Havlovicová M, Propper L, Novotná D, Musová Z, Hrdlicka M, Sedlácek Z
Ustav biologie a lékarské genetiky, LF UK a FNM, Praha.
Cas Lek Cesk. 2002 Jun 21;141(12):381-7.
Many observations indicate that genetic factors play an important role in the aetiology of autism. Up to now, however, no genetic markers have been convincingly identified which influence the predisposition to this disorder. Complex genetic analysis of autistic patients and their families may therefore lead to the identification of features which could help to direct further search for the predisposing genes.
We have analysed a sample of 20 patients with autism spectrum disorders. The patients have been subjected to clinical genetic examination, cytogenetic analysis and DNA analysis of the FMR1 gene. In the sample studied we have observed more boys (15/20), various degree of mental retardation (18/20), high frequency of complications during pregnancy (10/20) and delivery (10/20), increased incidence of psychiatric disorders, behavioural abnormalities and suicides among the relatives, and increased head circumference and unusually formed ears in the probands. Three patients had different chromosomal aberrations or variants (t(21;22), inv(9) and inv(10)). One patient harboured expansion of the trinucleotide repeat sequence in the FMR1 gene on the full mutation level which is characteristic for the fragile X syndrome, and one patient is suspected to suffer from the Rett syndrome.
Our observations confirm and extend the results reported in the literature. Most interesting are mainly the macrocephaly which may be associated with the recently described increased neonatal levels of neural growth factors in autistic individuals, ear malformations which may indicate aberrations in the HOXA1 gene pathway, the occurrence of chromosomal inversions recurrent in autism, and peculiarities in the pedigrees of the patients.
许多观察结果表明，遗传因素在自闭症的病因中起着重要作用。然而，到目前为止，尚未令人信服地确定影响这种疾病易感性的遗传标记。因此，对自闭症患者及其家庭进行复杂的遗传分析可能会导致识别出有助于指导进一步寻找易感基因的特征。
我们分析了20例自闭症谱系障碍患者的样本。这些患者接受了临床遗传检查、细胞遗传学分析和FMR1基因的DNA分析。在研究的样本中，我们观察到男孩更多（15/20）、不同程度的智力迟钝（18/20）、孕期（10/20）和分娩期（10/20）并发症的高发生率、亲属中精神疾病、行为异常和自杀的发生率增加，以及先证者头围增大和耳朵形态异常。3例患者有不同的染色体畸变或变异（t(21;22)、inv(9)和inv(10)）。1例患者在FMR1基因上存在三核苷酸重复序列的全突变水平扩增，这是脆性X综合征的特征，1例患者疑似患有雷特综合征。
我们的观察结果证实并扩展了文献报道的结果。最有趣的主要是可能与最近描述的自闭症个体新生儿神经生长因子水平升高相关的巨头畸形、可能表明HOXA1基因途径异常的耳部畸形、自闭症中反复出现的染色体倒位的发生以及患者家系中的特殊性。
