Question

For decades scientists have been perplexed by different circumstances surrounding families with rare, early-onset auditory neuropathy (deafness). In some families, parents and grandparents of the proband have normal hearing, while in other families, a number of affected (deaf) family members are scattered throughout the pedigree, appearing in every generation. Assuming a genetic cause for each case, offer a reasonable explanation for the genetic origin of such deafness in the two types of families.

Short answer

Answer: In families where parents and grandparents of the proband have normal hearing, a recessive inheritance pattern for deafness is likely. In families where deaf family members are scattered throughout the pedigree in every generation, a dominant inheritance pattern for deafness is more plausible.

Step-by-step solution

Case 1: Parents and grandparents of the proband have normal hearing

Since the parents and grandparents of the proband have normal hearing and the proband is affected, this suggests that the genetic cause of deafness in this situation might be due to a recessive gene. In a recessive inheritance pattern, an individual must inherit two copies of the mutated gene (one from each parent) to express the phenotype. If both parents are carriers of the mutation (heterozygous for the gene), they can have a child with the deafness phenotype, even though they themselves have normal hearing. In this case, each offspring has a 25% chance of inheriting the deafness phenotype, a 50% chance of being a carrier like their parents, and a 25% chance of having normal hearing without carrying the mutation.

Case 2: Deaf family members are scattered throughout the pedigree, appearing in every generation

In the second case, where deaf members are scattered throughout the pedigree and appear in every generation, this points towards a dominant inheritance pattern for the genetic cause of deafness. In a dominant inheritance pattern, only one copy of the mutated gene is required for an individual to express the phenotype. If a parent has the deafness phenotype due to the dominant mutated gene, the offspring have a 50% chance of inheriting the deafness phenotype and a 50% chance of having normal hearing without carrying the mutation. The presence of affected individuals in every generation supports the dominant inheritance pattern for this case. In conclusion, the genetic origin of deafness in the two types of families can be explained by different modes of inheritance. In the case where parents and grandparents of the proband have normal hearing, a recessive inheritance pattern is likely, while in the case where deaf family members are scattered throughout the pedigree in every generation, a dominant inheritance pattern is more plausible.

Key concepts

Recessive Gene Inheritance

Many genetic conditions, including certain forms of early-onset deafness, are passed down through recessive gene inheritance. This means that an individual must inherit two copies of the mutated gene, one from each parent, in order to exhibit the condition.

Imagine a gene responsible for hearing that comes in two versions (alleles): a normal allele and a mutated allele causing deafness. When a child receives a normal allele from one parent and a mutated allele from the other, they are considered a carrier—they do not show symptoms but can pass the mutated allele to their children. It is only when a child inherits the mutated allele from both parents that recessive genetic conditions manifest.

Parents who are carriers (heterozygous for the gene) can have a child with normal hearing, a carrier child, or a child with the condition. Statistically, each child has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of inheriting two normal alleles.

Dominant Gene Inheritance

In contrast to recessive traits, dominant gene inheritance enables a condition to be passed on even when only one parent contributes the mutated gene. For every gene, if one of the alleles is dominant, the trait that it controls will be expressed in the individual.

The situation with certain types of auditory neuropathy, where the condition appears in every generation of the family, is a classic hallmark of dominant inheritance. Each child of an affected parent has a 50% chance of receiving the dominant mutated allele and, thus, a 50% chance of being affected by the condition. This pattern leads to a vertical pattern in the pedigree, with the trait being present in successive generations and not skipping any, as is often the case with recessive traits.

Understanding dominant inheritance is crucial for predicting the risk of a genetic condition appearing in offspring, especially with conditions that can significantly impact quality of life, such as hearing impairment.

Auditory Neuropathy

Auditory neuropathy is a form of hearing loss where sound enters the ear normally, but because of damage to the inner ear or auditory nerve, the transmission of sound signals to the brain is impaired.

While hearing loss can be caused by many factors, including environmental noise or aging, auditory neuropathy is often genetic in nature. The symptoms can range widely, from mild difficulty with speech comprehension to total deafness, and they may appear at birth or develop later. The management of the condition often involves a combination of strategies, including the use of hearing aids, cochlear implants, and other communication methods such as sign language or lip reading. Knowledge about the genetic basis of auditory neuropathy can guide families in understanding their condition and making informed health decisions.

Pedigree Analysis

To understand how genetic conditions are passed through generations, scientists and genetic counselors use pedigree analysis. This method involves creating a family tree that documents the presence or absence of a trait in family members across generations.

A pedigree chart provides a visual representation to track inheritance patterns and can help determine whether a trait is likely to be dominant or recessive. Symbols such as squares (for males) and circles (for females), shaded to indicate affected individuals, make it possible to visualize how the condition is passing through the family. By analyzing the chart, predictions about the likelihood of future offspring inheriting the condition can be made. This invaluable tool aids in the diagnosis and counseling of families with genetic disorders like auditory neuropathy.

Understanding these patterns provides insights into the risk of transmission to future generations and can guide genetic testing and family planning decisions.