Characterization of chromosome rearrangements in patients with multiple congenital malformation and/or mental retardation (MCM/MR) / Caracterização de rearranjos cromossômicos em pacientes com malformações congênitas múltiplas e/ou retardamento mental (MCA/MR)

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Two apparently "de novo" balanced translocations and one duplication of the short arm of chromosome 20 were studied. Our aim was to determine the breakpoints by chromosomal analysis through fluorescentin situ hybridization (FISH) and identify candidate genes and how they were involved with the clinical phenotypes of the patients. Patient 1 carried a duplication of the short arm of chromosome 20 (p11.22p13), inherited from the mother that showed normal and dup(20) lymphocytes. The duplication was determined by FISH using BAC and PAC clones, and nine clones were duplicated except one (20p11.21). The patient shared many of the common characteristics of trisomy 20p including delay in motor development, hypertelorism, poor coordination, round face with prominent cheeks, vertebral and dental abnormalities and cranial asymmetry with high and large forehead. She also had learning difficulties, behavioral disorders and pubertal growth spurt at 12 years. As our patient is an example of pure trisomy 20p, the features are of particular importance to delineate the syndrome. Three genes were mapped on the segment that contain the duplication (20p11.2-13), one of these genes is the SSTR4 (Somatostatin receptor 4). The somatostatin is widely distributed throughout the body and is important regulator of endocrine and nervous system function. It is an inhibitor of growth hormone secretion. The second gene is the BMP2 that produce bone morphogenetic proteins and it has a direct function with the nervous system. The third gene is the GHRH that produce proteins connected with the growth hormone. These genes might have been over expressed and thus contributing to the patients clinical features. Patient 2, carried a 46,XY,t(5;14)(q14.1;q31.3)de novo translocation. On chromosome 14 the breakpoint was mapped to a segment contained in BAC RP11-315O17 (14q31.3). On the chromosome 5 the breakpoint was mapped to a segment contained in BAC RP11-30D15 (5q14.1). Although the breakpoint, on the chromosome 14, has been mapped in 14q31.3, our patient shared many of the common characteristics of terminal 14q32 deletion: mental retardation, dolicocephaly, prominent ears, hypertelorism, strabismus, upturned palpebral fissures, highly arched palate, simian crease, severe myopia, coloboma and palpebral ptosis. As mental retardation and ocular abnormalities were the main patients clinical features, we are suggesting that: 1) a region of segment 14q31.3 was deleted. 2) A gene inside this segment (14q31.3) could be responsible for ocular development and 3) a disrupted gene could interfere on the expression of other genes. On chromosome 5 eleven genes were localized and four of them are expressed in nervous system (AP3B1; SCAMP1; BHMT2 e CMYA5). One of these genes might have been disrupted and is contributing to the patients clinical features. Patient 3 was the carrier of a 46,XY,t(1;15)(p13.2;q25.2)de novo translocation. The breakpoint on chromosome 15 was mapped to the segment contained in clone RP11-152F13 (15q25.2). The breakpoint on chromosome 1 was mapped to the segment contained in clone RP5-1037B23 (1p13.2). The genes mapped at the breakpoint regions of chromosome 1 and chromosome 15 are expressed in nervous system and muscles. Our patient shows few clinical features: speech delay, stutter and learning difficulties, probably because one or more of these genes, mapped at the breakpoint region, could be disrupted.

ASSUNTO(S)

chromosome breakpoints rearranjos cromossômicos estruturais candidate genes pontos de quebra cromossômicos structural chromosome rearrangements genes candidatos

ACESSO AO ARTIGO

Documentos Relacionados