Tuesday, 16 August 2011

Clinical Radiological Pathological Conference: August 2011. A female with sexual development problem

Clinical-Radiological-Pathological conference is the monthly acticity held by Department of Medciine, Faculty of Medicine, Chulalongkorn University.
There is presentation of a case and discussion by clinician (internal medicine staff), radiologist and a diagnostician (usually pathologist but can be any one aware of the final diagnosis such as microbiologist, geneticist, parasitologist or clinicians)
The CRPC case will be recorded and posted on our department website: http://forum.cumedicine.org/index.php?board=6.0

Before the date of CRPC, there is the active discussion board in another webboard: http://forum.cumedicine.org/index.php?topic=528.msg2181#new

This month, the CPC case is a 18-year-old woman who presented with primary amenorrhea, secondary sex characteristics underdevelopment, and a large lobulated heterogeneous enhancing mass with amorphous calcification in the pelvic cavity.

Who are interested in case discussion can follow the link and leave the comments.

Reference for the discussion: Books: Genetic Disorders of Human Sexual Development: Leonard Pinsky, Rober P Erickson and R Neil Schimke. http://ukcatalogue.oup.com/product/9780195109078.do
Orphanet: http://www.orpha.net/consor/cgi-bin/index.php
Gene reviews: http://www.ncbi.nlm.nih.gov/books/NBK1116/
OMIM: http://www.ncbi.nlm.nih.gov/omim

Sunday, 7 August 2011

Medical Genetics residency training in USA

Medical genetics residency training is relatively new medical specialty training in USA. As the growing body of genetic knowledge, the realization of application in practical medicine, this field has been developed but in a slow pace than previous expectation. Doctors who have been enrolled in the training will sit for the examination for board certification of clinical genetics. Only MD can be entered into this type of training. Currently, there are about 1000 american board certified medical geneticists in US and elsewhere in the world. This number is only about 1% of all doctors.

There are other three laboratory based subspecialty training: biochemical genetics, molecular genetics and cytogenetics which allow both MD and non MD doctorate graduate to enter this type of training. Another genetics sub specialty training are molecular genetics pathology and Neurogenetics that are run by American Board of Pathology and American board of neurology and psychiatry respectively. We will focus on training that are accredited by board of medical genetics.

Pathway of training

1.single specialty training with or without subspecialty training

2.combined specialty training (combined with internal medicine/ pediatrics or OB-GYN)

The first one is the most common pathway. There are about 50 programs owned for this type of training. These are the list of accredited programs from all states in USA.

or you can follow this link: http://www.acgme.org/ for accredited programs search.
The eligible for enter each programs are set different by institution but the eligibility for sit in the exam for amedican board of medical genetics are set and evaluated by American Board of Medical Genetics as followings:

Training Requirements for Certification

Foreign Medical Graduates Credentials Check

Individuals seeking ABMG certification must fulfill all of the requirements for certification, as detailed in this document. Individuals who hold doctoral degrees earned outside of the US, Canada, or Puerto Rico or who underwent medical training outside of the US, Canada, or Puerto Rico, may need to meet additional requirements.

Doctoral degree requirements for each genetics specialty are as follows:

Clinical Genetics………………………...MD or DO

Clinical Cytogenetics……………………MD, DO, or PhD*

Clinical Biochemical Genetics…………. MD, DO, or PhD*

Clinical Molecular Genetics……………..MD, DO, or PhD*

*PhD must be in genetics, human genetics or a related field, as determined by the ABMG.

The Clinical Genetics specialty training requirements include:

24 months of satisfactorily completed full-time training in an ACGME-accredited residency program in a specialty (other than clinical genetics) that is recognized by the ABMS, (e.g., pediatrics, obstetrics and gynecology, internal medicine, etc.) and an additional 24-months of satisfactorily completed full-time training in an ACGME-accredited clinical genetics residency training program;


48 months of satisfactorily completed full-time training in an ACGME-accredited 4-year clinical genetics residency. (Note: In this instance the 48 months of training satisfy both the graduate medical training requirement and the medical genetics residency training requirement);


60 months of satisfactorily completed full-time training in an ACGME-accredited combined residency such as pediatrics/medical genetics, internal medicine/medical genetics, or obstetrics and gynecology/medical genetics. Upon successful completion of all the requirements of the combined residency, a trainee is qualified to apply for certification by either the American Board of Pediatrics (ABP), the American Board of Internal Medicine (ABIM), or the American Board of Obstetrics and Gynecology (ABOG) (depending on the other discipline) and the ABMG. Applicants must satisfactorily complete the specific credentialing requirements of each board to be eligible to sit for the examination of that board. Certification in one specialty is not contingent upon certification in the other specialty.

The laboratory specialties (Clinical Biochemical, Clinical Cytogenetics and Clinical Molecular Genetics) training requirements include a minimum of 24 months of satisfactorily completed full-time training in an ABMG-accredited laboratory genetics training program.

For certification in each additional ABMG specialty (except Clinical Genetics): an additional 12 months of completed full-time training in an ABMG-accredited fellowship program in that specialty is required. For certification in Clinical Genetics as an additional ABMG specialty, the same requirements as those detailed above in IB apply.

Number of months of ABMG-approved medical genetics training to be completed by number of ABMG specialty certifications sought:

Number of ABMG

primary specialty certifications* Months of completed ABMG-approved medical genetics training

1 24 months

2 36 months

3 48 months

4 60 months

*Note: Certification in Clinical Genetics always requires 24 months of completed training in an ACGME-accredited clinical genetics residency.


Credentialing Requirements and Process

The credentialing process determines an applicant’s candidate status for the ABMG certifying examination. All documents required for the credentialing process must be submitted to the ABMG Administrative Office and postmarked by the deadline (see Deadlines, Section VI).

Full training options can be found at American Boards of Medical Genetics website

Thursday, 4 August 2011

genetics and skin colours: Human pigmentation: genetics and biology and cat coat colors

Skin colours are determined by genetics. Genetics of skin colours although quite complex. Racial skin colours are rather crude determination of human skin colours. This article will talk about skin colours in disease: albino and their underlying genetic mechanisms. The link of skin colours in human and albino might entertain the reader here.

There are large variations of cat coat colors which make cat breeders, cat lovers and scientists intrigue about the nature of these different shades, colors and patterns of their skin and fur for centuries. Until recently, that the comparative molecular genetics and newly developed techniques can uncover the genetic basis of these interesting characteristics of cats. These article series will talk about cat coat, color characters, and patterns and their genetic mechanisms and linking to human skin pigmentation understanding.

Skin and hairs or fur colors of mammalians including humans and cats are determined by many types of pigments. The most important one is called melanin. The cell produce melanin is called melanocytes. These cells are normally situated in the layer of skin cells or keratinocytes. Melanocytes will produce melanin by changing tyrosine, an amino acid, by the enzyme called tyrosinase through multiple steps.

There is constitutive production that is different among races and can be generally classified into three human races: Caucasian: white skin, Mongoloids: yellow skin and Negroids: dark skin. In cats, there is no such major groups. So we can see solid cats with color ranging from light brown, grey, to pure black. (Other characters and pattern will be discussed later) The production will be increased in some situations such as light, friction and injuries, or chemical agents and some disease states that can be generalized or localized such as freckles, melanoma, or malignant melanoma. Some genetic syndromes has increase incidence of these pigment disorders such as neurofibromatosis, McKune-Albright syndrome, Noonan syndrome and its spectrums.

In contrary, the rate of production can be reduced from various physical agents, chemical and disease conditions too. The disease with lowering production of melanin in human is called vitiligo that is usually localized but sometime can be generalized. A disease that has multiple small area of depigmentation causes only cosmetic problem. The disease as a fancie name: Hypomelanosis of Ito. The normal rate of production is primarily determined by racial difference in human and breed in cats and also the genetic mutation might switch off the production of melanin pigment at all which is so called albino. In the cat with complete no production of melanin pigments, the skin and fur are white, eyes will be in blue color. In human, all the hairs will be white and skin is also creamy white. Eyes are also blue like the cat eyes. This albino is called Oculocutaneous type 1a. Both cats and humans with this type of albino will have high incidence of skin cancers unravel the importance of melanin pigment for prevention of photodamage.

If the process is incomplete disruption, there will be some melanin produced leading to various level of dark color range from very light skin and hair to somewhat near normal pigment production. Clinical recognition of this mild form of albino is called Oculocutaneous type 1b. Normally, there will be no pigment production from birth like type 1 but lately produce some amount of melanin pigments that make light-brown or hazel color iris and dark eyelashes with some tanning of the skins. Oculocutaneous type I is autosomal dominant inherited. That means that the patients usually have one parent that also has the same condition. There is about 50% chance for transmission of the disease to the offspring and both male and female can be equally affected.

Recently, we found some families with typical type I albinism but with autosomal recessive like inherited pattern. There is no parent with the diseases but siblings. The parents are both carriers of the disease and normally, there will be some degree of consanguineous marriage. Genetic mutation underlying of this type of autosomal recessive albino is unknown.

There is some interesting feature of the pigment producing that leads to cat fanciers interest. It is called temperature sensitive albino. Some mutations in the tyrosinase genes make them sensitive to temperature change. It stops producing melanin when the temperature is high. So the terminal parts of their body that is colder will be darker than the body that is the characteristics of Siamese pointed cat breed, mink Tonkinese and Sepia Burmese breed. It is more interesting that we also found many families with show the features like this temperature sensitive albino cat breeds. Some areas that are less warn: facial and pubic hairs develop slightly pigmentation and arms and leg hairs which is cold will be normally pigmented.

Albino Chimpanzi and his normal friend http://mathiasbyabato.blogspot.com/2009/10/albino-in-tanzania.html

Temperature sensitive albino cat (Siamese cat - pointed breed)
Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC329910/pdf/jcinvest00487-0361.pdf A Tyrosinase Gene Missense Mutation in Temperature-sensitive Type I Oculocutaneous Albinism
The same document with more demonstrative picture can be found at http://factaboutthecat.blogspot.com/