HLA haplotypes, polysomnography, and pedigrees in a case series of patients with narcolepsy.
HLA haplotypes, polysomnography, and pedigrees in a case series of patients with narcolepsy.
复制标题
发作性睡病患者病例系列的 HLA 单倍型、多导睡眠图和家系。
作者：
Hayduk,R;Flodman,P;Spence,MA;Erman,MK;Mitler,MM
一项正在进行的发作性睡病遗传学研究通过一系列发作性睡病先证者的病例，使用诊断标准来确定家族，诊断标准包括：1）过度嗜睡的临床病史，2）多次睡眠潜伏期试验（MPEG4）的平均睡眠潜伏期小于7.9分钟，3）快速眼动（REM）睡眠相关的catabolism症状，4）排除睡眠呼吸暂停综合征的夜间多导睡眠图，以及5）在MREM睡眠上的两个或更多个过渡。所有先证者和一级亲属接受临床和实验室评估以及人类白细胞抗原（HLA）分型。32名先证者的人口统计学特征如下：17名男性和15名女性;平均年龄为42.1岁（范围13-70岁）。多导睡眠图数据证实了32名先证者的白天嗜睡和REM睡眠趋势增加。夜间多导睡眠图结果如下：睡眠潜伏期，3.2分钟;总睡眠时间，442分钟。测试结果如下：睡眠潜伏期，3.1分钟; REM潜伏期，6.9分钟; REM周期数，3.2。HLA分型显示21名发作性睡病先证者存在HLA单倍型DRB 1 *15和DQB 1 *0602，其中2名非洲裔美国人具有DQB 1 *0602但不具有DRB 1 *15等位基因。在32例先证者的57名亲属中，女性1/31例，男性7/26例（P < 0.02），提示男性亲属中发作性睡病的诊断率较高。21例DRB 1 *15和DQB 1*0602单倍型阳性的先证者与10例这些等位基因阴性的先证者在夜间睡眠参数、MMPH结果或临床表现方面没有差异。三个家庭的多个人患有嗜睡症。两个家庭有一个以上的受影响的个人谁没有高危HLA单倍型。在这些家族中的一个中，疾病独立于任何HLA单倍型分离。在第三个家系中，存在与HLA DRB 1 *15和DQB 1*0602的共分离。一个家庭包含一对DNA证实的单卵双胞胎发作性睡病谁是不一致的catabolism和有HLA DR 14（DW 9）/DQB 1 *0503和DR 4（DW 4）/DQB 1 *0302单倍型。
An ongoing study of the genetics of narcolepsy ascertains families through a case series of narcoleptic probands using diagnostic criteria consisting of 1) clinical history of excessive somnolence, 2) a mean sleep latency on the multiple sleep latency test (MSLT) of less than 7.9 minutes, 3) the rapid eye movement (REM) sleep-related symptom of cataplexy, 4) nocturnal polysomnography ruling out sleep apnea syndrome, and 5) two or more transitions to REM sleep on the MSLT. All probands and first-degree relatives received clinical and laboratory evaluations as well as human leukocyte antigen (HLA) typing. Demographic characteristics of the 32 probands are as follows: 17 males and 15 females; mean age was 42.1 years (range 13–70 years). The polysomnographic data confirmed daytime sleepiness and increased tendency for REM sleep for the 32 probands. Nocturnal polysomnographic results are as follows: sleep latency, 3.2 minutes; total sleep time, 442 minutes. MSLT results are as follows: sleep latency, 3.1 minutes; REM latency, 6.9 minutes; number of REM periods, 3.2. HLA typing revealed the presence of the HLA haplotypes, DRB1*15 and DQB1*0602, in 21 narcoleptic probands, with two African-Americans having the DQB1*0602 but not the DRB1*15 allele. Among the 57 relatives of the 32 probands, 1/31 females and 7/26 males were found to be affected with narcolepsy (p < 0.02), which suggests a higher diagnostic rate in male relatives. The 21 probands who were positive for the DRB1*15 and DQB 1*0602 haplotypes did not differ from the 10 probands who were negative for these alleles in terms of their nocturnal sleep parameters, MSLT findings, or clinical presentation. Three families with multiple individuals affected with narcolepsy are presented. Two families have more than one affected individual who does not have the high-risk HLA haplotype. In one of these families, the disease is segregating independently of any HLA haplotype. In the third family, there is cosegregation with HLA DRB1*15 and DQB 1*0602. One family contains a pair of DNA-confirmed, monozygotic twins with narcolepsy who are discordant for cataplexy and have the HLA DR14(Dw9)/DQB1*0503 and DR4(Dw4)/DQB1 *0302 haplotypes.