Gonçalves Fernanda T, Fridman Cintia, Pinto Emília M, Guevara-Aguirre Jaime, Shevah Orit, Rosembloom Arlan L, Hwa Vivian, Cassorla Fernando, Rosenfeld Ron G, Lins Theresa S S, Damiani Durval, Arnhold Ivo J P, Laron Zvi, Jorge Alexander A L
Laboratório de Imunohematologia e Hematologia Forense (LIM40), Departamento de Medicina Legal, Ética Médica e Medicina Social e do Trabalho, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Am J Med Genet A. 2014 May;164A(5):1204-8. doi: 10.1002/ajmg.a.36444. Epub 2014 Mar 24.
Laron syndrome (LS) is a genetic disorder caused by mutations in the growth hormone receptor (GHR) gene. The most frequent GHR mutation is E180splice (rs121909360), which was initially found in an inbred population of Spanish descent in Ecuador and subsequently in Israel, Brazil, Chile, and the United States. The aim of the present study is to determine if the E180splice mutation arose from a common origin. We studied 22 patients with LS from Ecuador, Israel (of Moroccan origin), Brazil, Chile, and the United States (of Mexican origin) who were homozygous for the E180splice mutation and compared them to control individuals for markers surrounding the GHR, intragenic polymorphisms, and Y-chromosome STR. An identical haplotype was found in all but one of the subjects carrying the E180splice mutation: D5S665: 150/150; D5S2082: 192/192; D5S2087: 246/246; rs6179 G/G; and rs6180 C/C. One patient differed from the others only at D5S2082 (168/192). This haplotype is rare (~1%) in control individuals and confirmed that the E180splice-associated haplotype was not derived from independent origins but represented recombination from a common ancestor. The analysis of paternal lineage markers showed that 50% belong to haplogroup R1b (found in Portugal and Spain) and 40% to haplogroups J and E (typical in the Middle East and in Eastern European Jews). The germline E180Splice mutation appears to have originated from a single common ancestor. The presence of Y-chromosome markers associated with Sephardic populations in persons harboring the E180splice mutation provides genetic evidence in support of the historical tracking of the exodus of this specific population.
拉龙综合征（LS）是一种由生长激素受体（GHR）基因突变引起的遗传性疾病。最常见的GHR突变是E180剪接突变（rs121909360），最初在厄瓜多尔有西班牙血统的近亲群体中发现，随后在以色列、巴西、智利和美国也有发现。本研究的目的是确定E180剪接突变是否起源于共同的祖先。我们研究了来自厄瓜多尔、以色列（摩洛哥裔）、巴西、智利和美国（墨西哥裔）的22例E180剪接突变纯合子的LS患者，并将他们与对照个体进行比较，分析GHR周围的标记、基因内多态性和Y染色体短串联重复序列（STR）。在所有携带E180剪接突变的受试者中，除一人外，均发现了相同的单倍型：D5S665：150/150；D5S2082：192/192；D5S2087：246/246；rs6179 G/G；以及rs6180 C/C。一名患者仅在D5S2082位点（168/192）与其他患者不同。这种单倍型在对照个体中很罕见（约1%），证实了与E180剪接相关的单倍型并非源自独立起源，而是代表了来自共同祖先的重组。对父系谱系标记的分析表明，50%属于单倍群R1b（在葡萄牙和西班牙发现），40%属于单倍群J和E（在中东和东欧犹太人中典型）。种系E180剪接突变似乎起源于一个共同的祖先。在携带E180剪接突变的个体中存在与西班牙裔人群相关的Y染色体标记，为这一特定人群的历史迁徙追踪提供了遗传学证据。
