Evidence map›Paper›PMID 40164710›Full record

ReviewJournal of human genetics2025

Hyaluronidase 2 deficiency due to novel compound heterozygous variants in HYAL2: a case report of siblings with HYAL2 deficiency showing different clinical severity and literature review.

Ryuta Orimoto, Eriko Adachi, Maki Gau, Yoko Saito, Haruki Yamano, Hisae Nakatani, Shizuka Kirino, Kengo Moriyama, Yohei Yamaguchi, Tomoko Mizuno and 4 more

Abstract readCase ReportsReview
PubMed Publisher
In one paragraph

Review in Journal of human genetics, 2025. 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
–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

1 citing paper in PubMed.

  1. Functional Analysis ofInternational journal of molecular sciences · 2025
    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

14 authors.

Ryuta OrimotoDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan.
Eriko AdachiDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan.
Maki GauDepartment of Life Science and Bioethics, Institute of Science Tokyo, Tokyo, Japan.
Yoko SaitoDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan.
Haruki YamanoDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan.
Hisae NakataniDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan.
Shizuka KirinoDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan.
Kengo MoriyamaDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan.
Yohei YamaguchiDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan.
Tomoko MizunoDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan.
Taku IshiiDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan.
Masayuki YoshidaDepartment of Life Science and Bioethics, Institute of Science Tokyo, Tokyo, Japan.
Kenichi KashimadaDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan.
Kei TakasawaDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, Tokyo, Japan. ktakasawa.ped@tmd.ac.jp.ORCID http://orcid.org/0000-0001-6947-4034

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study reports the first Asian case of syndromic cleft lip and palate resembling CHARGE-like syndrome, caused by novel compound heterozygous variants of the HYAL2 gene. Hyaluronidase-2 (HYAL2) plays a critical role in hyaluronic acid degradation and tissue remodelling. A 2-year-old Japanese boy presented with growth deficiency, congenital heart disease, craniofacial dysmorphism, micropenis, and developmental delays-features that overlapped with those of CHARGE syndrome. Genetic analysis identified two rare HYAL2 missense variants (c.1133G>A, p.Arg378His; c.1271A>G, p.His424Arg), classified as "likely pathogenic" based on ACMG/AMP criteria. This case highlights the importance of considering HYAL2 deficiency in the syndromic presentation of cleft lip and palate with congenital heart disease, particularly in the absence of CHD7 abnormalities. This study also emphasizes potential primary testicular dysfunction in male patients with HYAL2 deficiency and underscores the need for further research to clarify genotype-phenotype correlations and pathology.

Indexed as

Cell Adhesion MoleculesCleft LipCleft PalateHyaluronoglucosaminidaseChild, PreschoolGenetic Association StudiesGPI-Linked ProteinsHeterozygoteHumansMaleMutation, MissensePhenotypeSiblingsCell Adhesion MoleculesGPI-Linked ProteinsHyal2 protein, humanHyaluronoglucosaminidase

Identifiers

PMID40164710

What OpenQuestion holds

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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.