The E180splice mutation in the GHR gene causing Laron syndrome: Witness of a Sephardic Jewish exodus from the Iberian Peninsula to the New World?

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 Unit...

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Published in:	American journal of medical genetics. Part A Vol. 164A; no. 5; pp. 1204 - 1208
Main Authors:	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.
Format:	Journal Article
Language:	English
Published:	United States Blackwell Publishing Ltd 01-05-2014 Wiley Subscription Services, Inc
Subjects:	Brazil Chromosomes, Human, Y DNA, Mitochondrial Ecuador Female growth hormone insensitivity growth hormone receptor growth hormone receptor deficiency Haplotypes Homozygote Humans Israel Jews - genetics Laron syndrome Laron Syndrome - diagnosis Laron Syndrome - genetics lineage markers Male Microsatellite Repeats mitochondrial haplogroups Mutation Receptors, Somatotropin - genetics RNA Splice Sites Y-chromosome haplogroups Brazil Ecuador Israel growth hormone insensitivity Laron syndrome growth hormone receptor mitochondrial haplogroups Y-chromosome haplogroups growth hormone receptor deficiency lineage markers
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Summary:	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. © 2014 Wiley Periodicals, Inc.
Bibliography:	ark:/67375/WNG-BBP86GP6-L Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq) - No. 300982/2009-7; No. 304678/2012-0 istex:77A3CD5AB1B04711DE61D720436A6FB366A3554A ArticleID:AJMGA36444 Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) - No. 2013/03236-5 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1552-4825 1552-4833
DOI:	10.1002/ajmg.a.36444