Durand Adélaïde, Bashamboo Anu, McElreavey Ken, Brauner Raja
Fondation Ophtalmologique Adolphe de Rothschild and Université Paris Descartes, Paris, France.
Human Developmental Genetics, Institut Pasteur, Paris, France.
BMC Endocr Disord. 2016 Sep 13;16(1):50. doi: 10.1186/s12902-016-0130-x.
The mechanism that initiates the onset of puberty is largely unknown but the age of onset is mainly under genetic control and influenced by environmental factors including nutrition. The coexistence in the same family of central precocious puberty and advanced puberty, both representing early puberty, suggests that they may represent a clinical spectrum of the same trait due to early activation of the GnRH pulse generator. We therefore evaluated the mode of inheritance of early puberty in a large series of familial cases.
A retrospective, single center study was carried out on 154 probands (116 girls and 38 boys), from 139 families seen for idiopathic central precocious puberty (onset before 8 years in girls and 9-10 years in boys, n = 93) and/or advanced puberty (onset between 8 and 10 years in girls and 10 and 11 years in boys, n = 61) seen over a period of 8 years.
Of the 139 families, 111 (80.4 %) had at least one affected 1st degree relatives, 17 (12 %) had only 2nd, 5 (3.6 %) only 3rd and 3 (2.2 %) had both 2nd and 3rd degree affected individuals. In the two remaining families, the unaffected mother had affected girls from two unaffected fathers. In the majority of families the inheritance of the phenotype was consistent with autosomal dominant mode of transmission with incomplete penetrance. An exclusively maternal mode of transmission could be observed or inferred in 83 families, paternal in only 2 families (p < 0.0001) and both maternal and paternal modes in 15 families. In the 139 families, 374 cases of early puberty were identified of whom 315 (84.2 %) were affected females and 59 (15.8 %) affected males (p < 0.0001). Twenty one percent of families had exclusively precocious puberty, 25 % had exclusively advanced puberty and 54 % had combinations of both.
The data confirm the high incidence of affected girls with familial early puberty. The mode of inheritance of the phenotype is predominantly maternal. More than half of the families included both precocious and advanced puberty suggesting similar genetic factors.
启动青春期开始的机制很大程度上尚不清楚，但青春期开始的年龄主要受遗传控制，并受包括营养在内的环境因素影响。中枢性性早熟和青春发育提前在同一家族中共存，二者均代表青春期提前，这表明它们可能是由于GnRH脉冲发生器的早期激活而代表同一性状的临床谱。因此，我们在一大系列家族性病例中评估了青春期提前的遗传模式。
对来自139个家庭的154名先证者（116名女孩和38名男孩）进行了一项回顾性单中心研究，这些家庭因特发性中枢性性早熟（女孩8岁前、男孩9 - 10岁前发病，n = 93）和/或青春发育提前（女孩8至10岁、男孩10至11岁发病，n = 61）前来就诊，研究为期8年。
在139个家庭中，111个（80.4%）至少有一名受影响的一级亲属，17个（12%）仅有二级亲属受影响，5个（3.6%）仅有三级亲属受影响，3个（2.2%）二级和三级亲属均有受影响个体。在其余两个家庭中，未受影响的母亲有来自两个未受影响父亲的受影响女儿。在大多数家庭中，该表型的遗传符合常染色体显性遗传模式且具有不完全外显率。在83个家庭中可观察到或推断出仅为母系遗传模式，仅2个家庭为父系遗传模式（p < 0.0001），15个家庭为母系和父系遗传模式。在139个家庭中，共识别出374例青春期提前病例，其中315例（84.2%）为受影响女性，59例（15.8%）为受影响男性（p < 0.0001）。21%的家庭仅有性早熟，25%的家庭仅有青春发育提前，54%的家庭二者皆有。
数据证实家族性青春期提前中受影响女孩的发生率较高。该表型的遗传模式主要为母系遗传。超过一半的家庭同时存在性早熟和青春发育提前，提示遗传因素相似。
