Iida S, Tanaka Y, Fujii H, Hayashi S, Kimura M, Nagareda T, Moriwaki K
Internal Medicine, Minami Wakayama National Hospital, Tanabe, Wakayama 646, Japan.
Int J Mol Med. 1998 Jun;1(6):925-9. doi: 10.3892/ijmm.1.6.925.
Lhermitte-Duclos disease is a rare disorder of the cerebellum which exhibits a focally indolent growth of the cerebellar cortex. The disease is sometimes associated with multiple hamartoma syndrome, or Cowden disease, an autosomal, dominantly inherited cancer syndrome. Germline mutations of the PTEN/MMAC1 gene, a gene recently discovered to be a tumor suppressor, have been documented in four families with Cowden disease. A family member in one of these families have had Lhermitte-Duclos disease, indicating that mutations of the gene are responsible for the development of Lhermitte-Duclos disease. However, the occurrence of Lhermitte-Duclos disease is mostly sporadic. It is unknown whether the PTEN/MMAC1 gene is involved in these cases. We performed a genetic analysis on a patient with Lhermitte-Duclos disease, as well as analyses on his family members, and found a germline mutation of the PTEN/MMAC1 gene. An insertion of A at nucleotide 83 in codon 28 was apparent in both the patient and members of his family. This mutation caused a frame shift that generated a premature stop codon in codon 43. The mutation was heterozygous, although only the mutated allele was expressed in the cerebellar tumor of the patient. A monoallelic expression of the mutated PTEN/MMAC1 gene may have been responsible for the development of a cerebellar tumor in the patient.
Lhermitte-Duclos病是一种罕见的小脑疾病，表现为小脑皮质局部生长缓慢。该疾病有时与多发性错构瘤综合征或考登病相关，考登病是一种常染色体显性遗传的癌症综合征。PTEN/MMAC1基因是最近发现的一种肿瘤抑制基因，在四个考登病家族中记录到该基因的种系突变。其中一个家族的一名成员患有Lhermitte-Duclos病，这表明该基因的突变是Lhermitte-Duclos病发病的原因。然而，Lhermitte-Duclos病的发生大多是散发性的。尚不清楚PTEN/MMAC1基因是否与这些病例有关。我们对一名Lhermitte-Duclos病患者及其家庭成员进行了基因分析，发现了PTEN/MMAC1基因的种系突变。在患者及其家庭成员中均明显存在第28密码子第83位核苷酸处的A插入。这种突变导致了移码，在第43密码子处产生了一个提前终止密码子。该突变是杂合的，尽管只有突变等位基因在患者的小脑肿瘤中表达。突变的PTEN/MMAC1基因的单等位基因表达可能是导致患者小脑肿瘤发生的原因。
