Scheckenbach Kathrin, Balz Vera, Wagenmann Martin, Hoffmann Thomas K
Department of Otorhinolaryngology, Heinrich-Heine-University, Düsseldorf, Germany.
BMC Med Genet. 2008 Dec 22;9:114. doi: 10.1186/1471-2350-9-114.
A combined aplasia, hypoplasia or atresia of lacrimal points and salivary glands is rarely diagnosed. Those patients suffer from epiphora, xerostomia and severe dental caries. This phenotype represents the autosomal-dominant aplasia of lacrimal and salivary glands syndrome (ALSG). Recently, aberrations of the Fibroblast Growth Factor 10 (FGF10) gene have been identified to be causative for this disorder.
We performed a sequence analysis of the FGF10 gene of a patient with ALSG-syndrome and his also affected brother as well as 193 controls. The FGF10 transcript was analyzed using RNA extracted from primary fibroblasts of the patient's mucosa.
We detected a novel heterozygous sequence variation in intron 2 (c.430-1, G > A) causing the ALSG syndrome. The alteration derogates the regular splice acceptor site and leads to the use of a new splice acceptor site 127 bp upstream of exon 3. The aberration was detected in the genomic DNA derived from two affected brothers, but not in 193 control individuals. Furthermore, no diseased member of the family displayed additional abnormalities that are indicative for the clinically overlapping lacrimo-auriculo-dento-digital syndrome (LADD).
This family-based approach revealed an intronic variation of the FGF10 gene causing ALSG-syndrome. Our results expand the mutational and clinical spectrum of the ALSG syndrome.
泪点和唾液腺联合发育不全、发育不良或闭锁的情况很少被诊断出来。这些患者患有流泪、口干和严重龋齿。这种表型代表常染色体显性遗传的泪腺和唾液腺发育不全综合征（ALSG）。最近，已确定成纤维细胞生长因子10（FGF10）基因异常是导致该疾病的原因。
我们对一名患有ALSG综合征的患者及其同样患病的兄弟以及193名对照者的FGF10基因进行了序列分析。使用从患者黏膜的原代成纤维细胞中提取的RNA对FGF10转录本进行了分析。
我们在第2内含子中检测到一个新的杂合序列变异（c.430-1，G>A），导致了ALSG综合征。该改变损害了正常的剪接受体位点，并导致在第3外显子上游127 bp处使用一个新的剪接受体位点。在来自两名患病兄弟的基因组DNA中检测到了这种异常，但在193名对照个体中未检测到。此外，该家族中没有患病成员表现出其他异常，这些异常提示临床上与之重叠的泪-耳-牙-指综合征（LADD）。
这种基于家族的研究方法揭示了FGF10基因的内含子变异导致ALSG综合征。我们的结果扩展了ALSG综合征的突变和临床谱。
