Bikhazi P H, Roeder E, Attaie A, Lalwani A K
Laboratory of Molecular Otology, Epstein Laboratories, San Francisco, California, USA.
Am J Otol. 1999 Sep;20(5):639-43.
Advancements in molecular genetics has direct impact on the evaluation and management of patients and family members with familial paragangliomas (FP).
Familial paragangliomas. in contrast to sporadic cases, are commonly multiple, bilateral, and present at an earlier age. Familial tumors are inherited in an autosomal dominant pattern with genomic imprinting of the paternal allele. Mapping studies have identified regions on chromosome 11q as harboring the genetic defect responsible for paraganglioma formation.
A multigenerational family with five affected females with head and neck paragangliomas underwent clinical and genetic evaluation. Genetic mapping was performed with microsatellite markers froin chromosome 11q13 and q23. Nonaffected individuals were screened for carrying the affected haplotype. In addition, by using DNA obtained from an amniotic fluid sample. in utero screening of a fetus was performed.
The most common complaints were hearing loss and neck masses that usually manifested by age 25. Genetic mapping identified loci 11q13 and q23 as sites likely responsible for tumorogenesis. Three unaffected family members, including a fetus, were identified as carriers of the affected haplotype. The genetic findings were used to design a screening protocol for family members at risk for developing glomus tumors.
Genetic screening of unaffected family members can identify individuals harboring the mutated allele. Identification of family members at risk for developing FP by molecular genetic techniques may lead to early detection of head and neck paragangliomas and may directly impact morbidity from glomus tumors and their treatment.
分子遗传学的进展对患有家族性副神经节瘤（FP）的患者及其家庭成员的评估和管理有直接影响。
与散发性病例相比，家族性副神经节瘤通常为多发、双侧性，且发病年龄较早。家族性肿瘤以常染色体显性模式遗传，父本等位基因存在基因组印记。定位研究已确定11号染色体q区域含有导致副神经节瘤形成的遗传缺陷。
对一个有五名患有头颈部副神经节瘤的受影响女性的多代家族进行了临床和基因评估。使用来自11号染色体q13和q23的微卫星标记进行基因定位。对未受影响的个体进行筛查，以确定是否携带受影响的单倍型。此外，通过使用从羊水样本中获得的DNA，对一名胎儿进行了宫内筛查。
最常见的症状是听力丧失和颈部肿块，通常在25岁时出现。基因定位确定11q13和q23位点可能是肿瘤发生的部位。三名未受影响的家庭成员，包括一名胎儿，被确定为受影响单倍型的携带者。这些基因研究结果被用于设计针对有发生球瘤风险的家庭成员的筛查方案。
对未受影响的家庭成员进行基因筛查可以识别携带突变等位基因的个体。通过分子遗传学技术识别有发生FP风险的家庭成员可能会导致头颈部副神经节瘤的早期发现，并可能直接影响球瘤的发病率及其治疗。
