FISH characterisation of an identical (16)(p11.2p12.2) tandem duplication in two unrelated patients with autistic behaviour
FISH characterisation of an identical (16)(p11.2p12.2) tandem duplication in two unrelated patients with autistic behaviour
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DOI：
10.1136/jmg.2003.016311
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发表时间：
2004-07-01
影响因子：
4
通讯作者：
Larizza, L
中科院分区：
文献类型：
--
作者：
Finelli, P;Natacci, F;Larizza, L
16p部分三体是一种罕见的新生儿染色体异常：在迄今报道的不到30例携带者中，大多数新生儿的父母都有16号染色体p臂的平衡易位。据报道，在7名患者中发现了纯16p部分三体，其中3人（均表现出自闭症特征的行为问题）携带了16p的串联重复（p11）。2-p12)区域4 6；仅有1例患者出现轻微畸形。4连锁研究表明，16p染色体是自闭症易感基因的主要位置，7而自闭症特征与注意缺陷或多动障碍之间的关联被报道定位于16p13带。此外，导致结节性硬化症（一种通常与自闭症特征相关的综合征）的基因之一TSC2也位于相同的细胞遗传带。我们报道了一名携带a基因的患者的临床表型和精细的分子细胞遗传学特征（16）。2 p12。2)重复。通过将FISH分析扩展到先前描述的具有明显相似染色体重排的患者6，我们发现低拷贝重复映射到16p11。2和16p12。2个重复终点，提示非等位基因同源重组为发病机制。这一发现与观察到的非随机发生的染色体重排和在整个16号染色体中发现的高频率的片段重复一致。10-12我们还从基因型-表型相关研究中推断，与自闭症易感性相关的基因位于重复区域内。病例报告：患者1为25岁男性，无血缘关系父母的长子。在他出生时，他的母亲30岁，他的父亲29岁。他足月出生时体重为2.550公斤（第3百分位）。
Partial trisomy 16p is a rare chromosomal anomaly in newborns: of the fewer than 30 carrier patients so far reported, most were born to parents with a balanced translocation involving the p arm of chromosome 16. 1 Pure partial trisomy 16p has been reported in seven patients, 2–6 three of whom (all showing behavioural problems with autistic traits) carried a tandem duplication of the (16)(p11. 2–p12) region4 6; minor dysmorphisms were reported in only one patient. 4 Linkage studies indicated chromosome 16p as a major location for autism susceptibility genes, 7 while association was reported between autistic traits and attention deficit or hyperactivity disorders mapping to the 16p13 band. 8 In addition TSC2, one of the genes responsible for tuberous sclerosis, a syndrome often associated with autistic traits, maps to the same cytogenetic band. 9 We report the clinical phenotype and refined molecular cytogenetic characterisation of a patient carrying a (16)(p11. 2p12. 2) duplication. By extending the FISH analysis to a previously described patient with an apparently similar chromosomal rearrangement, 6 we found that low copy repeats map to the 16p11. 2 and 16p12. 2 duplication endpoints, suggesting non-allelic homologous recombination as the pathogenetic mechanism. This finding is consistent with the non-random occurrence of the observed chromosomal rearrangement and the high frequency of segmental duplications identified throughout chromosome 16. 10–12 We also inferred from genotype-phenotype correlation studies that genes involved in autism susceptibility are located within the duplicated region.CASE REPORT Patient 1 is a 25 year old man, the first son of unrelated parents. At the time of his birth, his mother was aged 30 and his father 29 years. He was born at term with a weight of 2.550 kg (3rd centile).