Stratakis C A, Lin J P, Rennert O M
Unit on Genetics and Endocrinology, Section on Pediatric Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862, US.
Am J Med Genet. 1998 Sep 23;79(3):209-14.
It has been suggested that branchio-oculo-facial (BOF) syndrome, deafness with ear pits, and associated conditions [MIM nos. 125100, 120502], and branchio-oto-renal (BOR) [MIM no. 113650] or Melnick-Fraser syndrome represent phenotypic variants of the BOR syndrome, which is inherited in an autosomal dominant (AD) manner and has variable clinical expression. Recently, the BOR gene was mapped to chromosome region 8q13.3 and its sequence was identified as the human homolog of the Drosophila eyes absent (EYA1) gene. We studied an extended family with AD inheritance of branchial arch anomalies (BAA), hearing loss, and ear pits, whose phenotype differed from that of patients with BOR in that none of the affected members had renal abnormalities or lacrimal duct stenosis. Fifteen affected members were studied; ear pits were present in all of them, whereas hearing loss and other BAA were present in 40 and 20%, respectively. Blood was collected from 31 patients; DNA was extracted by standard methods and amplified using primers from microsatellite sequences flanking the BOR locus on chromosome 8q13.3 (D8S1807, D8S530, and D8S543). Linkage analysis was performed under two models of AD inheritance with different penetrance: 100% and 80%. In both cases, the logarithm of odds (LOD) scores produced were significantly less than -2; exclusion of the 8q13.3 locus was also confirmed by multipoint LOD score analysis. We conclude that, in one large family with AD inheritance of BAA, hearing loss and ear pits, the BOR locus was excluded. This represents the first documentation of heterogeneity in branchio-oto anomalies, syndromes with phenotypes similar to BOR syndrome.
有人提出，鳃-眼-面（BOF）综合征、伴有耳凹的耳聋及相关病症[《医学遗传学国际疾病分类》编号：125100、120502]，以及鳃-耳-肾（BOR）[《医学遗传学国际疾病分类》编号：113650]或梅尔尼克-弗雷泽综合征代表了BOR综合征的表型变异，该综合征以常染色体显性（AD）方式遗传且具有可变的临床表型。最近，BOR基因被定位到染色体区域8q13.3，其序列被确定为果蝇无眼（EYA1）基因的人类同源物。我们研究了一个具有AD遗传的鳃弓异常（BAA）、听力损失和耳凹的大家庭，其表型与BOR患者不同，因为所有受影响成员均无肾脏异常或泪管狭窄。对15名受影响成员进行了研究；所有人都有耳凹，而听力损失和其他BAA分别出现在40%和20%的成员中。从31名患者采集了血液；通过标准方法提取DNA，并使用位于染色体8q13.3上BOR基因座侧翼的微卫星序列引物进行扩增（D8S1807、D8S530和D8S54）。在两种不同外显率的AD遗传模型下进行连锁分析：100%和80%。在这两种情况下，产生的优势对数（LOD）分数均显著小于-2；多点LOD分数分析也证实了8q13.3基因座的排除。我们得出结论，在一个具有BAA、听力损失和耳凹AD遗传的大家庭中，排除了BOR基因座。这是鳃-耳异常（表型与BOR综合征相似的综合征）中异质性的首次记录。
