A case of familial central precocious puberty caused by a novel mutation in the makorin RING finger protein 3 gene.
A case of familial central precocious puberty caused by a novel mutation in the makorin RING finger protein 3 gene.
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DOI：
10.1186/s12902-015-0056-8
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发表时间：
2015-10-23
影响因子：
2.7
通讯作者：
Perrone L
中科院分区：
文献类型：
--
作者：
Grandone A;Cantelmi G;Cirillo G;Marzuillo P;Luongo C;Miraglia del Giudice E;Perrone L
中枢性性早熟（CPP）通常是家族性的，但其遗传原因在很大程度上是未知的。最近，在5个家族性早熟家系中发现了位于15号染色体Prader-Willi综合征（PWS）相关区域（15 q11-q13）的Makorin RING finger protein 3（MKRN 3）基因突变。MKRN 3是一种母体印记基因，只有当MKRN 3突变位于从父亲遗传的等位基因上时，表型才会表达。该基因的功能尚不完全清楚，其缺陷引起的表型尚未完全阐明。我们报告了一个新的MKRN 3突变（Pro 160 Cysfs *14）引起家族性CPP。指示病例是一名7岁女孩，显示坦纳3期和阴毛1期。TW 2法骨龄10.3岁。她的激素数据证实了中枢性性早熟的诊断。家族病史显示父系堂兄弟性早熟。祖母9岁零6个月初潮，36岁时过早绝经。遗传分析揭示了一个新的突变（c477_485del; Pro 160 Cysfs *14）在母系印迹MKRN 3。另一名受影响的女性家庭成员在5岁时开始青春期。性早熟通过药物治疗得到良好控制。我们扩大了与CPP相关的MKRN 3突变的数量，并强调了准确的家族病史的重要性，以揭示该基因的特殊遗传模式。
Central precocious puberty (CPP) is often familial but its genetic cause is largely unknown. Very recently, the makorin RING finger protein 3 (MKRN3) gene, located on chromosome 15 in the Prader-Willi syndrome (PWS)-associated region (15q11-q13), has been found mutated in 5 families with familial precocious puberty. The MKRN3 is a maternal imprinted gene and the phenotype is expressed only when the MKRN3 mutations are localized on the allele inherited from the father. The function of this gene is not completely known and the phenotype caused by its defect is not yet fully elucidated. We report a new MKRN3 mutation (Pro160Cysfs*14) causing familial CPP. The index case is a 7 years old girl showing Tanner stage 3 and pubic hair stage 1. Her bone age evaluated by TW2 method was 10.3 years. Her hormonal data confirmed the diagnosis of central precocious puberty. Familial medical history revealed precocious puberty in a cousin on paternal side. Paternal grandmother had menarche at the age of 9 years and 6 months and premature menopause when she was 36 years old. Genetic analysis revealed a new mutation (c477_485del; Pro160Cysfs*14) in the maternally imprinted MKRN3. Puberty onset was at 5 years in the other affected female family member. Precocious puberty was well controlled by pharmacological therapy. We expand the number of the MKRN3 mutations associated with CPP and highlight the importance of an accurate family medical history to disclose the peculiar pattern of inheritance of this gene.