الفهرس 
BASIC PRINCIPLES OF GENETICSOnly 14 pages are availabe for public view
 |  | from | 2 |  |  |
| | | from | 2 | | |
Abstract
G
enodermatoses are inherited disorders with prominent dermatologic manifestations. The Mendelian inheritance of human disease has been recognized over a century. The discovery of specific gene mutation leading to genodermatoses is more recent event. Since the completion of Human Genome Project in 2003 and the development of rapid, high-throughput sequencing technologies, the number of disorders linked to specific mutations has exploded.
Genodermatoses are a heterogeneous group of disorders with a wide range of underlying DNA alterations. These alterations range from single gene mutation to contiguous gene deletions or larger chromosomal abnormalities to complex and polygenic mechanisms. By definition, genodermatoses are potentially inheritable since the mutations are germline not somatic. Genodermatoses are typically inherited in classic Mendelian fashion autosmal dominant (AD), autosomal recessive (AR), X-linked dominant (XLD) and X-linked recessive (XLR). As with other genetic diseases more complex inheritance pattern like non-classical inherited disorders exist, including X-inactivation, imprinting, and mitochondrial inheritance, to name a few. With many of the genodermatoses, individuals have sporadic, or de novo, mutations (not inherited by parents, but in the individuals germline due to post-zygotic mutation which occurs during mitotic division of the cells of embryo) (Hosler and Murphy, 2014).
Prenatal diagnoses of inherited skin diseases were first introduced in the 1980s with a fetal skin biopsies. Fetal skin biopsies were undertaken under fetoscopy or ultrasound guidance using small forceps. The biopsied specimen could be examined with light and electron microscopy for morphological abnormalities. The subsequent development of monoclonal antibodies or biochemical techniques made it possible to evaluate abnormalities in the protein level of fetal skin samples. One of the inevitable disadvantages of fetal skin biopsies is that they can be performed only during the second trimester of pregnancy at around 18-20 weeks of gestation (Shimizu, 1999).
Applications of molecular biological techniques have allowed the identification of specific mutant genes responsible for a number of inherited skin diseases. Based on the same approach, various techniques used in a molecular biology/genetics laboratory with special focus on polymerase chain reaction (PCR), gene sequencing, genotyping, DNA micro arrays and Linkage analysis has become possible for a range of severe inherited skin diseases, including recessive dystrophic EB, Herlitz junctional EB, Dowling-Meara EB simplex, tyrosinase negative oculocutaneous albinism, bullous congenital ichthyosiform erythroderma, Sjogren-Larsson syndrome, lamellar ichthyosis. A chorionic villus sampling at 10 weeks’ gestation or amniocentesis at 13 weeks’ gestation during the first trimester can be carried out to obtain fetal DNA for prenatal testing. The diagnosis can be made in 24 to 48 hours through DNA analysis, and the results obtained before the pregnant mother feels the first fetal movement (Hiremagalore, et al., 2008).
Advances in technology of genetic diagnosis, DNA-based prenatal tests, to the first attempts at preimplantation genetic haplotyping in 2007 using some of the latest molecular techniques available. Laboratory protocols are becoming quicker and technically easier and, therefore, counseling of couples at risk of recurrence of a specific disease should include mention of the significant and clinically relevant advances that are occurring in this field. An attractive option is the potential of testing free fetal DNA/RNA in the maternal circulation. This can be conducted within the first few weeks of pregnancy following a simple blood test (Fassihi, 2008).
Genetic Counseling an educational process by which patients at risk, individuals are given information to understand the nature of the genetic disease, its transmission and the options open to them in management and family planning. Genetic counseling is an integral part of the management of patients and families with genetic disorders.
Essential Components of Genetic Counseling:
• History and pedigree construction and clinical examination
• Confirmatory diagnosis
o History findings
o Clinical examination findings
o Laboratory parameter results
o DNA studies results
o Radiology findings
• Calculation of recurrence risk, available options, management, prevention and counseling to promote informed choices and adaptation to risk or condition and follow-up.
Prevention of genetic skin disorders
• Primary prevention is to prevent birth of an affected child, by premarital screening to identify carrier status or preconceptional genetic counseling and preimplantation genetic diagnosis (PGD).
• Secondary prevention is to prevent clinical manifestations in affected cases. By prenatal diagnostic and neonatal screening.
• Tertiary prevention to provide of adequate care and rehabilitation in affected individuals.
The recent advances in gene therapy provide the possibility of long term treatment for the more severe genodermatoses. This includes advances in vector technology, targeted gene expression, gene replacement, gene correction and the control of immune responses. The use of gene therapy, protein replacement and cell-based therapies (Stem cells and fibroblasts) for these severe disorders provides an opportunity for improving the outcome for many patients (Long, et al., 2009).