Verhoef S, Schrander-Stumpel C T, Vuzevski V D, Tempelaars A, Jansen L A, Malfeyt G A, Ceelen T L, Lindhout D, Halley D J, van den Ouweland A M
Department of Clinical Genetics EE2422, Erasmus University, Rotterdam and Academic Hospital, Rotterdam Dijkzigt, The Netherlands.
J Med Genet. 1998 Oct;35(10):841-5. doi: 10.1136/jmg.35.10.841.
A large Dutch family had been known for many years to be affected with skin tumours labelled as adenoma sebaceum, which were inherited in an autosomal dominant fashion. Since this skin sign is considered pathognomonic for tuberous sclerosis complex, the condition in the family was labelled accordingly, in the absence of further clinical features of tuberous sclerosis complex-like mental retardation or epilepsy. The skin changes started at early puberty with small eruptions around the nose and progressed to larger tumours, with considerable variation in severity. Some affected members had required plastic surgical reconstruction following excision. Linkage analysis in this family was performed for the two chromosomal regions involved in tuberous sclerosis complex on chromosomes 9q34 and 16p13, but no positive linkage was found. On critical re-evaluation of the clinical and pathological data and renewed assessment, the working diagnosis was changed to autosomal dominant cylindromatosis. The recently published candidate region for cylindromatosis on chromosome 16q12-13 was subsequently proven to be positively linked with a lod score of 3.02 with marker D16S308. Review of pathological specimens confirmed the diagnosis of cylindromatosis. DNA analysis of tumour tissue showed loss of heterozygosity for the cylindromatosis CYLD1 locus. These results confirm the candidate locus for cylindromatosis on chromosome 16q12-13.
一个荷兰大家庭多年来一直受一种被称为皮脂腺瘤的皮肤肿瘤影响，这种肿瘤以常染色体显性方式遗传。由于这种皮肤体征被认为是结节性硬化症的特征性表现，所以在没有结节性硬化症其他临床特征（如智力发育迟缓或癫痫）的情况下，该家族的病症被相应地标记为结节性硬化症。皮肤变化始于青春期早期，鼻子周围出现小疹，之后发展为更大的肿瘤，严重程度差异很大。一些患者在切除肿瘤后需要进行整形手术重建。对这个家族进行了9号染色体长臂3区4带和16号染色体短臂13区涉及结节性硬化症的两个染色体区域的连锁分析，但未发现阳性连锁。在对临床和病理数据进行严格重新评估并再次评估后，初步诊断改为常染色体显性遗传性圆柱瘤病。最近公布的16号染色体长臂12区至13区圆柱瘤病候选区域随后被证明与标记D16S308呈阳性连锁，连锁值为3.02。病理标本复查证实了圆柱瘤病的诊断。肿瘤组织的DNA分析显示圆柱瘤病CYLD1位点杂合性缺失。这些结果证实了16号染色体长臂12区至13区为圆柱瘤病的候选位点。
