Journal of Human Genetics最新文献

{"title":"Report of a missense TJP2 variant associated to PFIC4 with a pronounced phenotypic variability: Focus on the structural effects on the protein level.","authors":"Boudour Khabou, Houcemeddine Othman, Manel Guirat, Imen Chabchoub, Sana Kmiha, Bahri Mahjoub, Rania Abdelhadi, Afif Ben Mahmoud, Rim Kallel, Tahya Sellami Boudawara, Thouraya Kammoun, Faiza Fakhfakh, Hassen Hadj Kacem, Hassen Kammoun","doi":"10.1038/s10038-025-01338-w","DOIUrl":"https://doi.org/10.1038/s10038-025-01338-w","url":null,"abstract":"<p><p>PFIC4 is a chronic liver disease which cannot be diagnosed based on clinical and biochemical findings with an unpredictable evolution. Here, we reported three consanguineous families with 9 children suffering from intrahepatic cholestasis with low GGT-activity. Three probands were chosen to undergo genetic testing. In silico analyses were conducted to assess the functional impact of the identified variant, along with variants occurring at highly conserved positions within the protein. Additionally, close clinical monitoring was carried. Targeted-NGS sequencing ruled out the diagnosis of PFIC1 and PFIC2. Subsequently, WES allowed the establishment of PFIC4 diagnosis for the three families through the identification of a homozygous TJP2 variant p. Gly532Arg classified as likely pathogenic with a structural damage predicted based on biomolecular modeling and simulation analysis. In-depth in silico analysis of 90 nsSNPs occurring in highly conserved residues in PDZ domains showed 14 ones seems to be relevant in the clinical practice. Clinically, a pronounced phenotypic variability is noted. In conclusion, our study described a homozygous missense PFIC4-related variant with a highlight on the pathogenic power of such types of variants. The clinical evaluation provided information about the importance of close monitoring to prevent liver failure and clarified the unexpected course of PFIC4.</p>","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A random forest-based predictive model for classifying BRCA1 missense variants: a novel approach for evaluating the missense mutations effect.","authors":"Hamed Ka, Maryam Naghinejad, Akbar Amirfiroozy, Mohd Shahir Shamsir, Sepideh Parvizpour, Jafar Razmara","doi":"10.1038/s10038-025-01341-1","DOIUrl":"https://doi.org/10.1038/s10038-025-01341-1","url":null,"abstract":"<p><p>The right classification of variants is the key to pre-symptomatic detection of disease and conducting preventive actions. Since BRCA1 has a high incidence and penetrance in breast and ovarian cancers, a high-performance predictive tool can be employed to classify the clinical significance of its variants. Several tools have previously been developed for this purpose which poorly classify the significance in specific cases. The proposed tools commonly assign a score without providing any interpretation behind it. To reach an accurate predictive tool with interpretation abilities, in this study, we propose BRCA1-Forest which works based on random forest as a well-known machine learning technique for making interpretable decisions with high specificity and sensitivity in variants classification. The method involves narrowing down available options until reaching the final decision. To this end, a set of BRCA1 benign and pathogenic missense variants was collected first, and then, the dataset was prepared based on the effect of each variant on the protein sequence. The dataset was enriched by adding physicochemical changes and the conservation score of the amino acid position as pathogenicity criteria. The proposed model was trained based on the dataset to classify the clinical significance of variants. The performance of BRCA1-Forest was compared to four state-of-the-art methods, SIFT, PolyPhen2, CADD, and DANN, in terms of different evaluation metrics including precision, recall, false positive rate (FPR), the area under the receiver operator curve (AUC ROC), the area under the precision-recall curve (AUC-PR), and Mathew correlation coefficient (MCC). The results reveal that the proposed model outperforms the abovementioned tools in all metrics except for recall. The software of BRCA1-Forest is available at https://github.com/HamedKAAC/BRCA1Forest .</p>","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPD1 deficiency-a rare, overlooked cause of liver disease.","authors":"Necati Emrecan Türk, Serkan Belkaya, Selçuk Teke, Ceyda Tuna Kırsaçlıoğlu, Fatma Tuba Eminoğlu, Tunahan Çalıkoğlu, Aydan Kansu, Zarife Kuloglu","doi":"10.1038/s10038-025-01339-9","DOIUrl":"https://doi.org/10.1038/s10038-025-01339-9","url":null,"abstract":"<p><p>Transient infantile hypertriglyceridemia is one of the diseases that should be considered in case of unexplained elevated liver enzymes, hypertriglyceridemia and hepatosteatosis. We report 2 siblings with novel homozygous variants in the GPD1 gene with transient infantile hypertriglyceridemia. Two siblings born from consanguineous marriage were referred due to hepatomegaly, elevated transaminases and fatty liver. After excluding other possible causes of fatty liver and elevated transaminase levels; whole-exome sequencing (WES) was performed on genomic DNA isolated from the peripheral blood samples of both patients. Whole exome sequencing revealed the identification of a novel homozygous variant, c.628 G > C:p.G210R, in GPD1. Our report underscores the importance of genome sequencing in diagnosing unexplained childhood fatty liver disease and/or elevated enzyme levels. In patients with transient infantile hypertriglyceridemia, investigation into novel homozygous variants in the GPD1 gene should be conducted using whole exome sequencing.</p>","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of MCCC1 expression by a Parkinson's disease-associated intronic variant: implications for pathogenesis.","authors":"Shunsaku Sogabe, Hiroko Nakano, Yusuke Ogasahara, Pei-Chieng Cha, Yuko Ando, Mariko Taniguchi-Ikeda, Ryusaku Matsumoto, Motoi Kanagawa, Kazuhiro Kobayashi, Shigeo Murayama, Takashi Aoi, Tatsushi Toda, Wataru Satake","doi":"10.1038/s10038-025-01335-z","DOIUrl":"https://doi.org/10.1038/s10038-025-01335-z","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuron loss and α-synuclein aggregation. While some familial cases result from single-gene mutations, most are sporadic, involving complex genetic and environmental interactions. Among PD risk loci identified through genome-wide association studies, MCCC1 encodes a mitochondrial enzyme essential for leucine catabolism; however, the causal variant remains unclear. Here, we investigated whether the intronic variant rs12637471 regulates MCCC1 mRNA expression and influences PD risk. Postmortem brain analysis revealed significantly elevated MCCC1 mRNA levels in G-allele carriers, consistent with peripheral tissue eQTL data from GTEx. Using CRISPR/Cas9-edited induced pluripotent stem cells, we generated isogenic lines differing only at rs12637471 and observed increased MCCC1 expression in G-allele dopaminergic neurons. Given MCCC1's mitochondrial role, its dysregulation may impact mitochondrial homeostasis, autophagy, or inflammation, potentially contributing to PD pathogenesis.</p>","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A copy number variant overlapping the 3'UTR of PLP1 causes spastic paraplegia.","authors":"Malak Alghamdi, Essa Alharbi, Salman Aljarallah, Ghaida Alghamdi, Reham M Balahmar, Nisserin Jado, Hebattalah Hamed, Dima Jamjoom, Fahad A Bashiri, Naif A M Almontashiri","doi":"10.1038/s10038-025-01340-2","DOIUrl":"https://doi.org/10.1038/s10038-025-01340-2","url":null,"abstract":"<p><p>Leukodystrophy presents a significant diagnostic challenge due to its varied clinical presentation and similarity to other myelin disorders, characterized by abnormalities in myelin and white matter. Hypomyelination disorders, including Pelizaeus-Merzbacher disease (PMD) and hereditary spastic paraplegias (SPG), are associated with variants in the proteolipid protein 1 (PLP1) gene, leading to symptoms ranging from severe dysmyelination in infancy to delayed dysmyelination and axonal degeneration in adulthood. Family history was taken, and pedigree was constructed. Recruitment included seven males and females with spastic paraplegia and nine healthy relatives, who were clinically investigated, and tested with molecular genetic assays including whole exome sequencing (WES), whole genome sequencing (WGS), and PCR amplification with fragment analysis on gel electrophoresis to identify and confirm the genetic cause. Family history was consistent with hereditary condition marked by progressive spastic paraplegia in 10 family members. Males had early onset and progressive paraplegia, and neurodegenerative conditions, resulting in a decline in the neurocognitive functions. However, in some females, the symptoms manifested later in their 30s-40s, leading to neurodegenerative conditions and spastic paraplegias. A total of 16 family members were available for genetic testing and segregation studies. Initial clinical WES in four members was negative. Next, WGS identified a novel copy number variant (CNV) loss (75.5 kb) involving the 3'UTR of the PLP1 gene in three members (the mother, affected son, but not in the unaffected son). Segregation studies in all 16 family members confirmed the presence of the CNV in five additional affected individuals and an asymptomatic female, but not in the eight asymptomatic individuals. Our study reports a novel 3'UTR CNV in PLP1 in a large family with several individuals affected with SPG. This finding expands the mutational landscape of the PLP1-related diseases to include CNV and, possibly, small sequence changes in the regulatory regions of PLP1, that would otherwise be overlooked during the interpretation of the next generation sequencing data.</p>","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline mosaicism in TCF20-associated neurodevelopmental disorders: a case study and literature review","authors":"Jessie Poquérusse,&nbsp;Whitney Whitford,&nbsp;Juliet Taylor,&nbsp;Nerine Gregersen,&nbsp;Donald R. Love,&nbsp;Bobby Tsang,&nbsp;Kylie M. Drake,&nbsp;Russell G. Snell,&nbsp;Klaus Lehnert,&nbsp;Jessie C. Jacobsen","doi":"10.1038/s10038-025-01323-3","DOIUrl":"10.1038/s10038-025-01323-3","url":null,"abstract":"Autosomal dominant variants in transcription factor 20 (TCF20) can result in TCF20-associated neurodevelopmental disorder (TAND), a condition characterized by developmental delay and intellectual disability, autism, dysmorphisms, dystonia, and variable other neurological features. To date, a total of 91 individuals with TAND have been reported; ~67% of cases arose de novo, while ~10% were inherited, and, intriguingly, ~8% were either confirmed or suspected to have arisen via germline mosaicism. Here, we describe two siblings with a developmental condition characterized by intellectual disability, autism, a circadian rhythm sleep disorder, and attention deficit hyperactivity disorder (ADHD) caused by a novel heterozygous single nucleotide deletion in the TCF20 gene, NM_001378418.1:c.4737del; NP_001365347.1:p.Lys1579Asnfs*36 (GRCh38/hg38). The variant was not detected in DNA extracted from peripheral blood in either parent by Sanger sequencing of PCR-generated amplicons, or by deep sequencing of PCR amplicons using MiSeq and MinION. However, droplet digital PCR (ddPCR) of DNA derived from early morning urine detected the variation in 3.2% of the father’s urothelial cells, confirming germline mosaicism. This report is only the second to confirm with physical evidence TCF20 germline mosaicism and discusses germline mosaicism as a likely under-detected mode of inheritance in neurodevelopmental conditions.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"70 4","pages":"215-222"},"PeriodicalIF":2.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s10038-025-01323-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel FBN1 intron variant causes isolated ectopia lentis via in-frame exon skipping","authors":"Norihiro Shimizu,&nbsp;Yoichi Mashimo,&nbsp;Hirotaka Yokouchi,&nbsp;Yosuke Nishio,&nbsp;Setsu Sawai,&nbsp;Tomohiko Ichikawa,&nbsp;Tomoo Ogi,&nbsp;Takayuki Baba,&nbsp;Yoshihiro Onouchi","doi":"10.1038/s10038-025-01318-0","DOIUrl":"10.1038/s10038-025-01318-0","url":null,"abstract":"Mutations in fibrillin-1 (FBN1) cause various clinical conditions, such as Marfan syndrome (MFS). However, the genotype–phenotype relationships underlying MFS and other conditions relevant to FBN1 mutations have not been fully elucidated. We performed whole-exome sequencing on three participants, including an affected mother–daughter pair, in a three-generation Japanese family with isolated ectopia lentis (IEL). The sequencing identified a novel single-nucleotide variant (c.1327+3A&gt;C) in intron 11 of FBN1 that was shared between the two patients. We confirmed the co-segregation of the variant with IEL in two additional affected relatives in the family. The Combined Annotation-Dependent Depletion score of the variant was 26.1, which was indicated by SpliceAI to influence splicing, with a score of 0.93. Reverse transcription-polymerase chain reaction (RT-PCR) of mRNAs isolated from peripheral blood mononuclear cells revealed aberrant bands in all four affected individuals. Subsequent sequencing revealed that these bands originated from FBN1 transcripts lacking exon 11. The causality of the variant in the skipping of exon 11, which results in an in-frame deletion of 60 amino acids corresponding to the “hinge” region of FBN1 protein, was confirmed in a minigene experiment. Interestingly, the same result was observed for a minigene for c.1327+1G&gt;A, a variant previously identified in two unrelated EL families without MFS manifestations. These results suggest that the c.1327+3A&gt;C mutation in FBN1 likely leads to IEL. The findings expand our knowledge of FBN1 and provide insights into FBN1-related diseases.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"70 4","pages":"199-205"},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s10038-025-01318-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotype puzzle: the role of novel LMBRD1 gene variant in Cbl deficiency causing Dyskeratosis Congenita-like clinical manifestations","authors":"Anjali Shah,&nbsp;Santosh Khuba,&nbsp;Selvaa Kumar C,&nbsp;Chandrakala Shanmukhaiah,&nbsp;Merin George,&nbsp;Somprakash Dhangar,&nbsp;Jagdeeshwar Ghatanatti,&nbsp;Babu Rao Vundinti","doi":"10.1038/s10038-025-01320-6","DOIUrl":"10.1038/s10038-025-01320-6","url":null,"abstract":"Cobalamin (Cbl) metabolism deficiencies are a heterogeneous group (CblA, CblB, CblC, CblD, CblE, CblF, CblG) of autosomal recessive disorders. CblF deficiency occurs due to mutations in LMBRD1 gene, causing variable phenotype, including neurological, haematological, developmental and dermatological defects. Here, we describe a 15-year-old male, presented with clinical features of Dyskeratosis Congenita (DC) such as dystrophic nails, skin discoloration with additional clinical features of uniform reticulate-brown hued hyperpigmentation, developmental delay, mild intellectual disability, mucositis and anemia. Genomic analysis using high throughput next generation sequencing (NGS) identified a novel splice site deletion (c.562+4_562+7del) in the LMBRD1 gene resulting in Cbl deficiency. cDNA sequencing elucidated exon 6 skipping as a consequence of a novel deletion, resulting in significant structural alterations of LMBD1 protein, which was further validated by in-silico computational analysis. Computational modeling and docking studies revealed a reduced interaction affinity between the LMBD1 protein and its partner protein ABCD4. These alterations contribute to a disrupted cascade mechanism in cobalamin (Cbl) metabolism resulting in development of variable clinical phenotypes. In our case, the proband was treated with intravenous hydroxocobalamin therapy and follow up showed a significant improvement in clinical symptoms of skin hyperpigmentation, angular cheilitis and aphthous ulcers. Hence the genomic analysis is essentially important for the appropriate genetic counseling and management of the disease.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"70 4","pages":"207-213"},"PeriodicalIF":2.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel missense pathogenic variants of TMEM53 in an Iranian family with craniotubular dysplasia, Ikegawa type","authors":"Kaitao Ren,&nbsp;Niloofar Pirmarzdashti,&nbsp;Farzad Pakdel,&nbsp;Jinhui Zhu,&nbsp;Wanqi Liu,&nbsp;Lin Wang,&nbsp;Moosa Sadrhosseini,&nbsp;Farzaneh Abassi,&nbsp;Yao Xiong,&nbsp;Jiaqi Han,&nbsp;Lianying Jiao,&nbsp;Gen Nishimura,&nbsp;Takahiro Yamada,&nbsp;Rong Qiang,&nbsp;Long Guo","doi":"10.1038/s10038-025-01319-z","DOIUrl":"10.1038/s10038-025-01319-z","url":null,"abstract":"Craniotubular dysplasia, Ikegawa type (CTDI) is a rare autosomal recessive skeletal dysplasia characterized by hyperostosis of the calvaria and skull base, metadiaphyseal undermodeling of the long tubular bones, and mild shortening and diaphyseal broadening of the short tubular bones. Its causal gene is TMEM53. Six CTDI families have been reported; however, its clinical course and prognosis still remain to be determined. Here, we report two Iranian siblings carrying a novel homozygous missense variant of TMEM53. The affected individuals were referred for progressive severe visual loss of unknown cause. The patient had severe optic atrophy and optic canal narrowing. Radiographic evaluation suggested the diagnosis of CTDI, which was confirmed by the identification of TMEM53 variant (c.704G &gt; T, p.R235L) co-segregating in the consanguineous family. The proband underwent trans-nasal endoscopic optic canal decompression and showed remarkable improvement in visual acuity and daily visual tasks. We recommend early comprehensive clinical and genetic evaluation followed by proper treatment to improve the prognosis of CTDI.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"70 4","pages":"195-198"},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic variants in SHROOM3 associated with hemifacial microsomia","authors":"Qin Li,&nbsp;Bing-Hua Zhang,&nbsp;Qi Chen,&nbsp;Yaoyao Fu,&nbsp;Xiang Zuo,&nbsp;Peng Lu,&nbsp;Weiwei Zhang,&nbsp;Bingqing Wang","doi":"10.1038/s10038-025-01317-1","DOIUrl":"10.1038/s10038-025-01317-1","url":null,"abstract":"Hemifacial microsomia (HFM) is a rare congenital disorder that affects facial symmetry, ear development, and other congenital anomalies. However, known causal genes account for only approximately 6% of patients, indicating the need to discover more pathogenic genes. Association tests demonstrated an association between common variants in SHROOM3 and HFM (P = 1.02E-4 for the lead SNP), while gene burden analysis revealed a significant enrichment of rare variants in HFM patients compared to healthy controls (P = 2.78E-5). We then evaluated the expression patterns of SHROOM3 and the consequences of its deleterious variants. Our study identified 7 deleterious variants in SHROOM3 among the 320 Chinese HFM patients and 2 deleterious variants in two HFM trios, respectively, suggesting a model of dominant inheritance with incomplete penetrance. These variants were predicted to significantly impact SHROOM3 function. Furthermore, the gene expression pattern of SHROOM3 in the pharyngeal arches and the presence of facial abnormalities in gene-edited mice suggest that SHROOM3 plays important roles in facial development. Our findings suggest that SHROOM3 is a likely pathogenic gene for HFM.","PeriodicalId":16077,"journal":{"name":"Journal of Human Genetics","volume":"70 4","pages":"189-194"},"PeriodicalIF":2.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}