罕见的肾上腺脑白质营养不良家系的临床特点及基因突变

A clinical and genetic study of a rare adrenoleukodystrophy kindred

目的分析1个肾上腺脑白质营养不良(ALD)家系患者的临床特点,并检测致病基因ABCD1的突变类型。方法纳入一个4代受累、4例发病的汉族ALD家系。根据临床表现、头颅核磁共振显像及血清极长链脂肪酸浓度检测,明确ALD诊断。用聚合酶链反应及其产物直接测序法检测ABCD1突变。结果患者均为男性,表现为原发性肾上腺皮质功能减退和神经系统功能异常,大脑白质广泛脱髓鞘改变,血清极长链脂肪酸浓度明显升高。患者ABCD1基因第8外显子存在c.1850 G>T半合子突变,而女性携带者基因型为杂合子。结论原发性肾上腺皮质功能减退和神经系统功能异常是ALD的典型临床表现,ABCD1的c.1850 G>T错义突变是我国该疾病致病基因新的突变类型。

Objective To analyse the clinical features of a kindred with adrenoleukodystrophy （ALD） and to detect the mutation of ABCD1 gene. Methods A Chinese ALD kindred with four affected males from four-generations was studied. ALD was diagnosed according to clinical manifestations, cranial MRI image and serium level of very long chain fatty acid （VLCFA）. Mutation of ABCD1 was detected by direct DNA sequencing of polymerase chain reac- tion amplification product. Results Primary adrenocortical insufficiency and neurological dysfunction were the main manifestations of the patients. MRI image showed extensive cerebral white matter demyelination. Serum VLCFA level was significantly high. A novel missense substitution（ c. 4037 C 〉 T） in exon 8 of ABCD1 was identi- fied. All affected males were hemizygotes and female carriers were heterzygotes. Conclusions The typical manifes- tations of ALD are primary adrenocortical insufficiency and neurological dysfunction. A missense substitution （c. 4037 C 〉 T） in exon 8 of ABCD1 is a novel mutation firstly detected in this Chinese pedigree with ALD.