European journal of medical genetics最新文献

{"title":"Jaberi-Elahi syndrome: Exploring a novel GTPBP2 mutation and a literature review","authors":"Jamal Manoochehri ,&nbsp;Amirmasoud Shiri ,&nbsp;Somayeh Khoddam ,&nbsp;Maryam Aghasipour ,&nbsp;Neda Kamal ,&nbsp;Hossein Jafari Khamirani ,&nbsp;Seyed Alireza Dastgheib ,&nbsp;Mehdi Dianatpour ,&nbsp;Seyed Mohammad Bagher Tabei","doi":"10.1016/j.ejmg.2024.104953","DOIUrl":"10.1016/j.ejmg.2024.104953","url":null,"abstract":"<div><p>Jaberi-Elahi syndrome is an extremely rare genetic disease caused by pathogenic variants in <em>GTPBP2</em>. The core symptoms of this disease are intellectual disability, motor development delay, abnormal reflexes, skeletal abnormalities, and visual impairment. In this study, we describe a three-year-old girl with a novel homozygous variant in GTPBP2 and a phenotype overlapping with Jaberi-Elahi syndrome. This variant (NM_019096.5:c.1289T &gt; C, p.Leu430Pro) was identified by Whole Exome Sequencing and confirmed by Sanger sequencing although remains classified as VUS based on ACMG criteria. The proband demonstrated motor and intellectual developmental delay, muscle weakness, language disorder, facial dysmorphism, and poor growth. Hitherto, twenty-seven individuals with Jaberi-Elahi syndrome have been reported in the literature. This study, describes a review of the symptoms related to the Jaberi-Elahi syndrome. A large numbers of patients manifest motor development delay (26/28), sparse hair (26/28), and speech disorder (24/28). Moreover, a significant fraction of patients suffer from intellectual disability (23/28), hypotonia (23/28), skeletal problems (23/28), and visual impairment (18/28). In spite of previous patients, the proband in this study did not exhibit any skeletal abnormalities. In summary, we present evidence implicating a novel missense variant in Jaberi-Elahi syndrome, expanding and refining the genetic spectrum of this condition.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104953"},"PeriodicalIF":1.6,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000454/pdfft?md5=fa2a93a0f1d716b2b1a280c4b4a6d038&pid=1-s2.0-S1769721224000454-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing diagnostic gaps and priorities of the global rare diseases community: Recommendations from the IRDiRC diagnostics scientific committee","authors":"David R. Adams ,&nbsp;Clara D.M. van Karnebeek ,&nbsp;Sergi Beltran Agulló ,&nbsp;Víctor Faùndes ,&nbsp;Saumya Shekhar Jamuar ,&nbsp;Sally Ann Lynch ,&nbsp;Guillem Pintos-Morell ,&nbsp;Ratna Dua Puri ,&nbsp;Ruty Shai ,&nbsp;Charles A. Steward ,&nbsp;Biruté Tumiene ,&nbsp;Alain Verloes ,&nbsp;members of the IRDiRC Diagnostic Scientific Committee","doi":"10.1016/j.ejmg.2024.104951","DOIUrl":"10.1016/j.ejmg.2024.104951","url":null,"abstract":"<div><p>The International Rare Diseases Research Consortium (IRDiRC) Diagnostic Scientific Committee (DSC) is charged with discussion and contribution to progress on diagnostic aspects of the IRDiRC core mission. Specifically, IRDiRC goals include timely diagnosis, use of globally coordinated diagnostic pipelines, and assessing the impact of rare diseases on affected individuals. As part of this mission, the DSC endeavored to create a list of research priorities to achieve these goals. We present a discussion of those priorities along with aspects of current, global rare disease needs and opportunities that support our prioritization. In support of this discussion, we also provide clinical vignettes illustrating real-world examples of diagnostic challenges.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104951"},"PeriodicalIF":1.6,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000430/pdfft?md5=2e532883a0ea7819f7f5b17d01630ce4&pid=1-s2.0-S1769721224000430-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a pathogenic deep intronic variant in ATRX ends a diagnostic odyssey","authors":"Jasper J. van der Smagt ,&nbsp;Angeliki P. Lampri ,&nbsp;Iris de Lange ,&nbsp;Mariëlle Alders ,&nbsp;Michiel L. Houben ,&nbsp;Marco J. Koudijs ,&nbsp;Richard H. van Jaarsveld","doi":"10.1016/j.ejmg.2024.104949","DOIUrl":"10.1016/j.ejmg.2024.104949","url":null,"abstract":"<div><p>Variation in the non-coding genome is being increasingly recognized to be involved in monogenic disease etiology. However, the interpretation of non-coding variation is complicated by a lack of understanding of how non-coding genetic elements function. Additional lines of evidence are therefore needed to recognize non-coding variants as pathogenic. We here present a case where a collective body of evidence resulted in the identification and conclusive classification of a pathogenic deep intronic variant in <em>ATRX</em>. This report demonstrates the utility of a multi-platform approach in aiding the identification of pathogenic variants outside coding regions. Furthermore, it marks the first reported instance of a deep intronic pathogenic variant in <em>ATRX</em>.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"69 ","pages":"Article 104949"},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000417/pdfft?md5=ca2643e3174bf877c4c08c00b030059f&pid=1-s2.0-S1769721224000417-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid detection of common variants and deletions of CYP21A2 using MALDI-TOF MS","authors":"Xiaoshan Yin ,&nbsp;Yiming Lin ,&nbsp;Ting Zhang ,&nbsp;Haixia Miao ,&nbsp;Lingwei Hu ,&nbsp;Zhenzhen Hu ,&nbsp;Dou Zhou ,&nbsp;Benqing Wu ,&nbsp;Xinwen Huang","doi":"10.1016/j.ejmg.2024.104950","DOIUrl":"10.1016/j.ejmg.2024.104950","url":null,"abstract":"<div><p>Newborn screening (NBS) for congenital adrenal hyperplasia (CAH) based on hormonal testing is successfully implemented in many countries. However, this method cannot detect non-classic CAH and has high false positive rates. We have developed a novel MALDI-TOF MS assay that can identify common variants and deletions of <em>CYP21A2</em> in the Chinese population. Thirty-seven clinical patients with CAH confirmed by Sanger sequencing and MLPA analysis were detected by MALDI-TOF MS assay. Two <em>CYP21A2</em> variants were detected in 30 patients and one <em>CYP21A2</em> variant was detected in 7 patients. The MALDI-TOF MS assay detected 67 mutant alleles in 37 patients with a detection rate of 90.5%. Sanger sequencing revealed that three variants in seven patients were not included in the designed panel. Eleven distinct <em>CYP21A2</em> variants were identified, including five missense variants, two nonsense variants, two large gene deletions, one splice variant, and one frameshift variant. The most frequent variant was c.293-13C &gt; G (37.84%), followed by c.518T &gt; A (21.62%) and exon 1–7 deletion (17.57%).</p><p>The high-throughput MALDI-TOF MS assay that can simultaneously detect common variants and deletions of <em>CYP21A2</em>. This assay can be used for population-based genetic screening and rapid detection of suspected patients, and is expected to be a valuable complement to biochemical-based testing for the detection of CAH.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"69 ","pages":"Article 104950"},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000429/pdfft?md5=630a719a76933105527c0d68abf62e45&pid=1-s2.0-S1769721224000429-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atlantoaxial dislocation in the setting of NMLFS","authors":"Yousaf Abughofah ,&nbsp;Andrew J. Witten ,&nbsp;Ahmed Belal ,&nbsp;Saul Wilson","doi":"10.1016/j.ejmg.2024.104947","DOIUrl":"10.1016/j.ejmg.2024.104947","url":null,"abstract":"<div><h3>Background</h3><p>Nablus mask-like facial syndrome (NMFLS) is an extremely rare genetic syndrome characterized by facial dysmorphia as well as developmental delay. In the present report we describe a potential association between non-traumatic atlanto-occipital dislocation and NMFLS in an 11-year old female lacking typical facial features of NMFLS.</p></div><div><h3>Case description</h3><p>An 11-year-old female with autism presented with symptoms of persistent headache and vomiting as well as neck stiffness. Further investigation and CT imaging revealed congenital malformation of the skull base and craniocervical junction with complete posterior subluxation of the left occipital condyle. MRI findings later corroborated the findings on CT.</p></div><div><h3>Conclusions</h3><p>The patient was successfully treated with occipitocervical fusion. The findings in this case suggest the possibility that atlanto-occipital instability and generalized occipitocervical may be associated with NMFLS.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"69 ","pages":"Article 104947"},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000399/pdfft?md5=964ce72c27fa4eb1881b799cd19471d3&pid=1-s2.0-S1769721224000399-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital Adrenal Hyperplasia with Combined 21-hydroxylase deficiency and 17α-hydroxylase/17,20-lyase deficiency: An undervirilized male","authors":"Leyla Kara ,&nbsp;Dilek Cicek ,&nbsp;Ulku Gul Siraz ,&nbsp;Murat Erdogan ,&nbsp;Emre Sarikaya ,&nbsp;Ebru Gok ,&nbsp;Ugur Berber ,&nbsp;Selim Kurtoglu ,&nbsp;Mustafa Kendirci ,&nbsp;Nihal Hatipoglu","doi":"10.1016/j.ejmg.2024.104952","DOIUrl":"10.1016/j.ejmg.2024.104952","url":null,"abstract":"<div><p>21-hydroxylase deficiency stands as the most prevalent form of congenital adrenal hyperplasia, primarily resulting from mutations in the <em>CYP21A2</em> gene. On the other hand, mutations within the <em>CYP17A1</em> gene lead to 17α-hydroxylase/17,20-lyase enzyme deficiencies. The scarcity of 17-OH deficiency is noteworthy, accounting for less than 1% of all congenital adrenal hyperplasia cases. The male patient, born from a first-degree cousin marriage, exhibited several symptoms, including left undescended testis, micropenis, penile chord, left sensorineural hearing loss, and gynecomastia. He reported micropenis as a concern at the age of 13.5 years. His hormone profile revealed high levels of serum 17-hydroxyprogesterone, progesterone, and pregnenolone.</p><p>In this case with a 46 XY karyotype, suspicions arose regarding Cytochrome P450 oxidoreductase deficiency due to ambiguous genitalia and an atypical hormone profile. Analysis unveiled two distinct homozygous and pathogenic variants in the <em>CYP21A2</em> and <em>CYP17A1</em> genes. Notably, mineralocorticoid precursors escalated, while cortisol and sex steroid precursors decreased during the high (250 mcg) dose ACTH stimulation test. The mutation c.1169C &gt; G (p.Thr390Arg) in <em>CYP17A1</em>, which is the second documented case in literature, stands out due to its unique set of accompanying features.</p><p>Mutations occurring in <em>CYP21A2</em> and <em>CYP17A1</em> result in complete or partial enzyme deficiencies, and the detection of homozygous mutations in two different enzyme systems within the steroidogenic pathway is noteworthy.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"69 ","pages":"Article 104952"},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000442/pdfft?md5=06bf77af6c1ebc7f8f6262312306033c&pid=1-s2.0-S1769721224000442-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the clinical spectrum of Coffin-Siris syndrome with anorectal malformations: Case report and review of the literature","authors":"Ralah Alharbi ,&nbsp;Anna Suchet-Dechaud ,&nbsp;Inès Harzallah ,&nbsp;Renaud Touraine ,&nbsp;Francis Ramond","doi":"10.1016/j.ejmg.2024.104948","DOIUrl":"10.1016/j.ejmg.2024.104948","url":null,"abstract":"<div><p>Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly heterogeneous and still poorly understood. We report a 4-year-old girl who initially presented with an isolated ARM, and subsequently developed a global developmental delay as part of an <em>ARID1B</em>-related Coffin-Siris syndrome (CSS). A co-occurrence of ARMs and CSS in an individual by chance is unexpected since both diseases are very rare. A review of the literature enabled us to identify 10 other individuals with both CSS and ARMs. Among the ten individuals reported in this study, 8 had a variant in <em>ARID1A</em>, 2 in <em>ARID1B</em>, and 1 in <em>SMARCA4</em>. This more frequent than expected association between CSS and ARM indicates that some ARMs are most likely part of the CSS spectrum, especially for <em>ARID1A</em>-related CSS.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"69 ","pages":"Article 104948"},"PeriodicalIF":1.9,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000405/pdfft?md5=8fdae3655baf49ee13a375a2daa3d4bb&pid=1-s2.0-S1769721224000405-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal and neonatal phenotype of Larsen of La Réunion Island syndrome (B4GALT7-linkeropathy)","authors":"Jean-Luc Alessandri ,&nbsp;Tristan Celse ,&nbsp;Marta Spodenkiewicz ,&nbsp;Anais Calaya ,&nbsp;Coralie Dumont ,&nbsp;Marie-Line Jacquemont ,&nbsp;Bénédicte Bertaut-Nativel ,&nbsp;Brahim Boumahni ,&nbsp;Mathilde Rémy ,&nbsp;Fanny Ferroul ,&nbsp;Suzie Guilly ,&nbsp;Thomas Huby ,&nbsp;Mireille Irabé ,&nbsp;Tiffany Laurens ,&nbsp;Patrick Munier ,&nbsp;Godelieve Morel ,&nbsp;Frédérique Payet ,&nbsp;Hanitra Randrianaivo ,&nbsp;Bérénice Doray ,&nbsp;Jessica Dospeux","doi":"10.1016/j.ejmg.2024.104940","DOIUrl":"10.1016/j.ejmg.2024.104940","url":null,"abstract":"&lt;div&gt;&lt;p&gt;Larsen of La Réunion Island syndrome (LRS) is an autosomal recessive condition associated with multiple large joint dislocations, clubfeet, severe dwarfism, and distinctive facial features. LRS is caused by a recurrent homozygous variant in &lt;em&gt;B4GALT7&lt;/em&gt; gene with a founder effect in La Réunion population. Proteoglycans (PG) that are a major component of the extracellular matrix, are composed of a core protein connected to a glycosaminoglycans side chain via a tetrasaccharide linker region&lt;em&gt;. B4GALT7&lt;/em&gt; encodes galactosyltransferase I, one of the enzymes involved in the biosynthesis of the linker region. Conditions caused by pathogenic biallelic variants in genes implicated in the synthesis of the tetrasaccharide linker of PG are known as linkeropathies.&lt;/p&gt;&lt;p&gt;Prenatal features are rarely described in this group of chondrodysplasias. We present a series of 12 unpublished patients having LRS and describe the perinatal phenotype. All the patients had a prenatal growth restriction with brevity of limbs. The other features revealed by ultrasounds were increased nuchal translucency at 10–12 weeks of gestation (50 %), feet abnormalities (clubfeet or metatarsus varus) (25 %), dislocation affecting at least one large joint (elbow, knee, wrist) (25 %). Bilateral bowing of femora was noted for two fetuses. Fibular hypertrophy was noted for one fetus. Prenatal helical computed tomography (CT) performed in three pregnancies showed additional data such as bowing of the forearm bones, proximal radio-ulnar synostosis, or dislocation of large joints. Prenatal sonographic and helical CT findings led to the prenatal diagnosis of LRS in four patients. We confirm that the neonatal clinical picture of LRS has an important overlap with that reported in patients with B4GALT7 deficiency outside La Réunion Island and other linkeropathies. The core of the phenotypic spectrum combines low birth height, micromelia, hypermobility, dislocation of at least one large joint, facial features with prominent eyes, microstomia, depressed nasal bridge, and midface hypoplasia. Other clinical features include clubfeet (33%), bifid thumb in one patient, and cardiac abnormalities in two patients. Radiological findings include radio-ulnar synostosis (75%), metaphyseal flaring, precocious carpal ossification, and a Swedish key appearance of the proximal femora. Finally, we also report radiological features rarely described in B4GALT7-linkeropathies, including bowing of the femora and fibular hypertrophy. Our results confirm the phenotypic continuum of LRS within linkeropathies with some additional findings, including a high frequency of clubfeet usually described in B3GALT6-linkeropathies, the presence of congenital heart diseases usually described in B3GAT3-linkeropathies, and a high frequency of metaphyseal flaring usually reported in B3GALT6 or XITLT1-linkeropathies.&lt;/p&gt;&lt;p&gt;This is the first study that describes the perinatal phenotype in a cohort of patients with LRS. Thi","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"69 ","pages":"Article 104940"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000326/pdfft?md5=507e128f628c55f8f9741a4ef27e835f&pid=1-s2.0-S1769721224000326-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel splicing variant in MICAL-1 gene is associated with epilepsy","authors":"Haiyan Yang ,&nbsp;Hongmei Liao ,&nbsp;Siyi Gan ,&nbsp;Ting Xiao ,&nbsp;Liwen Wu","doi":"10.1016/j.ejmg.2024.104946","DOIUrl":"https://doi.org/10.1016/j.ejmg.2024.104946","url":null,"abstract":"<div><p>Germline <em>MICAL1</em> defects have been rarely reported in patients with epilepsy and the genotype-phenotype association remains unclear. In this study, the patient was a 4.6 years old girl who presented with onset of recurrent focal seizures with onset at age 3.4 years. EEG showed abnormal δ-wave activity in the right central and middle temporal lobe. Trio WES showed a novel heterozygous variant c.-43-1G &gt; A in the <em>MICAL1</em> gene in the patient and her normal mother. Minigene verified two abnormal transcripts due to the mutation, which was predicted to interrupt 5′UTR structures of MICAL1. The patient was clinically diagnosed with benign childhood epilepsy with centrotemporal spike (BECTS). As far as we know, this is the first BECTS case with documented <em>MICAL1</em> mutation<em>.</em> Novel <em>MICAL1</em> variant c.-43-1G &gt; A putatively interrupted MICAL1 translation by changing 5′UTR structures and, however, further functioning study is needed.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"69 ","pages":"Article 104946"},"PeriodicalIF":1.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000387/pdfft?md5=72b700457318ae4924367daf66984b90&pid=1-s2.0-S1769721224000387-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140843309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DPF2-related Coffin-Siris syndrome type 7 in two generations","authors":"Konstantinos Kolokotronis ,&nbsp;Aude-Annick Suter ,&nbsp;Ivan Ivanovski ,&nbsp;Tanja Frey ,&nbsp;Angela Bahr ,&nbsp;Anita Rauch ,&nbsp;Katharina Steindl","doi":"10.1016/j.ejmg.2024.104945","DOIUrl":"10.1016/j.ejmg.2024.104945","url":null,"abstract":"<div><p>To date 11 patients with Coffin-Siris syndrome type 7 (OMIM 618027) have been described since the first literature report. All reported patients carried de novo variants with presumed dominant negative effect, which localized in the PHD1/PHD2 domains of DPF2.</p><p>Here we report on the first familial case of Coffin-Siris syndrome type 7. The index patient presented during the 1st year of life with failure to thrive and ectodermal anomalies. The genetic analysis using whole exome sequencing showed a likely pathogenic missense variant in the PHD1 region. The family analysis showed that the mother as well as the older brother of the index patient also carried the detected <em>DPF2</em> variant in heterozygous state. The mother had a history of school difficulties but no history of failure to thrive and was overall mildly affected. The brother showed developmental delay with autistic features, ectodermal anomalies and overlapping morphologic features but did not have a history of growth failure problems.</p><p>To our knowledge this is the first report of an inherited likely pathogenic variant in <em>DPF2</em>, underlining the variability of the associated phenotype as well as the importance of considering inherited <em>DPF2</em> variants during the variant filtering strategy of whole exome data.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"69 ","pages":"Article 104945"},"PeriodicalIF":1.9,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000375/pdfft?md5=741d8e9bbb54f7f369c3815eb85ba06d&pid=1-s2.0-S1769721224000375-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}