In addition to FANCC, we have now undertaken HLA genotyping in more than two dozen cycles in combination with PGD for thalassemia, FANCA, hyperimmunoglobulin M syndrome (HIGM), X-linked adrenoleukodystrophy (X-ALD) and Wiscott-Aldrich syndrome (WAS), and X-linked hypohidrotic ectodermal displasia with immune deficiency (HED-ID) , confirming the usefulness of preimplantation HLA matching as part of PGD, which potentially provides an HLA-matched progeny for treatment of an affected sibling.
Among these conditions, the most prevalent ones are thalassemias, which are the most common autosomal recessive diseases in the Mediterranean region, Middle East, and Southeast Asia, with heterozygous frequency of thalassemia mutations reaching 14% in Greece and Cyprus. The prevalence of the other conditions is much lower, 1 in 17,000 for X-ALD, 1 in 100,000 for FA, and even rarer for WA, HIGM and HED-ID.
FANCA, similar to FANCC, is an autosomal recessive disorder causing an inherited bone marrow failure with increased predisposition to leukemia. As mentioned, bone marrow transplantation is the only treatment for FA, as it restores hematopoiesis in FANCA patients. However, because any modification of the conditioning is too toxic for these patients, as in FANCC, leading to a high rate of transplant-related mortality, the HLA-identical cord blood transplantation from a sibling is particularly valuable, to avoid late complications due to severe GVH, as mentioned above.
Beta-thalassemia is an autosomal recessive disease affecting the production of (3 -globin chains resulting in a severe anaemia, which makes the patients transfusion-dependent starting from six months after birth, so bone marrow transplantation is the only option for radical treatment. At present, 371 different mutations have been described in the (-globin gene, located in chromosome 11 (11p15.5), causing congenital anaemia of variable severity . Prenatal diagnosis has been applied widely for more than two decades resulting in considerable reduction of new cases of thalassemia in many populations . Considerable progress also has been achieved in treatment of the disease by bone marrow transplantation , the application of which is still limited to the availability of HLA-matched stem cells, making PGD an attractive option for couples with thalassemic children. PGD for thalassemia has already been provided for a few years , so HLA typing is presently offered in the same framework, allowing couples not only to avoid the birth ofanother child with thalassemia, but also to produce an unaffected child who may be an HLA match to the thalassemic sibling, and a potential stem cell donor.
X-ALD affects the nervous system and the adrenal cortex, with three main phenotypes. One of them manifests between ages 4 and 8 as attention deficit disorder, followed by progressive impairment of cognition and behaviour, vision, hearing, and motor function, leading to total disability within two years. Another pheno-type, called adrenomyeloneuropathy, manifests in the late 20s as progressive paraparesis, sphincter disturbances, and hearing loss, while the third presents with primary adrenocortical insufficiency by age 7-8. Regardless of the presence of symptoms, 99% of patients have an elevated concentration of very-long-chain fatty acids (VLCFA). The disease is caused by mutations of the ABCD1 gene, with more than 200 different mutations reported at the present time, which may be detected by PCR and direct sequencing, except for large deletions identified by Southern blot analysis. Carrier screening and prenatal diagnosis are available and the same method may be applied for PGD with simultaneous HLA typing.
HIGM is a rare immunodeficiency characterised by normal or elevated serum IgM levels, with absence of IgG, IgA, and IgE, which results in an increased susceptibility to infections, manifested in the first few years of life, and a high frequency of autoimmune haematological disorders, accompanied by gingivitis, ulcerative stomatitis, fever, and weight loss. HIGM is caused by
Was this article helpful?
Attention Deficit Disorder or ADD is a very complicated, and time and again misinterpreted, disorder. Its beginning is physiological, but it can have a multitude of consequences that come alongside with it. That apart, what is the differentiation between ADHD and ADD ADHD is the abbreviated form of Attention Deficit Hyperactive Disorder, its major indications being noticeable hyperactivity and impulsivity.