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Genodermatoses: Genetic Counseling and Prenatal Diagnosis

Prenatal diagnosis (PND) has become technically possible in cases where there is at high risk of severe genetic disease, thanks to recent advances in molecular biology and diagnostic technology. In dermatology, PND of severe skin diseases can be performed at the request of the parents. However, genetic counseling should be thoroughly and carefully made from the ethical point of view, and patients and their families should be provided with accurate information on the diseases. It is important to remember that the final decision of confirmation of pregnancy should always be left to the client. This chapter compiles genodermatoses and their causative genes and proteins, and introduces the latest advances in PND, genetic counseling and gene therapy.

A. Genodermatoses Outline ● The

term “genodermatoses” tends to refer to monogenic diseases. ● In recent years, the causative genes and proteins have been identified for many genodermatoses. MEMO Updated information of the human genome and genetic diseases

What are genodermatoses? “Genodermatoses” usually refers to diseases caused by monogenic abnormality. This textbook addresses genetic diseases separately in terms of their clinical features: It describes ichthyosis in the chapter on keratinization, epidermolysis bullosa in that on blistering diseases, and oculocutaneous albinism in that on disorders of skin color. The human genome project, which was completed in 2003, mapped and sequenced the 3 billion nucleotides in the human genome to identify all human genes. It has been clarified that the human genome consists of 22,000 genes, which produce about 100,000 proteins. Accordingly, almost all of the genes and proteins that are responsible for monogenic diseases including genodermatoses are being clarified. The major genodermatoses and the causative genes and proteins that have been identified so far are shown in Table 29.1. Nevertheless, the pathogeneses of multifactorial genetic diseases, such as psoriasis vulgaris and atopic dermatitis, have not been fully resolved. These diseases are not usually referred to as genodermatoses. The genes that are associated with the onset of these diseases are called disease-related genes or predisposing factors; their importance to the disease is considerably different from that of monogenic causative genes for genodermatoses.

The pathological conditions of genodermatoses are being clarified every day, and what was once common knowledge is no longer enough in responding to patients and their families. Fortunately, improvements of information technology, including the Internet, have contributed to the spread of up-todate information on the human genome and genetic diseases. This information is now available for free to anyone. ① The National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/) The site provides updated information on the Human Genome Project. ② Online Mendelian Inheritance in Man (OMIM) (http://www.ncbi.nlm.nih.gov/entrez/ query.fcgi?db=OMIM/) Six thousand human Mendelian disorders and their characteristics are listed. The latest information and documents on diseases caused by genetic mutation, gene maps and images are available. The diseases are categorized and numbered as a matter of convenience. For example, autosomal dominant inherited diseases are designated by numbers from 100,000, autosomal recessively inherited diseases by numbers from 200,000, X-linked inherited diseases by numbers from 300,000, and mitochondrial inherited diseases by numbers from 500,000. Clinical conditions caused by genetic mutation are compiled separately in clinical synopsis.

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Genodermatoses: Genetic Counseling and Prenatal Diagnosis

Table 29.1 Main genodermatoses and their causative genes and proteins.    





     

    

          

  

      



   

   

     

  



  

 

  

   

  

     

    

 

    

     



 

    

   

 



       

  

    

   



   

   

 

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A. Genodermatoses

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Table 29.1 Main genodermatoses and their causative genes and proteins (cont.).      

  

 

 



   

   

 

 

  

 



     

   

  

  

 

 

  

 



  

 



     

   

 



      

  

   

 

    

  

              

 



    

  

      

 



 



   

  

 



             

     

    

      

         

 

        

   

   

      



           

 

    

  

    

 

  

 

    

        

 

      

 

      

   

          

    

     

 



               

   

 



     

              

                  

     

 

     

     

      

          

 



 



   

 



    

 



 



     

    

 



   

 

 

         

                   





  

   

   

    

      

       





     

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AD: autosomal dominant inheritance, AR: autosomal recessive inheritance, XR: X-linked recessive inheritance, SD: semidominant

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