Characterisation and genetic mapping of a new X linked deafness syndrome.
Characterisation and genetic mapping of a new X linked deafness syndrome.
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一种新的 X 连锁耳聋综合征的特征和遗传图谱。
DOI：
10.1136/jmg.37.11.836
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发表时间：
2000
影响因子：
4
通讯作者：
Petty,EM
中科院分区：
文献类型：
--
作者：
Martin,DM;Probst,FJ;Camper,SA;Petty,EM
背景遗传性听力损失被归类为综合征型，当耳聋与其他临床特征相关时，或非综合征型，当耳聋发生时，没有其他临床特征。许多类型的综合征性耳聋已被描述，其中一些已被映射到特定的染色体区域。方法我们描述了一个由明显的X连锁隐性遗传传递的进行性感音神经性耳聋、认知障碍、面部畸形和各种其他特征的家系。跨越X染色体的PCR产物的单倍型分析和候选基因的直接测序被用来开始表征该家族传递的特征的分子基础。通过回顾已发表的报告和个人讨论，与涉及耳聋、智力低下、面部畸形和其他临床特征的已知综合征进行比较。结果遗传图谱将该综合征的候选基因定位在XQ1-21上48 cM的区域内。包括COL4A5、DIAPH和POU3F4在内的候选基因被临床和分子分析排除。结论该家系的一系列临床表现(耳聋、认知障碍、面部畸形、可变的肾脏和泌尿生殖系统异常以及晚发型全血细胞减少)以及XQ1-21上的共同单倍型表明，这代表了一种新的综合征性耳聋。我们将我们的发现与其他几个已被定位到X染色体上的综合征型和非综合征型耳聋基因座进行了比较。
BACKGROUNDHereditary forms of hearing loss are classified as syndromic, when deafness is associated with other clinical features, or non-syndromic, when deafness occurs without other clinical features. Many types of syndromic deafness have been described, some of which have been mapped to specific chromosomal regions.METHODSHere we describe a family with progressive sensorineural hearing loss, cognitive impairment, facial dysmorphism, and variable other features, transmitted by apparent X linked recessive inheritance. Haplotype analysis of PCR products spanning the X chromosome and direct sequencing of candidate genes were used to begin characterising the molecular basis of features transmitted in this family. Comparison to known syndromes involving deafness, mental retardation, facial dysmorphism, and other clinical features was performed by review of published reports and personal discussions.RESULTSGenetic mapping places the candidate locus for this syndrome within a 48 cM region on Xq1-21. Candidate genes includingCOL4A5, DIAPH,andPOU3F4were excluded by clinical and molecular analyses.CONCLUSIONSThe constellation of clinical findings in this family (deafness, cognitive impairment, facial dysmorphism, variable renal and genitourinary abnormalities, and late onset pancytopenia), along with a shared haplotype on Xq1-21, suggests that this represents a new form of syndromic deafness. We discuss our findings in comparison to several other syndromic and non-syndromic deafness loci that have been mapped to the X chromosome.