Evidence map›Paper›PMID 31393562›Full record

ArticleThe Journal of clinical endocrinology and metabolism2019

Mobile DNA in Endocrinology: LINE-1 Retrotransposon Causing Partial Androgen Insensitivity Syndrome.

Rafael Loch Batista, Katsumi Yamaguchi, Andresa di Santi Rodrigues, Mirian Yumie Nishi, John L Goodier, Luciani Renata Carvalho, Sorahia Domenice, Elaine M F Costa, Haig H Kazazian, Berenice Bilharinho Mendonca

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Rafael Loch BatistaUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, da Disciplina de Endocrinologia e Metabologia do Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Katsumi YamaguchiMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Hospital, Baltimore, Maryland.
Andresa di Santi RodriguesUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, da Disciplina de Endocrinologia e Metabologia do Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Mirian Yumie NishiUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, da Disciplina de Endocrinologia e Metabologia do Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
John L GoodierMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Hospital, Baltimore, Maryland.
Luciani Renata CarvalhoUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, da Disciplina de Endocrinologia e Metabologia do Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Sorahia DomeniceUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, da Disciplina de Endocrinologia e Metabologia do Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Elaine M F CostaUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, da Disciplina de Endocrinologia e Metabologia do Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Haig H KazazianMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Hospital, Baltimore, Maryland.
Berenice Bilharinho MendoncaUnidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, da Disciplina de Endocrinologia e Metabologia do Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo · BRJohns Hopkins Hospital · US

Funding

Retrotransposition in Health and DiseaseR01GM099875 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI KAZAZIAN, HAIG H. · 2012 to 2019
$4.0M
Retrotransposition independent LINE 1-induced DNA damage in normal and aging cellsR21AG056840 · NIA · JOHNS HOPKINS UNIVERSITY · PI GOODIER, JOHN LAWRENCE · 2018 to 2019
$450k
NIA NIH HHS R21 AG056840NIGMS NIH HHS R01 GM099875
6 · The paper itself

Abstract

contextAndrogen insensitivity syndrome (AIS) is the most common cause of disorders of sex development in 46,XY individuals. It is an X-linked condition usually caused by pathogenic allelic variants in the androgen receptor (AR) gene. The phenotype depends on the AR variant, ranging from severe undervirilization (complete AIS) to several degrees of external genitalia undervirilization. Although 90% of those with complete AIS will have AR mutations, this will only be true for 40% of those with partial AIS (PAIS).

objectiveTo identify the genetic etiology of AIS in a large multigenerational family with the PAIS phenotype.

participantsNine affected individuals with clinical and laboratory findings consistent with PAIS and a normal exonic AR sequencing. SETTINGS: Endocrine clinic and genetic institute from two academic referral centers.

designAnalysis of whole exons of the AR gene, including splicing regions, was performed, followed by sequencing of the 5'untranslated region (UTR) of the AR gene. Detailed phenotyping was performed at the initial diagnosis and long-term follow-up, and circulating levels of steroid gonadal hormones were measured in all affected individuals. AR expression was measured using RT-PCR and cultured fibroblasts.

resultsAll 46,XY family members with PAIS had inherited, in hemizygosity, a complex defect (∼1100 bp) in the 5'UTR region of the AR surrounded by a duplicated 18-bp sequence (target site duplication). This sequence is 99.7% similar to an active, long, interspersed element present on the X chromosome (AC002980; Xq22.2), which was inserted in the 5'UTR of the AR gene, severely reducing AR expression and leading to PAIS.

conclusionThe molecular diagnosis of PAIS remains challenging. The genomic effect of retrotransposon mobilization should be considered a possible molecular cause of AIS and other AR diseases.

Indexed as

MutationAdolescentAdultAndrogen-Insensitivity SyndromeChildChild, PreschoolChromosomes, Human, XFemaleFollow-Up StudiesHumansInfantLong Interspersed Nucleotide ElementsMalePedigreePhenotypePrognosisAR protein, humanReceptors, Androgen

Identifiers

PMID31393562
PMCPMC6834070
OpenAlexW2967804020

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.