He et al. BMC Pediatrics(2024) 24:517
https://doi.org/10.1186/s12887-024-04991-w

BMC Pediatrics

CASE REPORTOpen Access

Philadelphia chromosome-like acutelymphoblastic leukemia with concomitantrearrangements of CRLF2 and ABL1: a pediatriccase report
Guo-qian He1,2, Yu-peng Lei1,2, Duo-wen Huang1,2, Ju Gao1,2 and Rong Yang1,2*
Abstract
Background BCR::ABL1-like or Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) was firstreported in 2009. Ph-like ALL is characterized by gene signature similar to Philadelphia chromosome ALL, but without
BCR::ABL1 fusions. Molecularly, Ph-like ALL is divided into seven categories, with CRLF2 and ABL-class rearrangements
being the two most common subtypes, exhibiting alterations in distinct downstream signaling cascades.
Case presentation We report a rare case of pediatric Ph-like ALL with concomitant CRLF2 and ABL1 rearrangements.
CRLF2 was fused with P2RY8, its most common fusion partner, whereas ABL1 was fused with MYO18B, a novel
fusion partner that has not been previously reported. The 4-year-old female patient was treated using the national
multicenter CCCG-ALL-2020 protocol with the addition of dasatinib at the end of induction when ABL1 rearrangement
was confirmed by RNA-seq. Morphologically and molecularly, the patient remained in continuous remission until thelast follow-up. To the best of our knowledge, this is the first case of Ph-like ALL harboring two distinct rearrangement
categories.
Conclusions Our results identified that ABL1 rearrangement and CRLF2 rearrangement can coexist. The applicationof FISH, whole transcription sequencing, PCR can help us to have a more comprehensive understanding of ALL
cytogenetics and molecular biology. Further studies are needed to explore the role of targeted therapies in such rareclinical scenarios.
Keywords Acute lymphoblastic leukemia, Philadelphia chromosome-like, CRLF2, ABL1, MYO18B, Case report*Correspondence:
Rong Yang
267278329@qq.com
1
Key Laboratory of Birth Defects and Related Diseases of Women andChildren, West China Second University Hospital, Ministry of Education,
Sichuan University, Chengdu, China
2
Department of Pediatrics, West China Second University Hospital,
Sichuan University, Chengdu, China© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you
give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified thelicensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to thematerial. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation
or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://
creativecommons.org/licenses/by-nc-nd/4.0/.

He et al. BMC Pediatrics(2024) 24:517

Background
BCR::ABL1-like or Philadelphia chromosome-like (Phlike) acute lymphoblastic leukemia (ALL) is characterized by a poor early treatment response, high recurrence
rate, and unfavorable clinical outcomes. The 5-year EFS/DFS of children Ph-like ALL varied widely across regions,
ranging from around 30–90%. The 5-year EFS of adults
Ph-like ALL were about 24% [1]. Ph-like ALL cases mostcommonly present with CRLF2 or ABL class rearrangements [2, 3]; however, Ph-like ALL with concomitantrearrangements of both CRLF2 and ABL1 has not been
identified previously. Here, we report a rare pediatriccase of Ph-like ALL with concomitant CRLF2 and ABL1
rearrangements. CRLF2 was fused with P2RY8, the mostcommon fusion partner, whereas ABL1 was fused with
MYO18B, a novel fusion partner that has not been previously reported. Studies have shown that ABL-classrearranged ALL has a good therapeutic response to thetyrosine kinase inhibitors (TKI) imatinib or dasatinib[4–8], similar to Ph positive ALL. However, effective
therapies for CRLF2 rearrangements are still under investigation. With the combination of chemotherapy anddasatinib, the patient has remained measurable residual
disease (MRD)-negative for 18 months since therapy
initiation.
Case presentation
A 4-year-old female was admitted to our hospital withintermittent fever and bilateral preauricular masses thatpersisted for 16 days. Approximately 16 days before
admission, the painless preauricular lumps had grownsteadily. Concomitantly, the patient presented withintermittent fever, exhibiting a maximum temperatureof 38.8 °C. Her temperature normalized after intravenous penicillin administration at a local hospital. Before
admission, the patient had no symptoms such as weariness, epistaxis, skin bleeding, or ostealgia. However,three kilograms of body weight were lost in the two
weeks prior to admission. The patient had no history ofillness. The patient had no specific personal and family
history of similar illnesses. On admission, she was in a
relatively stable condition but appeared pale. The size ofthe left preauricular was 2 by 2 cm and right preauricular
was 2.5 by 2.5 cm, exhibiting moderate texture and was
not tender. Abdominal palpation revealed hepatomegaly
and splenomegaly 5 and 7 cm below the ribs, respectively.
Physical examinations of the heart, lungs, and nervous
system revealed negative results. White blood cell count
was 5.4 × 109/L, lymphocytes were 51%, neutrophils were19%, monocytes were 1%, blast cells were 25%, hemoglobin was 63 g/L, platelets were 36 × 109/L, reticulocytes were 0.14%, and absolute reticulocyte count was
0.0045 × 109/L on the complete blood count. Blood biochemical testing revealed normal renal function; alanine

Page 2 of 9aminotransferase 42 U/L; aspartate aminotransferase 18
U/L; lactate dehydrogenase 157 U/L; and normal bloodelectrolyte levels. The results from the disseminatedintravascular coagulation were normal. DNA tests for
Epstein-Barr virus and Cytomegalovirus were negative.
Abdominal ultrasonography revealed an enlarged liverand spleen. ALL was suspected based on a bone marrowsmear, and the French-American-British classification
was L2, with 88.5% lymphoblasts.
Pre-B ALL was identified by bone marrow flow
cytometry based on the expression of CD19, cCD79a,
CD22, CD10, TDT, CD34, HLA-DR, CD9, CD66c,
and CD38, and lack of expression of CD3 or MPO. A
positive MYO18B::ABL1 fusion gene (Fig. 1A), positive
P2RY8::CRLF2 fusion gene (Fig. 1B), positive PTPN11
mutation (E76G, mutation frequency 31.2%), and positive
ETV6 mutation (R105*, mutation frequency 1.6%) wereidentified using whole-transcriptome sequencing. The
MYO18B::ABL1 fusion was verified by polymerase chain
reaction (PCR) and sanger sequencing (Fig. 2). With
positive rates of 49% and 85%, respectively, the ABL1
and CRLF2 probes demonstrated signal separation using
fluorescence in situ hybridization (FISH) (Fig. 3). The
probes used to detect the ABL1 break site were locatedat 9q34.12 and the CRLF2 break site were located at
Xp22.33. CRLF2 overexpression was also observed, withan expression percentage of 99.4%. 47, XX, + 21[2]/47,
idem,?t(1;9)(p34;q34),del [22](q11)[6]/46, XX[12] werethe chromosomal karyotypes found. Analysis of karyotype results can sometimes be inaccurate and subjective, and our karyotype results suggest abnormalities of
9q.34 and 22q. ABL1 is located at 9q.34 and MYO18B
is located at 22q. No IKZF1 gene deletions were foundusing multiplex ligation-dependent probe amplification.
The methods and materials used for this patient’s assay
are provided in the Supplementary Materials.
Combined with the typical clinical signs and symptomsof the patient, the laboratory examination, especially thebone marrow morphology and genetic examination, confirmed the diagnosis of ALL beyond doubt. Based on the
FISH and whole-transcriptome test results, we concluded
that the child was Ph-like ALL.
Acute Lymphoblastic Leukemia-2020, an ongoing project of the China Children’s Cancer Group,
was used to treat the patient once ALL was confirmed (CCCG-ALL-2020; www.chictr.org.cn; Dateof registration: August 5, 2020; Registration number:
ChiCTR2000035264). On day 6 after chemotherapy,
the enlarged lymph nodes were no longer palpable, andon day 18, the enlarged liver was restored to its normal
size. Following chemotherapy, routine complete bloodcount revealed that the red blood cells, white blood
cells, and platelets in the peripheral blood were all stabilized around day 28. A satisfactory response to earlyHe et al. BMC Pediatrics(2024) 24:517

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Fig. 1 A positive MYO18B-ABL1 fusion gene and a positive P2RY8-CRLF2 fusion gene were suggested by whole-transcriptome sequencing. Diagram of
the MYO18B/ABL1 fusion gene. The fracture point of MYO18B is located at chr22:26251330, and the fracture point of ABL1 is located on chr9:133738150,
respectively. Diagram of the P2RY8-CRLF2 fusion gene. The fracture point of P2RY8 is located on chrX:1,655,814, and the fracture point of CRLF2 is locatedon chrX:1,321,529, respectively

He et al. BMC Pediatrics(2024) 24:517

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Fig. 2 Sanger sequencing and PCR electrophoresis of MYO18B/ABL1. (A) Sanger sequencing peak figure of MYO18B/ABL1. The fusion gene sequence is​
G​C​A​G​C​G​G​G​A​G​G​C​A​G​A​G​G​C​C​A​G​C​C​G​G​C​G​G​T​G​C​A​T​G​G​A​G​C ​T ​T​C ​T​A​C​G​T​C ​T​C​C ​T​C​C​G​A​G​A​G​C​C​G​C ​T ​T​C​A​A​C​A​C​C​C ​T​G​G​C​C​G​A​G [GC]. (B) PCR electrophoresis showsthat lane 3 is the PCR product of MYO18B-ABL1 while lane 4 is the negative control

chemotherapy was indicated on day 19 following chemotherapy, when the bone marrow smear showed complete
remission and the flow cytometry (FCM)-MRD was lessthan 0.01%. On day 46, RT-PCR showed negative results
for the MYO18B::ABL1 and P2RY8::CRLF2 fusion genes,
and Sanger sequencing showed negative results for
PTPN11 and ETV6 mutations. On day 28 of induction
therapy, targeted therapy with dasatinib (80 mg/m2/day)
was initiated. The patient developed severe serous cavity
effusions and shortness of breath approximately 10 days
after oral delivery. We immediately discontinued dasatinib, and these symptoms gradually improved. Fourteendays after discontinuation of dasatinib, a reduced doseof dasatinib (60 mg/m2/day) was re-administered at the
beginning of consolidation therapy and continued until
the end of consolidation therapy. At the beginning ofcontinuous treatment, approximately four months after
the initial treatment, we attempted to adjust the dose ofdasatinib to 80 mg/m2/day, and the patient had no further adverse reactions.
It has been 18 months since the initiation of chemotherapy. Every four months, bone marrow smears, FCMMRD, fusion gene qualification, and gene mutation
quantification were performed, with consistently negative results (Fig. 4).

He et al. BMC Pediatrics(2024) 24:517

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Fig. 3 FISH detection indicates signal separation in both ABL1 and CRLF2 (indicated by the white arrow). The ABL1 separation probe showed signal
separation with a positive rate of approximately 49%, while the CRLF2 separation probe showed an abnormal signal mode with a positive rate of approximately 85%

Fig. 4 The treatment timeline of the patient. On day 28 of the induction therapy, targeted therapy of dasatinib (80 mg/m2/day) was added. The patient
had severe serous cavity effusions and shortness of breath approximately 10 days after oral delivery. We immediately stopped the dasatinib administration and these symptoms gradually abated. Fourteen days after dasatinib was discontinued, a reduced dose of dasatinib (60 mg/m2/day) was added
again at the beginning of the consolidation therapy and continued until the end of the consolidation therapy. Complete response at the genetic level ofthe bone marrow was achieved from 19 days after chemotherapy. DAS: dasatinib

Discussion and conclusions
BCR::ABL1-like or Ph-like ALL was first reported in 2009
[9, 10]. Ph-like and Ph + ALL have similar gene expression profiles and are both likely to be complicated bygene mutations in IKZF1, transcription factor 3 (E2A),
early B-cell factor, and paired box 5 [5, 11, 12]. Mutations in PTPN11 and ETV6 were also detected in ourpatient. According to the literature, both PTPN11 andETV6 mutations are common genetic lesions in Ph-like
ALL [13–15]. Similar to BCL::ABL1-positive ALL, theprognosis of Ph-like ALL is worse than that of othertypes of B-cell precursor-ALL. According to the WHO
classification of lymphopoietic tumors updated in 2022,

Ph-like ALL is classified as a recurrent genetic abnormality of B-cell lymphoblastic leukemia/lymphoma [16] andis characterized by a poor early treatment response, highrecurrence rate, and unfavorable clinical outcome.
The incidence of Ph-like ALL gradually increases withage and is approximately 10–15% in children, 20% in adolescents, and 20–27% in adults [5, 17, 18]. Ph-like ALL is
more common in male patients. The male-to-female ratio
is approximately 1.5:1 in children and 4:1 in adults [5]. In
the CCCG-ALL-2020 protocol, methods used to screen
for Ph-like ALL include PCR, FISH, and RNA-seq. These
three methods are routine tests for all patients with ALL,according to our protocol.

He et al. BMC Pediatrics(2024) 24:517

Poor prognosis of patients with Ph-like ALL is associated with genetic abnormalities at the molecular level.
The molecular biological abnormalities of Ph-like ALL
mainly involve kinase and cytokine receptor activation.
The kinase genes and cytokine receptors involved canbe divided into the following major categories: CRLF2
rearrangement, ABL-class rearrangement (ABL1, ABL2,
CSF1R, PDGFRA, and PDGFRB), JAK2 rearrangement,
EPOR rearrangement, JAK/STAT aberrations (TSLP,
IL2RB, and TYK2), RAS pathway mutations (KRAS,
NRAS, NF1, PTPN11, CBL1, and BRAF), and othertypes of genetic abnormalities (NTRK3, PTK2B, BLNK,
FLT3, FGFR1, DGKH) [2, 19, 20]. In addition, it has
been reported that patients with positive ETV6::RUNX1,
TCF3::PBX1, KMT2A-r, and BCR::ABL1 rearrangements
usually do not have the above gene changes of Ph-like
ALL simultaneously [21, 22].
Among the above categories, CRLF2 rearrangement is
the most common genetic abnormality in Ph-like ALL
at all ages, accounting for approximately 40–60% ofcases [5]. The CRLF2 gene is located at Xp22.3 (OMIM:*300357)/Yp11.3 (OMIM: *400023), encoding the thymic stromal lymphopoietin receptor, which binds withthe ligand of the α-chain heterodimer IL-7R to mediate
the downstream signal transduction of lymphogenesis,
anaphylaxis, and inflammation [23]. The vast majority of CRLF2 rearrangements have positive IGH::CRLF2
and P2RY8::CRLF2 fusion genes, and a few have CRLF2
point mutations [24–27]. Approximately 50–60% of
patients with CRLF2 rearrangements are complicated bygenetic abnormalities of the JAK or RAS pathways, suchas NRAS, KRAS, PTPN11, and NF1, and often have lossof heterozygosity (LOH) of IKZF1 and iAMP21. CRLF2
rearrangements are also found in non-Ph-like ALL, specifically in Down Syndrome-associated ALL [28]. CRLF2
overexpression is associated with high MRD during early
treatment and poor outcomes in high-risk ALL [29–31].
We carefully considered whether the JAK inhibitor ruxolitinib should be administered to our patient. Overall,
ruxolitinib efficacy in patients with CRLF2-rearranged
ALL remains unclear. Clinical studies on the ruxolitinibin patients with CRLF2 rearrangement ALL are limited,with only a small number of ongoing clinical trials inchildren and adults with Ph-like ALL (NCT02723994,
NCT03571321, NCT03117751, NCT02420717, and
NCT02723994) and a recently initiated European trial(EudraCT number 2020-005017-41). However, the final
findings have not yet been published. Ruxolitinib isprimarily used as an adjuvant treatment for ALL withabnormalities in JAK2 or the JAK-STAT pathways. RNAseq clearly showed that there were no genetic aberrationsin any genes in the JAK-STAT signaling pathway in ourpatient, and we presumed that the off-label use of ruxolitinib would not provide additional benefits. In addition, it

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has been suggested that P2RY8::CRLF2 could represent
a secondary event because this fusion can be found concomitantly with other subtype-defining alterations such
as iAMP21 or hyperdiploid ALL. In patients with ABL
rearrangement, perhaps ABL1 fusion is more likely to be
the key driver also [32–34].
The downstream signaling pathways JAK/STAT and
P13K/AKT/MTORC1 were abnormally activated in
CRLF2-rearranged cell lines. In IGH::CRLF2-positive celllines, activation of the MTORC1 and RAS pathways plays
a crucial role in their survival, but the survival of CRLF2rearranged cell lines does not depend on JAK activation[35]. The MEK inhibitor trametinib and Akt inhibitor
MK2206 have been shown to enhance the sensitivity of
CRLF2-rearranged cell lines to hormones [36]. Moreover, the combined use of trametinib and gilteritinib cansimultaneously inhibit MEK (RAS pathway) and receptor
tyrosine kinases (RTKs) (P13K/AKT/MTORC pathway),
playing an inhibitory role in CRLF2-rearranged cell lines[37].
ABL class rearrangement is also a common genetic
abnormality in Ph-like ALL, accounting for approximately 10% of all Ph-like ALL cases. Children with
Ph-like ALL have a higher proportion of ABL class rearrangements than adults [5]. Studies have shown that ABLclass-rearranged ALL has a good therapeutic response
to imatinib or dasatinib [4–8], similar to the response
in patients with Ph + ALL. At present, many clinical trials have evaluated the efficacy and safety of dasatinib(ClinicalTrial.gov: NCT 02420717, NCT02883049,
NCT03564470, and NCT02143414). Using the CCCGALL-2015 regimen, our randomized controlled study
confirmed that dasatinib was significantly superior to
imatinib in reducing recurrence in the bone marrow andcentral nervous system without increasing adverse reactions [8]. Therefore, in the CCCG-ALL-2020 regimen,
dasatinib is recommended as the preferred drug for thetargeted therapy of ABL-class Ph-like ALL.
A total of 13 ABL1 partner genes have been reported
to date; however, the partner gene MYO18B (myosinXVIIIb) identified in this case has not been previously
reported [1, 3, 19]. MYO18B (OMIM, *607295) is locatedat 22q12.1. LOH of 22q and is common in patientswith lung, ovarian, and colorectal cancers, suggesting that a tumor suppressor gene may be in this region.
The research results of Nishioka et al. showed that thedeletion, mutation, promoter methylation, and histone
deacetylation of MYO18B in 22q lead to the reduction or
inactivation of MYO18B activity, which is closely related
to the occurrence of lung, ovarian, and colorectal cancers [38–42]. The low expression of MYO18B has beenreported to be related to the poor prognosis of squamouscell carcinoma of the skin [43]. Therefore, MYO18B iscurrently considered a tumor suppressor gene.

He et al. BMC Pediatrics(2024) 24:517

Ph-like ALL with a positive MYO18B::ABL1 fusion
gene has not yet been reported. To our knowledge, this is
the first report of an MYO18B::ABL1 fusion gene in ALL.
Because of the fusion of MYO18B and ABL1, the activityof MYO18B may be reduced. In this case, the 3’ breakpoint of ABL1 was at chr9:133738150 (GRCh38), which
is a common breakpoint of ABL1 and can affect the function of ABL1. Therefore, we speculate that the formationof the MYO18B::ABL1 fusion gene may have been related
to the occurrence of leukemia in this case. In addition,other genetic abnormalities relevant to the pathogenesis of leukemia were detected in our patient, including
P2RY8::CRLF2 fusion gene-positivity, and mutations in
PTPN11 and ETV6. We believe that these genetic abnormalities are potential therapeutic targets for our patient.
CRLF2 and ABL-class rearrangements are the two mostcommon Ph-like ALL subtypes. To the best of our knowledge, patients with ALL featuring both CRLF2 and ABL1
rearrangements are rare. An adult patient with chronic
myelogenous leukemia was reported to be BCR::ABL1positive at initial diagnosis and presented with a new
CRLF2 rearrangement during the B-lymphoblast phase[44]. Both FISH and RNA-seq in this case confirmed
simultaneous CRLF2 and ABL1 rearrangements.
For patients with both CRLF2 and ABL-class rearrangements, it is also necessary for clinicians to consider
the selection of reasonable targeted therapeutic drugs.
In our report, our patient was treated with dasatinib in
combination with chemotherapy, which mainly resulted
for the following reasons. First, the targeting effect ofdasatinib in ABL-class Ph-like ALL has been confirmed
in several studies [1, 45, 46]. In addition, no clinicallyeffective CRLF2-targeted drug is currently available.
Third, after the induction therapy, flow cytometry of thebone marrow on day 19 showed that the FCM-MRD of
the child was < 0.01%, suggesting a good early therapeutic response. Therefore, we selected dasatinib, which has
a proven efficacy against ABL-class ALL, for targeted
therapy. Moreover, guided by FCM-MRD and fusiongene PCR monitoring, post-chemotherapy follow-up andbone marrow monitoring were performed. At present,
13 months after chemotherapy, the bone marrow smear,
FCM-MRD, MYO18B::ABL1, and P2RY8::CRLF2 genes ofthe patient remain negative. We plan to regularly monitor and follow up on the bone marrow characteristics ofthe patient.
Whether children with Ph-like ALL require hemopoietic stem cell transplantation (HSCT) is a matter ofconcern for clinicians. At present, it is believed that chemotherapy combined with TKI can be considered forpatients with continuously negative FCM-MRD results
after induction therapy; however, the bone marrowsmear, FCM-MRD, and genetic examination of children
should be closely monitored. However, for children with

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Ph-like ALL whose FCM-MRD is not negative and highrisk patients with a 5-year disease-free survival of < 30%,
HSCT may be needed [47]. Currently, the long-term
relapse rate in patients with negative bone marrow FCMMRD results prior to HSCT is relatively low. Therefore,
it is recommended that combining chemotherapy with
TKIs or administration of CAR-T cells to achieve bonemarrow FCM-MRD negativity is recommended before
HSCT [48]. After HSCT, it is also necessary to continuously monitor MRD and continue the oral administrationof TKIs. However, the optimal course of TKI treatment
after transplantation remains unclear. Some studies suggest that TKI withdrawal may be considered in patientswith persistently negative MRD for 6 months to one year
after HSCT [49, 50].
Overall, the incidence of Ph-like ALL in children islow; however, the prognosis for this specific malignancy
is poor. Due to the extensive application in recent yearsof next-generation sequencing in clinical practice, morecases of Ph-like ALL have been reported. At present, only
the ABL-class has TKIs as approved treatments. In contrast, targeted therapies for CRLF2 rearrangements, andother types of Ph-like ALL need to be evaluated in additional trials. More research and exploration are neededon the indications for HSCT in children with Ph-like ALL
and whether they would benefit from HSCT.
Abbreviations
BCR	Breakpoint cluster region
MYO18B	Myosin-XVIIIb
CRLF2	Cytokine receptor-like factor 2
P2RY8	Pyrimidinergic receptor p2y, g protein-coupled,8
IGH	Immunoglobulin heavy chain
PTPN11	Protein-tyrosine phosphatase, nonreceptor-type, 11
ETV6	ETS variant transcription factor 6
IKZF1	Ikaros family zinc finger 1ALL	Acute lymphoblastic leukemia
FISH	Fluorescence in situ hybridization
FCM	Flow cytometry
PCR	Polymerase chain reaction
MRD	Measurable residual disease
LOH	Loss of heterozygosity
CCCG-ALL-2020	China Children’s Cancer Group Acute Lymphoblastic
Leukemia 2020
HSCT	Hemopoietic stem cell transplantation
TKI	Tyrosine kinase inhibitors
CAR-T	Chimeric antigen receptor T cell
DAS	Dasatinib

Supplementary Information

The online version contains supplementary material available at https://doi.
org/10.1186/s12887-024-04991-w.
Supplementary Material 1
Supplementary Material 2
Acknowledgements
The authors are grateful to the patient and her family in this study for her
collaboration.

He et al. BMC Pediatrics(2024) 24:517

Author contributions
He GQ and Lei YP wrote the manuscript with contributions from all otherauthors; Huang DW drafted and revised the paper. Gao J and Yang R
performed the topic selection, designed the study and edited the manuscript.
All authors contributed to and reviewed the final manuscript.
Funding
This study was funded by the Sichuan Science and Technology Program,
grant no. No.2022YFS0236, and the Clinical Research Program of Sichuan Anticancer Association (Qilu), grant no.XH2022-507.
Data availability
Sequence data that support the findings of this study have been deposited in
the Sequence Read Archive with the primary accession code PRJNA1000109.

Declarations
Ethics approval and consent to participate
This study was approved by the Ethics Committee of West China Second
Hospital, Sichuan University. The patient’s parents were informed andconsented to participate.
Consent for publication
Written informed consent was obtained from the parents for the publicationof any potentially identifiable images or data included in this article.
Competing interests
The authors declare no competing interests.
Received: 30 November 2023 / Accepted: 1 August 2024

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