Carrier frequency of the common mutation IVS8-IG>C in DHCR7 and estimate of the expected incidence of Smith-Lemli-Opitz syndrome
Carrier frequency of the common mutation IVS8-IG>C in DHCR7 and estimate of the expected incidence of Smith-Lemli-Opitz syndrome
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DOI：
10.1006/mgme.2000.3103
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发表时间：
2001-01-01
影响因子：
3.8
通讯作者：
Steiner, RD
中科院分区：
文献类型：
--
作者：
Battaile, KP;Battaile, BC;Steiner, RD
Smith-Lemli-Opitz综合征（SLOS）是一种严重程度不等的多发性先天性异常/智力低下综合征，根据病例频率调查，以前的发病率估计为1 / 20,000-60,000，SLOS基因缺陷的发现使得利用分子方法识别携带者计算携带者频率和估计疾病发病率成为可能。使用先前描述的PCR-RFLP分析，我们从随机新生儿筛查血点卡中筛选1503份匿名血液样本，以确定常见sls突变IVS8-1G>C的存在，以确定携带者频率。在1503份样品中鉴定出16种载体。由于已知所有sls基因突变中IVS8-1G>C突变的频率，因此可以计算出所有突变的总体载子频率，根据该结果计算出所有突变的载子频率为1 / 30，预测sls发病率为1 / 1590 ~ 1 / 13500。因此，目前的发病率估计可能大大低估了sls的真实发病率。计算和观察到的发病率之间的差异可能是由于未确诊的轻度病例、误诊的重症病例、诊断前死亡或胎儿丢失。需要更全面的发病率研究来确定SLOS是否像本研究中确定的非常高（1 / 30）的载体频率所预测的那样普遍。(C) 2001学术出版社。
Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital anomaly/mental retardation syndrome of variable severity with an incidence previously estimated at 1 in 20,000-60,000 based on case frequency surveys, Identification of the gene defect in SLOS has made it possible to calculate the carrier frequency and estimate disease incidence using molecular methods to identify carriers. Using a previously described PCR-RFLP assay we screened 1503 anonymous blood samples from random newborn screening blood spot cards for the presence of the common SLOS mutation IVS8-1G>C in order to determine the carrier frequency. Sixteen carriers were identified in the 1503 samples. Since the frequency of the IVS8-1G>C mutation among all SLOS gene mutations is known, the overall carrier frequency for all mutations can be calculated, The calculated carrier frequency for all mutations based on this result is 1 in 30, predicting an SLOS incidence of 1 in 1590 to 1 in 13,500. The current incidence estimate may, therefore, significantly underestimate the true incidence of SLOS. This discrepancy between calculated and observed incidence could be due to undiagnosed mild cases, misdiagnosed severe cases, death prior to diagnosis, or fetal loss, More comprehensive incidence studies are needed to determine if SLOS is as common as predicted by the very high (1 in 30) carrier frequency determined in this study. (C) 2001 Academic Press.