Evidence map›Paper›PMID 27661448›Full record

ArticleOphthalmic genetics

Two missense mutations in SALL4 in a patient with microphthalmia, coloboma, and optic nerve hypoplasia.

E Ullah, D Wu, L Madireddy, R Lao, P Ling-Fung Tang, E Wan, T Bardakjian, S Kopinsky, P-Y Kwok, A Schneider and 3 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Ophthalmic genetics. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.2field-weighted citation impact, top 16% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Genetic disruption of zebrafish mab21l1 reveals a conserved role in eye development and affected pathways.Developmental dynamics : an official publication of the American Association of Anatomists · 2021
    Article
  3. Article
  4. Article
  5. Review
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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

13 authors at 3 institutions in 2 countries.

E Ullaha Department of Pediatrics , University of California, San Francisco , San Francisco , California , USA.
D Wua Department of Pediatrics , University of California, San Francisco , San Francisco , California , USA.
L Madireddyc Department of Neurology , University of California, San Francisco , San Francisco , California , USA.
R Laod Cardiovascular Research Institute , University of California, San Francisco , San Francisco , California , USA.
P Ling-Fung Tangd Cardiovascular Research Institute , University of California, San Francisco , San Francisco , California , USA.
E Wand Cardiovascular Research Institute , University of California, San Francisco , San Francisco , California , USA.
T Bardakjiane Division of Medical Genetics , Einstein Healthcare Network , Philadelphia , Pennsylvania , USA.
S Kopinskye Division of Medical Genetics , Einstein Healthcare Network , Philadelphia , Pennsylvania , USA.
P-Y Kwokd Cardiovascular Research Institute , University of California, San Francisco , San Francisco , California , USA.
A Schneidere Division of Medical Genetics , Einstein Healthcare Network , Philadelphia , Pennsylvania , USA.
S Baranzinic Department of Neurology , University of California, San Francisco , San Francisco , California , USA.
M Ansarb Department of Biochemistry, Faculty of Biological Sciences , Quaid-i-Azam University , Islamabad , Pakistan.
A Slavotineka Department of Pediatrics , University of California, San Francisco , San Francisco , California , USA.
University of California, San Francisco · USEinstein Healthcare Network · USQuaid-i-Azam University · PK

Funding

Gene Discovery in Human Anopthalmia/MicropthalmiaR21EY022779 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SLAVOTINEK, ANNE M. · 2012 to 2013
$421k
Anopthalmia Spectrum DisordersR21EY019999 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SLAVOTINEK, ANNE M. · 2010 to 2011
$417k
NEI NIH HHS R21 EY019999NEI NIH HHS R21 EY022779
6 · The paper itself

Abstract

To investigate the genetic etiology of anophthalmia and microphthalmia, we used exome sequencing in a Caucasian female with unilateral microphthalmia and coloboma, bilateral optic nerve hypoplasia, ventricular and atrial septal defects, and growth delays. We found two sequence variants in SALL4 - c.[575C>A], predicting p.(Ala192Glu), that was paternally inherited, and c.[2053G>C], predicting p.(Asp685His), that was maternally inherited. Haploinsufficiency for SALL4 due to nonsense or frameshift mutations has been associated with acro-renal ocular syndrome that is characterized by eye defects including Duane anomaly and coloboma, in addition to radial ray malformations and renal abnormalities. Our report is the first description of structural eye defects associated with two missense variants in SALL4 inherited in trans; the absence of reported findings in both parents suggests that both sequence variants are hypomorphic mutations and that both are needed for the ocular phenotype. SALL4 is expressed in the developing lens and regulates BMP4, leading us to speculate that altered BMP4 expression was responsible for the eye defects, but we could not demonstrate altered BMP4 expression in vitro after using small interfering RNAs (siRNAs) to reduce SALL4 expression. We conclude that SALL4 hypomorphic variants may influence eye development.

Indexed as

Mutation, MissenseColobomaExomeFemaleGrowth DisordersHeart Septal DefectsHumansInfantMicrophthalmosOptic Nerve DiseasesPedigreePhenotypePolymerase Chain ReactionSequence Analysis, DNATranscription FactorsSALL4 protein, humanTranscription FactorsAnophthalmiaBMP4colobomamicrophthalmiaSALL4

Identifiers

PMID27661448
PMCPMC6238016
OpenAlexW2521179395

What OpenQuestion holds

Textmetadata
LicenceTDM
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.