Evidence map›Paper›PMID 42265917›Full record

ArticleHGG advances2026

Nanopore-based haplotype-resolved X chromosome inactivation for severity assessment in X-linked disorders: An AIFM1 study with a mosaic PDHA1 carrier.

Kohta Nakamura, Atsuko Okazaki, Daisuke Motooka, Naoyuki Matsumoto, Yuiko Hasegawa, Sayaka Fukuda, Manami Yabe, Ayumu Sugiura, Yukiko Yatsuka, Takuya Fushimi and 5 more

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Article in HGG advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Kohta NakamuraDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Atsuko OkazakiDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan. Electronic address: a-okazaki@juntendo.ac.jp.
Daisuke MotookaDepartment of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Naoyuki MatsumotoDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Yuiko HasegawaDepartment of Medical Genetics, Osaka Women's and Children's Hospital, Osaka, Japan.
Sayaka FukudaDepartment of Neonatal Medicine, Osaka Women's and Children's Hospital, Osaka, Japan.
Manami YabeDepartment of Pediatrics, Nagano Red Cross Hospital, Nagano, Japan; Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Ayumu SugiuraDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Yukiko YatsukaDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Takuya FushimiDepartment of Metabolism, Chiba Children's Hospital, Chiba, Japan.
Takanori OnukiDepartment of Metabolism, Chiba Children's Hospital, Chiba, Japan.
Yuko AidaDepartment of Metabolism, Chiba Children's Hospital, Chiba, Japan.
Akira OhtakeDepartment of Pediatrics and Clinical Genomics, Saitama Medical University, Saitama, Japan.
Kei MurayamaDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan; Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.
Yasushi OkazakiDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan. Electronic address: ya-okazaki@juntendo.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

X chromosome inactivation (XCI) modifies disease severity in females with X-linked variants, but clinically applicable high-resolution assessment remains limited. We report a family with an apoptosis-inducing factor, mitochondria-associated 1 (AIFM1) variant that shows marked intrafamilial phenotypic variability and evaluated whether haplotype-resolved nanopore sequencing can inform clinical interpretation. Targeted long-read sequencing was performed in a severely affected hemizygous male, his asymptomatic heterozygous mother, and a severely affected heterozygous sibling. In the hemizygous male, the sample served as a technical control, with all reads mapping to a single haplotype, consistent with a hemizygous X chromosome. Among heterozygous carriers with the identical variant (c.506C>T [p.Pro169Leu]), XCI correlated with severity: the affected sibling showed 84% skew favoring activation of the pathogenic allele, whereas the mother showed preferential inactivation (20%). This family-based study shows that using nanopore sequencing for haplotype-resolved XCI analysis may provide a practical framework for selected X-linked disorders with variable expressivity.

Indexed as

Apoptosis Inducing FactorGenetic Diseases, X-LinkedHaplotypesX Chromosome InactivationChromosomes, Human, XFemaleHeterozygoteHumansMaleNanoporesNanopore SequencingPedigreeApoptosis Inducing FactorAIFM1clinical predictionlong-read sequencingnanopore sequencingPDHA1X chromosome inactivationXCI skew

Identifiers

PMID42265917
PMCPMC13347936

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LicenceCC BY-NC-ND
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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.