is also covered. Then, this module focuses on the genetic diseases that can occur during defects of transcription, replication, and translation of DNA/RNA. Chromosomal and numeral aberrations, autosomal dominant and recessive diseases, and how our blood types are determined will be covered in this module.

DNA, RNA, and Proteins

DNA, RNA, and proteins are involved with heredity.

Review these terms:

• Nucleic acids
  • Deoxyribonucleic acid (DNA)
  • Ribonucleic acid (RNA)
• Replication
• Mutation
• Transcription
• Translation
• Genetic splicing

Genetics

• Traits caused by single genes are called Mendelian traits, which is a term first coined by Gregor Mendel.
• Each gene occupies a positions along a chromosome, known as a locus.
• Genes at a particular locus can take different forms, called alleles.
• At any given locus in a somatic cell, an individual has two genes, one from each parent.
• A locus that has two or more alleles that occur frequently in a population is called polymorphic (several variants in many forms).
• Genotype: composition of genes at a given locus (your genetic makeup).
• Phenotype: outward appearance of an individual, result of genotype and environment.
• Dominant: allele whose effects are observable
• Recessive: allele whose effects are hidden
• Carrier: individual who has a disease gene but is phenotypically normal
• Pedigree chart: summarizes family relationships and shows which members of a family are affected by a genetic disease.
• Consanguinity: refers to the mating of two related individuals (inbreeding), significant increase in recessive disorders, more prevalent with rarer recessive disorders.

Chromosomes

Chromosomes are composed of protein and DNA. Genetic information is found in the DNA of chromosomes. A gene is a DNA sequence of a single trait.

Sex Determination

Human cells can be categorized into two types: gametes (eggs and sperm) and somatic (body) cells. Normal somatic cells have 23 pairs of chromosomes that contain all the genetic material and instructions for making each cell and tissue of the body; because the chromosomes are in pairs, somatic cells are referred to as diploid (double) cells. Each gamete (sperm and egg cells) has a single set of 23 chromosomes; these haploid (single) cells are fused during fertilization producing diploid cells (McCance & Huether, 2019).

A karyotype is an organized profile of a person’s chromosomes. In a karyotype, chromosomes are arranged and numbered by size, from largest to smallest. In total there are 46 chromosomes, which are arranged in order of decreasing size as 23 matching or homologous pairs. They are divided into autosomes (numbers 1–22) and the sex chromosomes, which are two X chromosomes in a normal female and one X and one Y chromosome in a normal male. Remember that one of each pair of the autosomes (1–22) and one X (23) is of maternal origin, while the other 23 are of paternal origin (McCance & Huether, 2019).

Chromosome Aberrations and Associated Disease

Each of these diseases is a variation of the normal diploid number of chromosomes and each can have a drastic effect on the phenotypical expression of an individual.

Disease associated with chromosomal abnormalities are usually classified as numerical abnormalities or structural aberrations. Numerical aberrations occur when somatic cells contain an abnormal number of chromosomes, whereas structural aberrations occurs when somatic cells contain one or more abnormal chromosomes. They may involve either the sex chromosomes or the autosomes (McCance & Huether, 2019).

Numerical Aberrations

Again, normal somatic cells contain 46 chromosomes and are termed diploid (as the number is twice the haploid number of 23 as found in gametes). A cell with an exact multiple of the haploid number (i.e., an entire set of chromosomes is duplicated once or several times) is called euploid or polyploid. If there is not an exact multiple of an entire set, the condition is called aneuploidy (McCance & Huether, 2019).

In aneuploidy, somatic cells do not contain a multiple of 23 chromosomes due to nondisjunction, thus resulting in a cell with either one extra copy of a chromosome (trisomy) or one with a missing copy of that chromosome (monosomy) (McCance & Huether, 2019).

Each of these conditions is a variation on the normal diploid number of chromosomes. As you would expect, each of these can have drastic effects on phenotypic expression (McCance & Huether, 2019).

An example of aneuploidy is Down syndrome, or Trisomy 21. This disorder results when nondisjunction of chromosome 21 occurs at meiosis, producing one gamete with an extra chromosome 21 (N+1 = 24) so the child’s chromosome number is 47 rather than 46. The parents of such children have a normal karyotype and are normal in all respects. Maternal age is a strong risk factor for increased incidence of Down syndrome (McCance & Huether, 2019).

A number of abnormal karyotypes involving the sex chromosomes, ranging from 45 (X) to 49 (XXXXY), are compatible with life. Two of the more common disorders are Klinefelter syndrome (47, XYY males) and Turner syndrome (45, X females) (McCance & Huether, 2019).

Klinefelter syndrome is best defined as male hypogonadism that develops when there are at least two X chromosomes and one or more Y chromosomes as shown in the below karyotype. Most patients are 47, XXY. This karyotype results from nondisjunction of the sex chromosomes during meiosis. The extra X chromosome may be of either maternal or paternal origin (McCance & Huether, 2019).

Turner syndrome, characterized by primary hypogonadism in phenotypic females, results from partial or complete monosomy of the short arm of the X chromosome. In approximately 57% of patients, the entire X chromosome is missing, resulting in a 45, X karyotype. These patients are the most severely affected, and the diagnosis can often be made at birth or early in childhood. You will find more information about the clinical characteristics of Turner and Klinefelter syndromes in the textbook (McCance & Huether, 2019).

Transmission of Genetic Diseases

Single gene disorders (Mendelian disorders) are due to mutations in one or both members of a pair of autosomal genes or to mutations in genes on the X or Y chromosomes (sex-linked inheritance). These disorders show characteristics patterns of inheritance in family pedigrees (McCance & Huether, 2019).

Autosomal Dominant Inheritance

One parent is usually affected by the diseases caused by autosomal dominant disorders that are manifested in the heterozygous state.

• All affected individuals should have an affected parent.
• Both sexes exhibit the trait in equal proportion.
• Approximately 50% of the offspring of an affected will be affected.
• Unaffected persons do not transmit the condition.
• Each birth is an independent event.

Examples of autosomal dominant diseases are Huntington’s disease, familial hypercholesterolemia (FH), achondroplastic dysplasia, and neurofibromatosis. The condition of FH is due to a single mutant gene on the short arm of chromosome 19. Thus, each of the affected persons is a heterozygote. If this affected person marries an unaffected person (normal homozygote), the expected ratio of affected to unaffected offspring is 50%.

A number of variations are seen in autosomal dominant diseases. These include:

• Recurrence Risk: “What is the chance that our child will have this disease?” Each birth is an independent event, much like a coin toss.
• Penetrance is the percent of those with a specific genotype that exhibit an expected phenotype. Some people may not exhibit the disease phenotype at all but may pass it on to the next generation.
• Expressivity is the extent of variation in the phenotype associated with a particular genotype that allows great variability in severity of the diseases.
• Age-dependent penetrance: One of the key features of some diseases is that symptoms are not usually seen until age 40 years or later. With Huntington’s disease, the effects of this disease are not seen until age 40, after the childbearing years. This delayed age of onset allows the disease to be passed on (McCance & Huether, 2019).

Autosomal Recessive Inheritance

In this mode of inheritance, the person must have two copies of the abnormal allele to manifest the disease. Carriers (heterozygotes, who have one abnormal allele and one normal allele) do not display the phenotype because the normal allele is dominant. For instance:

• Both sexes exhibit the trait in equal proportion.
• Usually there is no previous family history.
• The disease may be seen in siblings, but not in parents.
• On average, 25% of the offspring of carrier parents will be affected.

The following features outline the differences between autosomal dominant disease and autosomal recessive disorders:

• The expression of the defect tends to be more uniform.
• Complete penetrance is common.
• Onset is frequently early in life and both sexes exhibit the trait in equal proportion.
• Because the parent is an asymptomatic heterozygote, several generations may pass before the descendants an individual caring the recessive deficit meets (i.e., mates) with other heterozygotes and has children who are affected by the recessive trait.

Examples of autosomal recessive disorders are PKU, sickle cell disease, and cystic fibrosis.

For a parent with sickle cell disease, each child must receive a mutant allele. If a parent with sickle cell disease marries a homozygous normal person (HbA/HbA), then their children will be unaffected heterozygotes (HbA/HbS). If, by chance, a person with sickle cell disease marries a heterozygote, then there will be 50% chance on average that each child will be affected. If both parents are unaffected heterozygotes, then 25% of their children are at risk of having sickle cell disease (McCance & Huether, 2019).

X-Linked Inheritance

X-linked inheritance is caused by genes located on the X chromosomes. The Lyon hypothesis states that one member of the pair of X chromosomes in every female cell is inactivated during early development. This explains why gene products coded by the X chromosome are present in equal amounts in males and females, even though males have only one X. Which of the two X chromosomes gets turned off in each of the early-developing female cells is purely a random event except where one of the X chromosomes is abnormal.

In contrast to females, males have only one X chromosome and hence only one copy of X-linked genes. Each daughter must receive her father’s X chromosome, and each son must receive his father’s Y chromosome. Hence, a father cannot transmit X-linked genes to their sons. X-linked dominant disorders are fairly rare. More common are X-linked recessive disorders. This means that in females, the alleles must be homozygous for the disease to be transmitted. If a female is heterozygous for an X-linked trait, the normal allele counteracts the effects of the diseased allele and the female is phenotypically normal. Common examples of X-linked recessive diseases are hemophilia and color blindness, both seen primarily in men (McCance & Huether, 2019).

Characteristics of X-linked recessive inheritance: The trait is more frequently seen in males. The trait is never transmitted from father to son since the father passes the Y chromosome to his son. The gene may be transmitted through a series of carrier females. The trait may look like it “skipped generations” (McCance & Huether, 2019).

Transmission of Genetic Diseases

Single gene disorders (Mendelian disorders) are due to mutations in one or both members of a pair of autosomal genes or to mutations in genes on the X or Y chromosomes (sex-linked inheritance). These disorders show characteristic patterns of inheritance in family pedigrees (McCance & Huether, 2019).

Blood Types

There may be more than one allele for a trait present in a population. The concept that some characteristics are determined by three or more different alleles is called multiple alleles. However, an individual has only a maximum of two of the alleles for the characteristic. An example of a multiple allele trait is the ABO blood type, which has three alleles in the population: allele A, allele B, and allele O (McCance & Huether, 2019).

Genetic Inheritance Patterns

Alleles A and B show codominance when they are together in the same individual, but both are dominant to the O allele. These three alleles can be combined as pairs in six different ways, resulting in four different phenotypes (McCance & Huether, 2019).

Neoplasia

Theories of Carcinogenesis

Recent studies suggest that the formation of cancer is not a “one-hit” event. Instead, there is an evolution of changes form the normal cell to the invasive metastasizing cell. It is believed that cancers have a monoclonal origin (that is, the cancer starts from one normal cell) and that many cellular accidents are required to cause cancer. It is estimated that three to seven independent random events occur that change the normal originating cell into a cancer cell. Certain forms of cancer-causing genes (oncogenes) may be present in an individual. These genes encode for factors that stimulate cell growth and may be balanced by tumor suppressor genes which encode for proteins that counteract cell growth (McCance & Huether, 2019).

Point of Mutation

Types of mutated genes:

• Secretion of growth factors (autocrine stimulation)
• Increased growth factor receptors
• Signal from cell-surface receptor is mutated in the “on” position
• Mutation in the ras intracellular-signaling protein
• Inactivation of Rb tumor suppressor
• Activation of protein kinases that drive the cell cycle
• Mutation in the p53 gene

(McCance & Huether, 2019)

Oncogenes are genes that can transform a normal cell into a cancerous cell when inherited or activated by oncogenic viruses. Oncogenes can develop from normal genes (proto-oncogenes) that regulate growth and development by encoding for growth factors and growth factor receptors. These genes may undergo some change that either causes them to produce an abnormal product or disrupt their control so that they are expressed inappropriately and accelerate proliferation.

DNA Oncogenic Viruses

Three DNA viruses are of special interest because they are suspected of causing human cancers: human papillomavirus (HPV), Epstein-Barr virus (EBV), and hepatitis B virus (HBV) (McCance & Huether, 2019).

Viruses implicated in human cancers are called oncogenic viruses. Viruses alter the genome of the infected cell, which then alters the progeny of the host cell. As with RNA, several oncogenic DNA viruses that cause tumors in animals have been identified (McCance & Huether, 2019).

Three-Step Theory of Invasion

Most human cancers appear to arise spontaneously, developing without any known prior exposure to a carcinogenic agent. This suggests that there is a genetic basis. On the other hand, not everyone with identified genetic alterations develops cancer. This has led to the development of the three-step theory of invasion.

We know that human tissue is organized into a series of compartments separated from each other by two types of extracellular matrix (ECM): basement membranes and interstitial connective tissue. Although organized differently, each of these components of ECM is made of collagens, glycoproteins, and proteoglycans. Tumor cells must interact with the ECM at several stages in the metastatic cascade (McCance & Huether, 2019).

A carcinoma must first break the underlying basement membrane, then traverse the interstitial connective tissue, and gain access to circulation by penetrating the vascular basement membrane. Invasion of the ECM is an active process that can be viewed as three steps:

1. The first step, attachment of tumor cells to ECM proteins such as laminin and fibronectin, is important for invasion and metastasis.
2. The second step in invasion is local degradation of the basement membrane and interstitial connective tissue. Tumor cells secrete proteolytic enzymes themselves or induce the host cells to secrete proteases.
3. The final step of invasion is migration (locomotion), propelling tumor cells through the degraded basement membranes and zones of matrix proteolysis (McCance & Huether, 2019).

Reference

McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed.). Elsevier, Inc.

 

Case Study: Genetic Disease

 

How to Format your Paper

Case Study: Genetic Disease

Title of Paper

This section is for the introductory paragraph. Do not copy and paste the case scenario as it will immensely increase your Turnitin similarity score. This section should be only 2-5 sentences in length.

Pathology

Introduction and Identification

Introduce the specific themes and main elements of case study. Identify specific pathology. This is not a copy and paste of the case study scenario. Use evidence-based research.

Explanation and Plan of Care

Explain the pathological condition. Specifically discuss a plan of care for the individual in the case study (i.e. Teach the wife the importance of protein in the diet, turning, etc.). Use evidence-based research in both areas.

Discussion Questions

Response to Question #1

Thoroughly address all the prompts (The three questions in the case study: Distinguish, Discuss, Explain) using evidence-based research to support your claim.

Response to Question #2

Thoroughly address all the prompts (The three questions in the case study: Distinguish, Discuss, Explain) using evidence-based research to support your claim.

Response to Question #3

Thoroughly address all the prompts (The three questions in the case study: Distinguish, Discuss, Explain) using evidence-based research to support your claim.

Patient-care Technologies

Explain the role of patient-care technologies in caring for the individual in this case study (What current technology might help the wife, the patient or the health care team in this particular case study?) Use evidence-based research to support your discussion.

 

Case Study: Genetic Disease

 

Reading and Resources

• This brief article discusses a community effort at controlling genetic diseases in underserved Amish and Mennonite communities in PA, a vulnerable population. The article details the efforts of the group of the last 20+ years in using a combination of funding, current technology, and community effort to monitor children with specific genetic diseases in this vulnerable population.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477994/?tool=pmcentrez

• This website gives you the definition of skin cancer from the National Cancer Institute, statics of skin cancer, and other important details concerning this type of cancer.

https://www.cancer.gov/types/skin

 

Case Study: Genetic Disease

 

 

CITATION