Evidence map›Paper›PMID 35606856›Full record

ArticleOrphanet journal of rare diseases2022

Phenotype expansion of variants affecting p38 MAPK signaling in hypospadias patients.

Defu Lin, Huakang Du, Sen Zhao, Bowen Liu, Hongcheng Song, Guannan Wang, Weiping Zhang, Haiyan Liang, Pei Liu, Chao Liu and 10 more

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

Article in Orphanet journal of rare diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.7field-weighted citation impact, top 33% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Article
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

20 authors at 4 institutions in 3 countries.

Defu Lin *Department of Urology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
Huakang Du *Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.
Sen Zhao *Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.
Bowen LiuDepartment of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.
Hongcheng SongDepartment of Urology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
Guannan WangDepartment of Urology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
Weiping ZhangDepartment of Urology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
Haiyan LiangDepartment of Urology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
Pei LiuDepartment of Urology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
Chao LiuDepartment of Urology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
Wenwen HanDepartment of Urology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
Zhenwu LiDepartment of Urology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
Yang YangDepartment of Urology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
Shuofan ChenDepartment of Urology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
Lina ZhaoDepartment of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China.
Xiaoxin LiBeijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, 100730, People's Republic of China.
Zhihong WuBeijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, 100730, People's Republic of China.
DISCO (Deciphering Disorders Involving Scoliosis & COmorbidities) study group
Ning Sun *Department of Urology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China. doctorsn@163.com.
Nan Wu *Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People's Republic of China. dr.wunan@pumch.cn.ORCID 0000-0002-9429-2889
Capital Medical University · CNAcademy of Medical Sciences · GBChinese Academy of Medical Sciences & Peking Union Medical College · CNJiangnan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHypospadias is a congenital anomaly of the male urogenital system. Genetics factors play an important role in its pathogenesis. To search for potential causal genes/variants for hypospadias, we performed exome sequencing in a pedigree with three patients across two generations and a cohort of 49 sporadic patients with hypospadias.

resultsA novel BRAF variant (NM_004333.6: c.362C > A) was found to co-segregate with the hypospadias phenotype in the disease pedigree. In cells overexpressing the BRAF mutant, the phosphorylation level of p38 MAPK was significantly increased as compared with the cells overexpressing the wild-type BRAF or RASopathy-related BRAF mutant. This variant further led to a reduced transcription level of the SRY gene, which is essential for the normal development of the male reproductive system. In the cohort of sporadic patients, we identified two additional variants in p38 MAPK signaling-related genes (TRIM67 and DAB2IP) potentially associated with hypospadias.

conclusionOur study expands the phenotypic spectrum of variants affecting p38 MAPK signaling toward the involvement of hypospadias.

Indexed as

HypospadiasProto-Oncogene Proteins B-rafHumansMaleMAP Kinase Signaling Systemp38 Mitogen-Activated Protein KinasesPhenotypePhosphorylationras GTPase-Activating ProteinsDAB2IP protein, humanp38 Mitogen-Activated Protein KinasesProto-Oncogene Proteins B-rafras GTPase-Activating ProteinsHypospadiasMitogen-activated protein kinases (MAPK)p38 mitogen-activated protein kinasesPedigreeProto-oncogene proteins B-raf (BRAF)Sex-determining region Y protein (SRY)

Identifiers

PMID35606856
PMCPMC9128137
OpenAlexW4281289186

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.