Evidence map›Paper›PMID 40346069›Full record

ArticleNPJ genomic medicine2025

Mosaic X-linked adrenoleukodystrophy in males identified by newborn screening and next-generation sequencing.

Alexandra C Keefe, Dana M Jensen, Meranda M Pham, Natalie Y T Au, Erika Beckman, Monica Penon-Portmann, Emily Shelkowitz, Renee Bend, Michelle M Morrow, Paul Kruszka and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ genomic medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

25 authors.

Alexandra C KeefeUniversity of Washington, Department of Pediatrics, Division of Medical Genetics, Seattle, WA, USA. alexandra.keefe@seattlechildrens.org.ORCID http://orcid.org/0009-0009-2455-1687
Dana M JensenSeattle Children's Research Institute, Seattle, WA, USA.
Meranda M PhamSeattle Children's Research Institute, Seattle, WA, USA.
Natalie Y T AuSeattle Children's Research Institute, Seattle, WA, USA.
Erika BeckmanUniversity of Washington, Department of Pediatrics, Division of Medical Genetics, Seattle, WA, USA.
Monica Penon-PortmannUniversity of Washington, Department of Pediatrics, Division of Medical Genetics, Seattle, WA, USA.
Emily ShelkowitzUniversity of Washington, Department of Pediatrics, Division of Medical Genetics, Seattle, WA, USA.
Renee BendPrevention Genetics, Marshfield, WI, USA.
Michelle M MorrowGeneDx, Gaithersburg, MD, USA.
Paul KruszkaGeneDx, Gaithersburg, MD, USA.
Divya VatsKaiser Permanente, Sacramento, CA, USA.
Bianca E RussellUniversity of California, Los Angeles, Department of Human Genetics, Division of Clinical Genetics, David Geffen School of Medicine, Los Angeles, CA, USA.
Erica ChanUniversity of California, Los Angeles, Department of Human Genetics, Division of Clinical Genetics, David Geffen School of Medicine, Los Angeles, CA, USA.
Derek WongUniversity of California, Los Angeles, Department of Human Genetics, Division of Clinical Genetics, David Geffen School of Medicine, Los Angeles, CA, USA.
Ahna RabaniUniversity of California, Los Angeles, Department of Human Genetics, Division of Clinical Genetics, David Geffen School of Medicine, Los Angeles, CA, USA.
Lauren O'GradyDivision of Medical Genetics and Metabolism, Massachusetts General Hospital for Children, Boston, MA, USA.
Inderneel SahaiDivision of Medical Genetics and Metabolism, Massachusetts General Hospital for Children, Boston, MA, USA.
Kimberly WidmeyerDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Ethan D SperryDivision of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Barbara E HallinanDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Rebecca TryonDepartment of Genetics, M Health Fairview, Minneapolis, MN, USA.
Troy C LundDepartment of Pediatrics, Division of Blood and Marrow Transplantation & Cellular Therapy, University of Minnesota Medical School, Minneapolis, MN, USA.
Florian S EichlerDepartment of Neurology, Harvard Medical School, Boston, MA, USA.
Angela SunUniversity of Washington, Department of Pediatrics, Division of Medical Genetics, Seattle, WA, USA.
James T BennettUniversity of Washington, Department of Pediatrics, Division of Medical Genetics, Seattle, WA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Somatic mosaicism produces genetic differences between cells in an individual and is an underrecognized contributor to phenotypic variability. Precise understanding of the natural history of genetic diseases, therefore, requires detection and recognition of low-level mosaicism, which remains technically challenging, particularly for X-linked genes. Here, we identify six males with mosaic X-linked adrenoleukodystrophy (X-ALD), a neurometabolic peroxisomal disorder caused by pathogenic variants in ABCD1 that is currently included in 44 state newborn screening (NBS) programs, and estimate the incidence of somatic mosaicism. Of 227 males from 2 laboratories performing ABCD1 next-generation sequencing, 1.8% (4/227) had pathogenic or likely pathogenic ABCD1 variants that were mosaic. In one mosaic male individual, allele-specific measurements across multiple tissues demonstrated ABCD1 variant allele fractions ranging from 66 to 82%. Our findings have implications for the identification of X-ALD through NBS, and additional studies could provide insight into the pathogenesis and natural history of X-ALD.

Identifiers

PMID40346069
PMCPMC12064771

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.