Johns Hopkins University, Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, California 92093-0935, USA.
Am J Med Genet A. 2012 Aug;158A(8):1902-8. doi: 10.1002/ajmg.a.35467. Epub 2012 Jul 11.
Individuals with cystinosis exhibit specific cognitive deficits in visual spatial function. The purpose of the current study was to examine if obligate heterozygotes of the CTNS mutation have the same pattern of cognitive functioning seen in homozygotes, namely aberrant visual-spatial functioning against a background of relatively intact visual-perceptual functioning and overall cognitive ability. Study participants were 254 adults (100 heterozygotes and 154 controls), ages 17 years 10 months through 74 years 9 months. Tests of intelligence, visual perceptual, and visual spatial functioning were administered. Our results showed that cystinosis heterozygotes demonstrated intelligence within the normal range, and performed similarly to controls on tests of visual-perceptual ability. In contrast, the heterozygotes performed significantly more poorly on each of the visual-spatial tests when compared to controls. Obligate heterozygotes for the CTNS mutation display a similar pattern of visual processing decrements as do individuals with cystinosis. Namely, carriers demonstrate relative weaknesses in visual-spatial processing, while maintaining normal visual perceptual ability and intelligence in the normal range. The visual spatial decrements in heterozygotes were not as marked as those found in individuals with cystinosis, suggesting a gene dosing effect. This study provides an impetus for other studies of gene-behavior relationships in recessive disorders, and may stimulate further interest in the role of aberrant genes on "individual differences" in behavior.
胱氨酸病患者表现出特定的视觉空间功能认知缺陷。本研究的目的是检验 CTNS 基因突变的强制性杂合子是否具有与纯合子相同的认知功能模式，即异常的视觉空间功能，而视觉感知功能和整体认知能力相对完整。研究参与者为 254 名成年人（100 名杂合子和 154 名对照），年龄为 17 岁 10 个月至 74 岁 9 个月。进行了智力、视觉感知和视觉空间功能测试。我们的结果表明，胱氨酸病杂合子的智力在正常范围内，并且在视觉感知能力测试中与对照组表现相似。相比之下，与对照组相比，杂合子在每项视觉空间测试中的表现明显较差。CTNS 基因突变的强制性杂合子表现出与胱氨酸病患者相似的视觉处理缺陷模式。即，携带者在视觉空间处理方面表现出相对较弱的能力，同时保持正常的视觉感知能力和智力在正常范围内。杂合子的视觉空间缺陷不如胱氨酸病患者明显，表明存在基因剂量效应。这项研究为隐性疾病中基因-行为关系的其他研究提供了动力，并可能进一步激发对异常基因在行为“个体差异”中的作用的兴趣。
