Detection of de novo mutations and analysis of their origin in families with X linked hypohidrotic ectodermal dysplasia.
Detection of de novo mutations and analysis of their origin in families with X linked hypohidrotic ectodermal dysplasia.
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X 连锁少汗性外胚层发育不良家族中新生突变的检测及其起源分析。
DOI：
10.1136/jmg.31.4.287
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发表时间：
1994
影响因子：
4
通讯作者：
Thomas,NS
中科院分区：
文献类型：
--
作者：
Zonana,J;Jones,M;Clarke,A;Gault,J;Muller,B;Thomas,NS
通过物理和遗传作图方法，已将少汗性外胚层发育不良（EDA）定位于X染色体的q12-q13.1区域。虽然使用紧密连锁的侧翼标记进行连锁分析可以澄清许多女性的携带者状态，在可能的从头突变的情况下，突变的起源知识是准确的家庭遗传咨询的关键。已使用两种方法来确认EDA家族中的从头突变并追踪其起源。直接检测三个从头分子缺失，卵子发生过程中产生的，其他两个在精子发生过程中，实现了Southern分析，使用从EDA区域分离的cosmetic作为探针。七个从头突变在精子发生过程中产生的，和两个可能的从头突变在卵子发生过程中，被确定的共分离的疾病与多态性标记紧密连锁和侧翼的EDA位点的分析。对10个新突变起源的确认和分析极大地帮助了这些家庭的遗传咨询。在未鉴定突变类型的家族中，男性与女性的突变来源明显超过3.5：1，这与X连锁疾病的其他研究相似，并表明这些突变中的大多数可能涉及单碱基对取代。
Hypohidrotic ectodermal dysplasia (EDA) has been localised to the q12-q13.1 region of the X chromosome by both physical and genetic mapping methods. Although linkage analysis using closely linked flanking markers can clarify the carrier status for many females at risk for the disorder, knowledge of the origin of the mutation in instances of possible de novo mutation is critical for accurate genetic counselling of families. Two methods have been used to confirm de novo mutation in families with EDA and to trace their origin. Direct detection of three de novo molecular deletions, one arising during oogenesis and the other two during spermatogenesis, was achieved by Southern analyses using cosmids isolated from the EDA region as probes. Seven de novo mutations arising during spermatogenesis, and two possible de novo mutations during oogenesis, were identified by an analysis of the cosegregation of the disorder with polymorphic markers closely linked to and flanking the EDA locus. The confirmation and analysis of the origin of the 10 de novo mutations greatly assisted genetic counselling in these families. The apparent 3.5:1 excess of male to female origin of mutation in families studied with unidentified types of mutation is similar to other studies of X linked disorders, and suggests that the majority of these mutations may involve single base pair substitutions.
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影响因子：
9.8
作者：
R. Ketterling;E. Vielhaber;C. Bottema;D. Schaid;Melinda P. Cohen;Charles L. Sexauer;Steve S. Sommer
通讯作者：
R. Ketterling;E. Vielhaber;C. Bottema;D. Schaid;Melinda P. Cohen;Charles L. Sexauer;Steve S. Sommer
外胚层发育不良综合征中的出汗。
影响因子：
--
作者：
D. Berg;D. Weingold;K. G. Abson;E. Olsen
通讯作者：
E. Olsen
检测 X 连锁少汗性外胚层发育不良 (EDA) 患者 DXS732 基因座的分子缺失，并鉴定出独特的连接片段。
影响因子：
9.8
作者：
Zonana,J;Gault,J;Davies,KJ;Jones,M;Browne,D;Litt,M;Brockdorff,N;Rastan,S;Clarke,A;Thomas,NS
通讯作者：
Thomas,NS
影响因子：
4
作者：
CRAWFORD, PJM;ALDRED, MJ;CLARKE, A
通讯作者：
CLARKE, A
X 连锁少汗性外胚层发育不良 (EDA) 基因座的高分辨率图谱。
影响因子：
9.8
作者：
Zonana,J;Jones,M;Browne,D;Litt,M;Kramer,P;Becker,HW;Brockdorff,N;Rastan,S;Davies,KP;Clarke,A
通讯作者：
Clarke,A