Rev. Bras. Hematol. Hemoter. vol.25 número3

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191

Imagen s em Hematologi a Rev. bras. hematol. hemoter. 2003;25(3):191-192

IMAGENS EM HEMATOLOGIA/ IMAGES IN HEMATOLOGY

Car men S. P. Li ma

1

Gustavo J. Louren ço

1

Davi E. A. Rodri gu ez

2

Mari stela Zocca

1

Car men S. Bertuzzo

2

1

Haematology an d Haemotherapy Cen tre. 2

Departmen t of Medi cal Gen eti cs, State Un i versi ty of Campi n as, Campi n as, São Paulo, Brazi l.

Cytogenetic and Molecular Diagnosis of Fanconi Anemia

Diagnóstico citogenético e molecular da anemia de Fanconi

hyper-pigmentation, kidney and urinary tract

mal-formations, and high risk of developing a malignant

disease, particularly acute myelogenous leukaemia.

1

Somatic cell fusion studies have shown that FA is

genetically heterogeneous, resulting from mutations in

at least eight complementary gene groups (FANC A, B,

C, D1, D2, E, F, and G).

1

Lymphocytes culture shows an increased sensitivity

to the clastogenic agents diepoxybutane (DEB) or

mytomycin (MMC). These agents induce DNA damage,

mutations, chromosomal rearrangements and cell death

in FA patients.

2

_{The DEB test is considered as the gold}

Fanconi anaemia (FA) is an autosomal recessive

disorder associated with a very high frequency of bone

marrow failure, developmental abnormalities, such as

aplasia of the thumb and radius, growth retardation,

Fig. 1 – Chromosome spreads showi n g typi cal chromosome breaks (arrows) i n the Fan con i an aemi a pati en t an alysed by the di epoxybutan e test

Fi g. 2 – Pol ym er ase chai n r eacti on an d r estr i cti on en don uclease digestion for detection of IVS4+4A?T mutation of t h e FANCC gen e. Et h i d i u m br om i d e-st a i n ed 8 % pol ya cr yl a m i d e gel sh ow i n g f r a gm en t s of 1 0 8 bp correspon di n g to the absen ce of the mutati on an d fragmen ts of 131 bp correspon di n g to the presen ce of the mu tati on . Lan e 1 shows the DNA si ze markers Ladder 100 bp. Lan e 2 shows the r esu lt fr om an i n di vi du al wi th homozygou s mutation (Fan con i an aemia) an d lan es 3, 4 an d 5 show the results from heterozygous i n di vi duals of the same fami ly

Cor r espondence to: Carmen Si lvi a Passos Li ma, MD, PhD. Hemocen tr o – Un i camp – Ci dade Un i versi tári a “ Zeferi n o Vaz” . Cai xa Postal 6198, Cep: 13083-970 – Campi n as-SP – Brazi l

Phon e: + 55 19 3788-8729 – Fax: + 55 19 3788-8600 – E-mai l: carmen l@u n i camp.br

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Rev. bras. hematol. hemoter. 2003;25(3):191-192 Imagen s em Hematologia

standard for diagnosis of disease (reference). However,

its effectiveness has been questioned considering that

a negative test was found in some cases diagnosed by

molecular analysis.

3

Herein, we present one patient with aplastic

anaemia, who was diagnosed as FA by conventional

cytogenetic

2

_{and molecular}

4

_{analyses (Figures 1 and}

2). It is important to comment that both analyses

permitted proper management of the haematologic

disease and genetic counselling for the family.

Bibliogr aphic Refer ences

1. Owen J. Fanconi Anemia: Standards for Clinical Care. Fanconi Anemia Research Foundation Incorporation, Oregon, USA. p. 106, 1999.

2. Rosendorf J, Bernstein R, Macdougall L et al: Fanconi anemia: another disease of unusually high prevalence in the African population of South Africa. Am J Med Genet 1987;27:793-797.

3. Pearson T, Jansen S, Havenga C et al: Fanconi anemia: a statistical evaluation of cytogenetic results obtained from South African families. Cancer Genet Cytogenet 2001;126:52-55.

4. Gibson RA, Morgan NV, Goldstein LH et al: Novel mutations and polymorphisms in the Fanconi anemia group C gene. Human Mutat 1996;8:140-148.

Avaliação: Editor e um revisor externo

Conflito de interesse: não declarado

Recebi do: 11/07/2003

Acei to após modi fi cações: 15/08/2003