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Genetic Diseases In Pakistan

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Last Updated: 02 July 2021

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General | Latest Info

Gene IS unit of inheritance in living organism. These are inhabitants of all information that IS necessary to build up cell, maintain its normal function and pass Down Genetic information onto next generations. According to the Human Genome Project, it is estimated that there are 20 000 to 25 000 protein - coding genes in human DNA. Human DNA IS made up of four nucleic bases, namely Adenine, Cytosine, Thymine and Guanine; abbreviated As, C, T and G respectively. The precise order of As, Cs, Ts and Gs IS critical as it is responsible for the diversity of life on the face of Earth. This sequence dictate, whether an organism IS human or any other specie ie mice, chimps, rice or fruit fly. With the aforementioned functional significance of GENE, we can anticipate drastic effects that could result with alteration in the genetic make - up of organism. A change in the genetic make - up of an organism IS referred to as a mutation. Mutations can cause changes in the structure of protein; expression of protein may either decrease or IS completely lose. One should be well aware of the fact that the functions of most mutations are unknown and result in polymorphisms, while some change GENE function to such an extent that disease IS manifest clinically. Mutations are largely categorized as dominant or recessive. On the other hand, they could be either acquired or inherit. Mutations could predominantly be damaging to cells or organisms as a whole, since any change in sequence of DNA of an organism affects all copies of encoded protein. Thus, it should be kept in view that mutations may or may not spawn changes in the phenotype of an organism. Genetic Disease IS disorder which marks presence of abnormality in genes or chromosomes of an individual. Some genetic disorders ensue at the time of production of germ cells by parent,s while others are consequence of chromosomal abnormalities; to name a few, are insertion, deletion, substitution or frame shift mutations. Genetic disorders are further classified as single GENE disorders, polygenic disorders or mitochondrial disorders. Until date, around 4 000 genetic diseases have been discovered and the number IS likely to increase with advance in human molecular and medical genetics. There IS no recognized human population in which genetic disorders are not know. However, their nature, prevalence and distribution differ in various regions of the world. Nonetheless, Pakistan, with a population size of over 125 million, has managed to rise above the charts and is learning to be a goldmine of genetic disorders due to its unique geography and history;. To mention a few are Down syndrome, Fragile X syndrome, Retinitis Pigmentosa, Gaucher Disease, Congenital Cataract, Phenylketonurea, DeaFNess, Alopecias, Alzheimers, Albinism and Epilepsy. In addition to this, Pakistan IS an amalgam of various ethnicities with exceptional familial and social characteristics. It IS estimated that 700 children are born with genetic disabilities due to cousin marriages every year.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Introduction

Bardet - Biedl syndrome is a complex, heterogeneous, autosomal recessively inherited disorder. 19 causative genes that have been identified thus far 1 encode proteins that function at different sites of primary cilium, non - motile oblong sensory organelle that protrude from the surface of most mammalian cells. Within cilium, BBS proteins are involved in a wide variety of processes ranging from regulation of intraflagellar transport to chaperonin and GTPase activity. On retinal Disease information database, RetNet: Summaries of genes and loci causing retinal diseases, more than 20 genes are enlisted as causative of BBS. The BBS phenotype is multi - systemic, Its primary features are blindness, renal dysfunction, intellectual disability, polydactyly, obesity and hypogonadism 2. In addition, secondary characteristics include hepatic malfunction, type 2 diabetes mellitus, slow growth, psychomotor delay, delayed speech development, hearing loss and cardiac malformations. Bbs diagnosis can be made with the presence of at least four cardinal features, or combination of three cardinal plus two secondary features 2. Bbs is mostly inherited as autosomal recessive trait, but there have been few reports that indicate oligogenic inheritance for BBS 3 4 5, However, this mode of inheritance has been under discussion 6 7 8 9. Bbs is a rare disorder with differences in prevalence of disease in different populations. For example, among total live births, in North America and Europe BBS affects 1 out of 140 000 - 160 000 10 11, but BBS is more common in Newfoundland 12 as well as in Kuwaiti bedouins 13 and Faroe Islands 14. These differences can be due to various factors, including consanguinity, which is social norm in countries such as Kuwait, Iran, Saudi Arabia and Pakistan. At genomic level, about 10% of the total genome has been estimated to be homozygous in such families 15. These homozygous regions generally contain causative genetic mutation in recessive disorders such as BBS. Genetic defect is usually inherited from a single ancestor and is passed to the father and mother of the affected child WHO ultimately carry identical disease - causing mutations in both alleles of gene 16 17 18. In Pakistan, more than 60% of total marriages are consanguineous, and of these, about 80% are among first cousins 16, which explains high frequency of homozygous mutations in families affected with recessive disorders. The prevalence of BBS in Pakistan is not yet know. To date, there have been only nine reports of 18 Pakistani families with mutations in eight genes already know to be involved in BBS: ARL6 19 20, BBS1 21, BBS2, BBS5 22, BBS9 23, BBS10 19 24 25, BBS12 22 26 and TTC8 27. Therefore, comprehensive studies are needed to further explore the genetic spectrum of BBS in the Pakistani population. In this study, four families with classical BBS and one family with BBS - like phenotype from Pakistan were genetically analyze. In total, four homozygous mutations were identify, including mutations in ARL6, BBS5, BBS9 and CEP164. Identify mutations in ARL6 and BBS5 is novel.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Challenges for Pakistan

Jianjun Chen, Qiwei Wang, Patricia E. Cabrera, Zilin Zhong, Wenmin Sun, Xiaodong Jiao, Yabin Chen, Gowthaman Govindarajan, Muhammad Asif Naeem, Shaheen N. Khan, Muhammad Hassaan Ali, Muhammad Zaman Assir, Fawad Ur Rahman, Zaheeruddin. Qazi, Sheikh Riazuddin, Javed Akram, S. Amer Riazuddin, J. Fielding Hejtmancik; Molecular Genetic Analysis of Pakistani Families With Autosomal Recessive Congenital Cataracts by Homozygosity Screening. Invest. Ophthalmol. Vis. Sci. 2017; 58: 2207 - 2217. Doi: https: / doi. Org / 10. 1167 / iovs. 17 - 21469. Purpose: To identify the genetic origins of Autosomal Recessive Congenital Cataracts in the Pakistani population. Methods: based on the hypothesis that most arCC patients in consanguineous families in the Punjab areas of Pakistan should be homozygous for causative mutations, affected individuals were screened for homozygosity of nearby highly informative microsatellite markers and then screened for pathogenic mutations by DNA sequencing. A total of 83 unmapped consanguineous families were screened for mutations in 33 known candidate genes. Results: Patients in 32 arCC families were homozygous for markers near at least 1 of 33 known CC genes. Sequencing includes genes that reveal homozygous cosegregating sequence changes in 10 families, 2 of which had the same variation. These include five missense, one nonsense, two frame shift, and one splice site mutations, eight of which were novel, in EPHA2, FOXE3, FYCO1, TDRD7, MIP, GALK1, and CRYBA4. Conclusions: above results confirm the usefulness of Homozygosity mapping for identifying Genetic defects underlying Autosomal Recessive disorders in consanguineous Families. In our ongoing study of arCC in Pakistan, including 83 arCC families that underwent Homozygosity mapping, 3 maps using genome - wide linkage Analysis in unpublished data, and 30 previously reported families, mutations were detected in approximately 37. 1% of all families study, suggesting that additional genes might be responsible in remaining families. The most commonly mutated gene was FYCO1, followed by CRYBB3, GALK1, and EPHA2. This provides the first comprehensive description of the genetic architecture of arCC in the Pakistani population.

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* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Genes and human diseases

Thalassemia is a family of hereditary genetic conditions that limit the amount of hemoglobin an individual can naturally produce. This condition inhibits oxygen flow throughout the body. There is a 25 percent chance that children who inherit the Thalassemia gene from both parents will be born with Thalassemia. People who are especially likely to be carriers of the faulty gene that is responsible for Thalassemia include those of Southeast Asian, Indian, Chinese, Middle Eastern, Mediterranean, and Northern African descent. With any form of Thalassemia usually comes severe anemia, which may require specialized care such as regular blood transfusions and chelation therapy.

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* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

How to prevent genetic diseases/disorders?

Genetic disorders are leading, causes and treatment of most of which is still unknown. Researchers and medical professionals are continuously doing research to find out causes and treatment methods for such diseases. These diseases are caused by mutations in the DNA of humans which are irreversible by traditional medical procedures and medicines. Which is also the reason such diseases are difficult to cure and patients having such diseases end up losing their lives. We can prevent or decrease the trend of such diseases by decreasing family marriage trend, genetic testing before marriages and precautionary measures which can help in the reduction of increasing trend of genetic diseases.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

National institute of genetic diseases

Findings suggest common speech problem,sss in some cases, may actually be inherited metabolic disorder. Stuttering may be the result of a glitch in the day - to - day process by which cellular components in key regions of the brain are broken down and recycle, say study in the Feb. 10 Online issue of New England Journal of Medicine. The study, led by researchers at the National Institute on Deafness and Other Communication Disorders, part of the National Institutes of Health, has identified three genes as source of stuttering in volunteers in Pakistan, United States, and England. Mutations in two genes have already been implicated in Other Rare metabolic Disorders also involved in cell recycling, while mutations in third, closely relate, gene have now been shown to be associated for the first time with disorder in humans. For hundreds of years, cause of stuttering has remained a mystery for researchers and health care professionals alike, not to mention people who stutter and their families, says James F. Battey, Jr., Md, ph. D, director of NIDCD. This is the first study to pinpoint specific gene mutations as potential cause of stuttering, disorder that affects 3 million Americans, and by doing so, might lead to dramatic expansion in our options for treatment. Stuttering is a speech disorder in which a person repeats or prolongs sounds, syllables, or words, disrupting the normal flow of speech. It can severely hinder communication and people's quality of life. Most children who stutter will outgrow stuttering, although many do not; roughly 1 percent of adults stutter worldwide. Current therapies for adults who stutter have focused on such strategies as reducing anxiety, regulating breathing and rate of speech, and using electronic devices to help improve fluency. Stuttering tends to run in families, and researchers have long suspected genetic component. Previous studies of stuttering in groups of families from Pakistan have been done by Dennis Drayna, ph. D, geneticist with NIDCD, which indicates place on chromosome 12 that was likely to harbor gene variant that cause this disorder. In latest research, Dr. Drayna and his team refined the location of this place on chromosome 12 and focused their efforts on new site. They sequence genes surrounding new marker and identified mutations in gene know as GNPTAB in affected family members. The GNPTAB gene is carried by all higher animals, and helps encode enzyme that assist in breaking down and recycling cellular components, process that takes place inside cell structure called the lysosome. They then analyzed genes of 123 Pakistani individuals who stutter, 46 from original families and 77 who are unrelated, as well as 96 unrelated Pakistanis who dont stutter, and who serve as controls. Individuals from the United States and England also took part in the study, 270 who stuttered and 276 who did

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

1. Down syndrome

Congenital heart disease is prevalent in 40% of patients with DS, and 0. 3% on non - DS. 7 8 Studies from Pakistan show that VSD and AVSD are two most prevalent CHD in DS patients in the country, with a prevalence of 60. 4% and 29. 1%, respectively. 9 10 However, our study shows that CAVSD has the greatest prevalence in DS patients, followed by VSD: 67% and 22%, respectively. Surgical correction of CHD in these patients usually involves greater risk of postoperative complications and mortality. 11 study in the United States on mortality associated with CHD from 1979 to 1997 shows increased life - expectancy of AVSD and VSD, suggesting improvements in management including surgical technique and peri - operative care. 5 Data from Pakistan also suggests that repair of partial atrioventricular canal has good outcomes with minimal mortality and that earlier repair reduces post - operative morbidity further. 12 Early repair of Congenital Heart Diseases also has the benefit of less expense, which is important in low resource setting like Pakistan. 13 Most DS patients in our study underwent repair at less than one year of age, which is consistent with other studies on AVSD repairs in DS patients. 14 presence of DS in patients significantly increases risk of severe morbidities that has a significant impact on recovery period, as well as on life expectancy even after successful CHD correction. 15 Our study shows trends of increased morbidity in the DS group,. However, it does not reach statistical significance, possibly due to small sample size. The mortality rate in DS patients was significantly higher than in non - DS patients, even after adjustment of confounders. Within this mortality group, 61. 5% were diagnosed with CAVSD. Cavsd is known to have poorer outcomes, longer median ventilation time, and intensive care unit and hospital stay, compared to other AVSD subtypes. 3 However, we do not find any reported deaths in non - DS patients with CAVSD. Interestingly, Western literature reports no significant difference or lower risk of mortality after AVSD correction in DS patients, which contrasts our findings. 6 16 This raises questions of possible differences in outcomes due to genetic, racial, environmental, and social factors which have not yet been explored in this region. This also highlights the need for developing indigenous guidelines for management of these pathologies. As currently, practices from other countries are being followed in Pakistan. Local guidelines were developed in India after the National Consensus Meeting on Management of Congenital Heart Diseases, 2018, which suggest that patients in the region are often underweight, malnourish, and have comorbidities such as recurrent infections and anemia. Several patients present late with advanced levels of pulmonary hypertension, ventricular dysfunction, hypoxia, and polycythemia. Therefore, outcome after surgery in such patients has a greater possibility of being undesirable, justifying the need for revised guidelines and practices with risk adjusted approach. 17 DS and non - DS patients have no significant differences in preoperative hemodynamics,. However, post - operative right heart pressures and pulmonary vascular resistance remain significantly high in DS patients compared to non - DS patients.

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* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

2. Huntingtons disease

Huntingtons disease is a rare genetic disorder caused by a mutation in a gene for protein called huntingtin. Mutation causes progressive destruction of brain cells, primarily in the region called basal ganglia. As a result, patients have difficulties controlling their movements, their emotions and behavior, and have trouble thinking. Disease worsens over time, with patients eventually losing the ability to walk, speak, or care for themselves and, thus, they becoming completely dependent on others. Huntington's disease is inherited in autosomal dominant pattern and thus anyone who inherits faulty gene eventually gets disease. A parent with a faulty gene has a 50% chance of passing the disease to his or her children. Huntingtons disease affects both men and women equally. Onset and progression of disease vary from one person to another. The most common form of disease occurs in middle - aged people and progresses slowly over the course of 15 to 20 years, with gradual loss of mental abilities and control of body movements. It can also occur in children, with symptoms usually beginning in teen years. In 2000, there were 30 000 cases of Huntington's disease in the US, according to Stanford University's Huntington's Outreach Project for Education, suggesting a prevalence rate of 100 cases per million people. Huntington's disease is a complex neuropsychiatric disease that produces three main types of symptoms: difficulty controlling movement, difficulty with emotions and behavior, and difficulty thinking. The most common movement problem is Chorea, which are large, jerky, dance - like movements. Other problems can include slowed movements, sustained twisting movements, small twitch - like movements in limbs, and difficulties speaking and swallowing. Problems with thinking can include difficulty paying attention, problems with mental planning and flexibility, inability to successfully perform mental tasks, and memory loss. These problems can appear before the first signs of motor impairment emerge. There can be emotional and behavioral changes that are particularly challenging for patients and family members as well. These can include anxiety, depression, lack of motivation, impulsivity, emotional outbursts, and mood swings. In first year after diagnosis, there is a higher incidence of depression and suicidal thoughts. As many as 40% of people with the condition may experience depressive symptoms. Speaking with a doctor is important if you or your loved one has this condition. Depressive or suicidal thoughts should be monitored closely. People with Huntington disease become increasingly impaired over the course of illness. In later stages of disease, patients lose the ability to walk or speak. They frequently lose significant amount of weight and can have difficulty sleeping. They usually become completely dependent on others for activities of daily living, such as dressing, grooming, and feeding. Ultimately, most common causes of death associated with this disease are pneumonia, aspiration of food or impaired swallowing, heart disease, and infections. Diagnosis requires complete neurological examination, including motor, sensory, neuropsychological, and psychiatric assessments. If results of this examination suggest that the patient has a disease, brain imaging, such as MRI, may be order.


Huntington's DiseaseLike Syndromes

Repeat expansions in C9orf72 have been associated with autosomal dominant frontotemporal dementia and / or amyotrophic lateral sclerosis. However, recognize clinical phenotypes are expanding. Among others, recently it has been suggested that C9orf72 expansions may be the most common genetic cause of HD phenocopies. 40 in a large genetic screening study, 10 of 514 HDL patients were found to carry C9orf72 mutations. 40 mean age at onset was 43 years. Early psychiatric and behavioral problems were common and were first symptom in six out of 10. Cognitive symptoms present as executive dysfunction. 40 Movement disorders were prominent: Three patients exhibited Chorea; four exhibited dystonia; four exhibited myoclonus; and three had tremor. Notably, six out of 10 patients had parkinsonian features and four patients had pyramidal features. 40 One may critizise that the presence of upper motor neuron signs is not typical for classic HD and should have been an exclusion criterion for genetic study. However, authors 40 elaborate that their cohort screen was composed of patients seen by experienced neurologists in whom diagnosis of HD was considered and thus reflect clinical reality. They stress 40 clinical diversity seen in HD, and that definition of HD phenocopy syndromes therefore needs to encompass not only classical HD triad but also syndromes having major degree of overlap with HD. We conclude that the presence of prominent pyramidal features may be a red flag to consider C9orf72 Repeat expansions in HDL patient. Mutation of C9orf72 is repeat expansion of six letter string of nucleotides GGGGCC. There is wide global distribution; however, it is mainly found in European populations but occurs exceptionally rarely in East Asian populations. 41 Repeat lengths up to 30 are considered normal. More than 30 repeatsgenerally 250 to 1 600 repeatsare detected in symptomatic patients. Protein plays a role as guanine nucleotide exchange factor for small guanosine triphosphatases regulating endosomal trafficking. Additional RNAmediated toxicity through accumulation of toxic RNA foci and RNAbinding proteins with secondary dysregulation of RNA splicing and trafficking has also been hypothesize.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Sources

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

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