A 6-day-old, genotypically normal (46,XX) female patient shows symptoms of hypoglycemia (low blood glucose) and hypotonia (decreased muscle tone). Physical examination reveals abnormal development of the external genitalia, and laboratory studies show elevated urinary sodium content, increased serum levels of potassium, and abnormal serum concentration of several steroid hormones. The patient is diagnosed with 21-hydroxylase deficiency, the most common type of congenital adrenal hyperplasia (CAH).CAH refers to a group of autosomal recessive diseases, each associated with defective production of one or more steroid hormones by the adrenal glands, two crescent-shaped glands located above each kidney in the abdominal cavity. It has been reported that unequal crossing over involving chromosome 6 can result in CAH. More than 90% of CAH diagnoses are associated with a deficiency of 21-hydroxylase, an enzyme encoded by the CYP21A2 gene on chromosome 6.Normally, 21-hydroxylase catalyzes chemical reactions involved in the synthesis of aldosterone and cortisol, the principal mineralocorticoid and glucocorticoid hormones, respectively. As a result, patients with 21-hydroxylase deficiency exhibit diminished serum levels of aldosterone and cortisol. However, synthesis and secretion of the sex hormone testosterone is excessive. Among the normal actions of glucocorticoids are metabolic and anti-inflammatory effects, and glucocorticoid deficiency disrupts the negative feedback loop linking the brain to the adrenal gland. Glucocorticoid deficiency can lead to hyperplasia (increased cell proliferation) of adrenal tissue.The patient's 21-hydroxylase deficiency is treated with regular administration of synthetic steroid hormones. Her condition improves after receiving these medications. Question 30Given that the fusion of male and female gametes results in fertilization, which statement best explains how unequal crossing over during gametogenesis led to 21-hydroxylase deficiency in the fertilized embryo? One of the parental gametes:A.contained an extra copy of chromosome 6.B.contained no copies of chromosome 6.C.experienced an event in which the CYP21A2 gene was duplicated.D.underwent an event in which the CYP21A2 gene was deleted.
Question
A 6-day-old, genotypically normal (46,XX) female patient shows symptoms of hypoglycemia (low blood glucose) and hypotonia (decreased muscle tone). Physical examination reveals abnormal development of the external genitalia, and laboratory studies show elevated urinary sodium content, increased serum levels of potassium, and abnormal serum concentration of several steroid hormones. The patient is diagnosed with 21-hydroxylase deficiency, the most common type of congenital adrenal hyperplasia (CAH).CAH refers to a group of autosomal recessive diseases, each associated with defective production of one or more steroid hormones by the adrenal glands, two crescent-shaped glands located above each kidney in the abdominal cavity. It has been reported that unequal crossing over involving chromosome 6 can result in CAH. More than 90% of CAH diagnoses are associated with a deficiency of 21-hydroxylase, an enzyme encoded by the CYP21A2 gene on chromosome 6.Normally, 21-hydroxylase catalyzes chemical reactions involved in the synthesis of aldosterone and cortisol, the principal mineralocorticoid and glucocorticoid hormones, respectively. As a result, patients with 21-hydroxylase deficiency exhibit diminished serum levels of aldosterone and cortisol. However, synthesis and secretion of the sex hormone testosterone is excessive. Among the normal actions of glucocorticoids are metabolic and anti-inflammatory effects, and glucocorticoid deficiency disrupts the negative feedback loop linking the brain to the adrenal gland. Glucocorticoid deficiency can lead to hyperplasia (increased cell proliferation) of adrenal tissue.The patient's 21-hydroxylase deficiency is treated with regular administration of synthetic steroid hormones. Her condition improves after receiving these medications. Question 30Given that the fusion of male and female gametes results in fertilization, which statement best explains how unequal crossing over during gametogenesis led to 21-hydroxylase deficiency in the fertilized embryo? One of the parental gametes:A.contained an extra copy of chromosome 6.B.contained no copies of chromosome 6.C.experienced an event in which the CYP21A2 gene was duplicated.D.underwent an event in which the CYP21A2 gene was deleted.
Solution
The best explanation for how unequal crossing over during gametogenesis led to 21-hydroxylase deficiency in the fertilized embryo is that one of the parental gametes underwent an event in which the CYP21A2 gene was deleted (Option D).
Here's why:
Unequal crossing over is a process that occurs during meiosis, the type of cell division that produces gametes (sperm and egg cells). During this process, homologous chromosomes (pairs of chromosomes that are the same size, shape, and carry the same genes) line up and exchange segments. However, if this exchange is not perfectly equal, it can result in one chromosome gaining a segment (duplication) and the other losing a segment (deletion).
In the case of 21-hydroxylase deficiency, the CYP21A2 gene on chromosome 6, which encodes the 21-hydroxylase enzyme, is affected. If this gene is deleted due to unequal crossing over, the resulting gamete will lack the ability to produce the 21-hydroxylase enzyme. If this gamete is involved in fertilization, the resulting embryo will inherit this deficiency, leading to the symptoms of 21-hydroxylase deficiency as described in the question.
Therefore, the statement that best explains the situation is that one of the parental gametes underwent an event in which the CYP21A2 gene was deleted.
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