Mode of Inheritance and Clinical Characteristics of Hereditary Night Blindness

doi:10.21203/rs.3.rs-7499901/v1

Background: Reduced vision in low light or at night is a symptom of night blindness, also known as nyctalopia, which occurs when the eye does not adjust quickly enough from bright to dark environments. It is a sign of a wide variety of inherited and congenital retinal disorders and a consequence of vitamin A insufficiency. Night blindness can be present at birth, brought on by an injury, or result from poor nutrition. It is a lack of adjustment to the dark.

Objective: The current study was designed to measure the prevalence, mode of inheritance and some clinical aspects of night blindness disorders in some selected families of district OKARA, Punjab Pakistan.

Methods: Initially, the data was collected through a survey by visiting schools, colleges and hospitals to point out the affected families with night blindness disorder. After selecting affected families, consent from those families was taken for the interview. Data for prevalence, mode of inheritance and clinical symptoms were gathered from those families during interviews. FIVE families with cousin marriages were selected for pedigrees.

Results: Recessive, dominant and sex-linked mode of inheritance was observed. In families, OKR 1, OKR 2, OKR 3, OKR 4 and OKR 5, the percentage of family members associated with night blindness was 20.45%, 53.33%, 13.88%, 12.76%, and 6.25% respectively. It was further noted that most males were affected in all families.

Conclusion: The observed inheritance pattern of night blindness among these families was autosomal dominant, autosomal recessive and X-linked.

Epigenetics & Genomics

Medical Genetics

Night Blindness

Nyctalopia

Inherited Retinal Disorders

Vitamin A Insufficiency

Prevalence

Mode of Inheritance

Autosomal Dominant

Autosomal Recessive

X-linked Inheritance

Family Pedigrees

The majority of genetic disorders can be traced back to either an insufficient amount of genetic material or mutations (dangerous modifications to genes also known as pathogenic variations) (1). Your genes, which are made up of DNA (deoxyribonucleic acid), include instructions for how your cells should operate and the characteristics that make you unique. DNA mistakes, known as mutations, can alter the genetic material. Reduced vision in low light or at night is a symptom of night blindness, also known as nyctalopia, which occurs when the eye does not adjust quickly enough from bright to dark environments (2). It is a sign of a wide variety of inherited and congenital retinal disorders and a consequence of vitamin A insufficiency. When you have night blindness, it is hard, if not impossible, to see in dim conditions. Night blindness from birth, with or without myopia (nearsightedness), is a persistent genetic condition that can be inherited in a dominant, recessive, or sex-linked pattern (3). Retinitis pigmentosa is an inherited disorder that causes gradual vision loss due to the death of rod cells (visual receptors important for seeing in dim light), which can manifest as sudden onset night blindness in children or teenagers. A shortage in vitamin A is one of the leading causes of retinitis pigmentosa, a kind of macular degeneration. Progressive degeneration of photoreceptors and the retinal pigment epithelium (RPE) causes RP symptoms such as night blindness, tunnel vision, and a slow loss of central vision. Florent Cunier, in 1838, was the first to describe congenital stationary night blindness (CSNB). Cunier researched the family tree of a 23-year-old child with night blindness and found 56 members of the family who had also been affected by night blindness going back 11 generations to a man named Jean Nougaret.

The "Ebers Papyrus" No. 351 from around 1500 B.C. describes night blindness in ancient Egypt; this information was likely gleaned from much older medical texts dating back to 2500 B.C. To address this condition, the Egyptians resorted to injecting the juice derived from compressed liver directly into the eye. However, modern studies indicate that the cornea's limited ability to absorb vitamin A from liver extract would not be sufficient to effectively alleviate night blindness (4). Night blindness is discussed in the Assyrian medical books from around 700 B.C. They believed the moon's beams caused the disease and could be treated by rubbing the ass's liver on the affected eyes. Nettleship continued Cunier's work in the 20th century and confirmed that the disease is strongly heritable but does not worsen over time (5). Mutations in the RHO, GNAT1, or PDE6B genes cause an autosomal dominant form of stationary night blindness (6). Mutations in the genes for RHO, GNAT1, and PDE6B alter the normal signaling in rod cells. The inability of the rods to send reliable signals to the brain results in impaired vision in dim light. These genes are essential for healthy vision, especially in dim light. The World Health Organization estimates that 254 million children around the world are deficient in vitamin A (7). This disorder accounts for the vast majority of cases of blindness in young children. About half of these kids are born in South and Southeast Asian countries. Nyctalopia, retinopathy, xerophthalmia, bitot spots, keratomalacia, conjunctival and corneal xerosis, conjunctival xerosis, and corneal xerosis are all associated clinical ocular disorders. Children under the age of six in Pakistan's North West Frontier Province (NWFP) are at increased risk for developing night blindness and/or color blindness. About 20% of Karachi's elementary and secondary school students have one of these conditions. Children in the NWFP are at a higher risk for night blindness and color blindness if they are younger than 6 years old. (8). According to statistics from 2003, there are around 1,140,000 (962,000–1,330,000) blind adults in Pakistan. In Pakistan, cataracts account for over half (48.1%) of all causes of blindness.

The objective of current study was to provide information on night blindness in the Okara area of Punjab, Pakistan. The prevalence of such genetic disorders in Pakistan is also an important aspect of the present study. This study was design to record the mode of inheritance, prevalence and the clinical investigation of night blindness disorder in families of district OKARA.

Study Area

The current study was conducted in Okara (derived from Okaan, which is the name of a type of tree) is a city in Punjab, Pakistan. It is the 23^rd largest city of Pakistan by population. The city is located southwest of the city of Lahore and Faisalabad is 100 km bypassing away Ravi River. It is known for its agriculture-based economy and cotton mills. The nearest major city to Okara is Sahiwal, which was formerly known as Montgomery. Pakistan military dairy farms, known for their cheese, are situated in Okara. Wheat, cotton, tobacco, legumes, potato, and oil seeds are the main crops.

Research Design

Mix method research design (epidemiological study and clinical investigation) was applied in the current study.

Study Population

The mixed method study was carried out on the general population with night blindness disorder in the district OKARA, province of Punjab, Pakistan.

Sample Collection

Both rural and urban areas of district Okara was visited to find out the families with disorders. After detailed visits, five families were selected for study and to construct the pedigree. The pictures of affected individuals were also taken with the consent of each family. The samples were collected from five different families using simple and direct questions. The university's ethical committee granted permission to conduct the current research (Table 1).

Table 1: Sampling Sites

Family	Name of Area	Geographical coordinates
OKARA 1	Chak No. 9/4-L, OKARA	30.7617° N, 73.4283° E
OKARA 2	Raza block, Street # 01, District OKARA	73° 27' 33.8256'' E
OKARA 3	Chak No. 28/4-L, Thana Shahbore, OKARA	30.7059° N, 73.3829° E
OKARA 4	Chak No. 19/1-R, OKARA	30.8920° N, 73.4997° E
OKARA 5	Basti Abdul Sattar, Bangla Gogera, OKARA	28° 41' 45" North, 70° 33' 20" E

Data Analysis

Clinical symptoms and cousin marriages are analyzed that there are how many first cousin marriages and second cousin marriages. Male and female are analyzed, either male have more chances of night blindness than female. Rural and urbans areas are analyzed and then we check the epidemiology.

Pedigree Analysis

Five families were selected for pedigree analysis and all families were detailed interviewed on the spot. The frequency and the mutation of night blindness disorder in each family was recorded through pedigree analysis.

Statistical Analysis

Statistics analysis is performed to check the prevalence and percentage of families of night blindness disorder. Data were analyzed by using MS office software, using descriptive statistics to find mean, percentage and prevalence rate of the diseases.

This study was to investigate the prevalence and clinical features of night blindness among some selected families of district OKARA.

Demographic Characters

In the current study, total of 5 families participated. These five families were comprising of total 190 members. On which, there are 103 males and 87 females. Among all individuals, 123 members are alive and 67 individuals were dead. 15 individuals were residents of urban and 175 were residents of rural areas (Table 2).

Table 2: Demographic characters of respondents in the studied population

Participant Characteristics	Frequency	Percentage %
Gender
Male	103	54.21%
Female	87	45.78%
Age
≤25 years	38	20%
26-35 years	41	21.57%
36-45 years	71	37.36%
>45 years	40	21.05%
Residence/ Locality
Urban	15	7.89%
Rural	175	92.10%
Marriage
Consanguineous	6	18.18%
Non-consanguineous	27	81.81%
Alive
Male	67	54.47%
Female	56	45.52%
Death
Male	36	53.73%
Female	31	46.26%

Prevalence of Night Blindness

The present study was planned to record the mode of inheritance of night blindness in selected families of the OKARA, Punjab Pakistan. Five families with night blindness were selected for the detailed study. The persons having night blindness disorder were identified. The prevalence of this genetic disorder was 16.31% in the studied families. The prevalence was recorded by number of affected men out of total number of members of the family. Out of 190 members, 31 were affected with hypotrichosis (Table 3).

Table 3: Prevalence of Night blindness

Family	Total member	Affected	Percentage%
OKARA 1	44	9	20.45%
OKARA 2	15	8	53.33%
OKARA 3	36	5	13.88%
OKARA 4	47	6	12.76%
OKARA 5	48	3	6.25%
Total	190	31	16.31%

The prevalence of night blindness was different in different families. In family, OKA 1 was observed 20.45%, OKA 2 was 53.33%, OKA 3 was 13.88%, OKA 4 was 12.76%, OKA 5 was 6.25%, in affected members. The prevalence rate of night blindness was higher in males (74.19%) while it was a very lower in females (25.80%) (Table 4).

Table 4: Number of Males and Females associated with Night Blindness

Family	Total associated with Night Blindness	Number of Males	Number of Females
OKARA 1	9	4	5
OKARA 2	8	6	2
OKARA 3	5	4	1
OKARA 4	6	6	0
OKARA 5	3	3	0
Total	31	23	8

Description of Family OKA 1

Family 1 belongs to district OKARA, province of Punjab Pakistan. Affected members were present in four generations. Most parents of this family have non- Consanguineous marriage. A total nine members (4 males and 5 female) are found to affect by this genetic disorder. The pedigree sketch showed the five generations consisting of 44 family members with 1 affected member in 1^st generation, 2 affected members in 2^ndgeneration, 3 affected members in 4^th generation and 3 affected members in 5^th generation. According to clinical point of view, symptoms of these 6 alive affected persons are same. They cannot see in night time properly. Their vision at day time is too much low now. At night time, they have difficulty to walk at any place and they walk with any support like stick or with any person. Clinical examination of affected members whose data can be calculated shows that night blindness autosomal recessive type is present. The pedigree of the family is shown in Fig. 1.

Description of Family OKA 2

Family 2 belongs to District OKARA, province of PUNJAB, PAKISTAN. Affected members were present in all three generations. Parents of this family are not-sibling. Parents of this family have non- Consanguineous marriage. A total eight members (6 males and 2 females) are found to affect by this genetic disorder. The pedigree sketch showed the three generations consisting of 15 family members with 1 affected member in 1^st generation, 3 affected members in 2^nd generation and 4 affected members in 3^rd generation. According to clinical point of view, symptoms of these 8 affected persons are same. They cannot see in night time properly. They can see at day time at the age of 10 to 12 years but on later years their eye sight weakened too much. At night time, they walk with any support like stick or with any person. In pedigree sketch, two affected members in 3^rd generation cannot walk by self. Clinical examination of affected members whose data can be calculated shows that night blindness dominant type is present. The pedigree of this family is shown in Fig. 2.

Description of Family OKA 3

Family 3 belongs to District OKARA, province of Punjab, Pakistan. Affected members were present in one generation only. Parents of this family are not related to each other. A total of five members (4 males and 1 female) are found to affect by this genetic disorder. The pedigree sketch showed the four generations consisting of 36 family members with 5 affected members in 4^th generation. According to clinical point of view, symptoms of these 5 affected persons are same. At day time, when there is proper sunlight when they see towards sunlight, their eyes are completely closed and eyes cannot open in daylight and their eyes watered. They cannot see in night time properly. Some members can see properly at day time at the age of 10 to 12 years but on later years their eye sight weakened too much. At night time, they walk with any support like stick or walk with any person. Clinical examination of affected members whose data can be calculated shows that night blindness Autosomal dominant type is present. The pedigree of this family is shown in Fig. 3.

Description of Family OKA 4

Family 4 belongs to district OKARA, province of PUNJAB, PAKISTAN. Affected members were present in two generations. Some parents of this family are related to each other (relatives) but others are not related. A total of six 6 members 6 males only are found to affect by this genetic disorder. The pedigree sketch showed the five generations consisting of 47 family members with 6 affected members, 3 affected members in 4^th generation and 3 affected members in 5^th generation. According to clinical point of view, symptoms of these 6 affected persons are same. At day time, when there is proper sunlight, they can see properly in day light but not see far objects clearly. They cannot see in night time properly. They see any object shade only. If they don’t see towards light, then their eyesight is well and they can clearly differentiate between all colors. At night time, they have difficulty to walk at any place. Clinical examination of affected members whose data can be calculated shows that night blindness Sex-linked dominant type is present. The pedigree of this family is shown in Fig. 4.

Description of Family OKA 5

Family 5 belongs to BANGLA GOGERA, Tehsil and District OKARA province of PUNJAB, PAKISTAN. Affected members were present in one generation only. Parents of this family are related to each other (relatives). A total of three 3 members, 3 males are found to affect by this genetic disorder. The pedigree sketch showed the 4 generations consisting of 48 family members with 3 affected members in 4^th generation. According to clinical point of view, symptoms of these 3 affected persons are same. At day time, when there is proper sunlight, they can see properly in day light but not see far objects clearly and seen like blur. When there is night time, they cannot see properly. This defect is present from birth time. Their vision at day time is too much low now. At night time, they have difficulty to walk at any place. Clinical examination of affected members whose data can be calculated shows that night blindness Sex-linked type is present. The pedigree of this family is shown in Fig. 5.

From a physiological standpoint, the development of retinal pigments is essential. Congenital night blindness is a physical condition that can affect humans, dogs, cats, and other animals. (9) The absence of retinal pigments is characteristic of this disorder. Congenital stationary, x-linked recessive, and dominant are three of the many subtypes of this disorder. (10) Night blindness is a catch-all phrase for a group of ophthalmological conditions that diminish one's vision in dim light, or scotoma. (11) This study was designed to study the prevalence rate of night blindness disorder among some selected families of district OKARA. Results of the current study showed that the prevalence rate of night blindness among selected families was 16.31%. The reason behind the prevalence rate of night blindness among selected families was due to consanguineous and non- consanguineous marriages. Among 5 families, there were 33 marriages, of which 6 (18.18%) marriages are consanguineous and 27 (81.81%) are non-consanguineous. Of 6 consanguineous marriages, 3 consanguineous marriages are such marriages which inherited their offspring with night blindness disorder and only 2 non-consanguineous marriage have night blindness disorder. This study concluded that the prevalence rate of night blindness varies in each family. The prevalence rate among family OKR 1 was 20.45%, family OKR 2 was 53.33% Family OKR 3 was 13.88%, family OKR 4 was 12.76%, and Family OKR 5 was 6.25% respectively.

According to the findings of our research, marriage inside a family increases the likelihood of contracting an illness when compared to marriage between unrelated individuals. Consanguineous marriages are connected with an high risk for congenital abnormalities and autosomal recessive illnesses with some instances of higher postnatal mortality in the kids of first-cousin couples as a consequence of this increased risk (12). The findings of our research indicate a clear association between consanguineous marriages and night blindness disorder in certain families. Consanguinity increases the likelihood of inheriting recessive genetic disorders including those affecting cognitive function (13). The higher incidence of night blindness observed in the families studied suggests a potential genetic basis for this condition. Consanguinity leads to an increased risk of offspring inheriting homozygous recessive alleles, which can result in the expression of deleterious genetic mutations associated with night blindness disorder (13).

It is important to note that not all individuals from consanguineous marriages will experience night blindness. The expression of genetic disorders is influenced by various factors, including the specific recessive alleles carried by the parents, the presence of additional genetic modifiers and the complex interplay between genetics and environmental influences. (14) By the pedigree analysis of these families, it is indicated that the mode of inheritance of night blindness was X-linked, dominant and recessive.

In conclusion, the night blindness prevailed in the families up to generations due to cousin marriages. The age of onset in these families was 25 years or above. Males were more affected than females.

Conflict of Interest

Authors declare no conflict of interest.

Authors Contribution

M. Kashif Aslam: Data collection, Formal analysis, Review, and writing of the initial draft. Faisal Ali: Formal analysis, Review, and writing of the initial draft. Azhar Iqbal: Material and Methods, and Review and writing of the initial draft. Aleezah Shaukat-ul-Hassan: Formal analysis. M. Saleem Khan: Conceptualization, investigation, and supervision. Sidra Abbas: Review and writing of final version of the manuscript. All authors reviewed the final version of the manuscript and approved it for publication.

Funding Note:

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Acknowledgment

The authors would like to acknowledge the support and resources provided by the Department of Biotechnology, University of Okara.

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The authors declare no competing interests.

Mode of Inheritance and Clinical Characteristics of Hereditary Night Blindness

Status:

Version 1

Abstract

Figures

Introduction

Materials and Methods

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

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