European journal of medical genetics最新文献

{"title":"Cancer in 22q11.2 deletion syndrome: A case report and literature review","authors":"Bingju Liu,&nbsp;Yunfeng Lu,&nbsp;Qi Wang,&nbsp;Yunpeng Dai,&nbsp;Liying Liu","doi":"10.1016/j.ejmg.2024.104959","DOIUrl":"10.1016/j.ejmg.2024.104959","url":null,"abstract":"<div><p>Clinically, the 22q11.2 deletion syndrome (22q11.2DS) is considered the most commonly detected microdeletion syndrome. Hepatoblastoma is the most prevalent malignant liver cancer in childhood. However, cases of hepatoblastoma in children with 22q11.2DS have only been reported in four patients. In this report, we present a-13-year-old male treated at our center due to growth retardation, and later diagnosed with hepatoblastoma. Whole genome sequencing (WGS) identified 22q11.2DS. Chromosomal microarray analysis (CMA) of peripheral blood sample showed a 2.9 Mb deletion of chromosome 22q11.2. While underlying mechanisms remain unclear, our literature review suggests that patients with 22q11.2DS may show an elevated risk of malignancy. After reviewing 21 previously reported cases, we identified 33 individuals with both cancer and 22q11.2 DS or DiGeorge syndrome. Of these cases, 7 out of 33 (21%) were hematologic tumors, while 26 out of 33 (78%) were solid tumors.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104959"},"PeriodicalIF":1.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S176972122400051X/pdfft?md5=f1fb3f662d0aaf05a591060f90c4b32c&pid=1-s2.0-S176972122400051X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537733","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":"Safety and efficacy of burosumab in improving phosphate metabolism, bone health, and quality of life in adolescents with X-linked hypophosphatemic rickets","authors":"Giampiero I. Baroncelli ,&nbsp;Anna Grandone ,&nbsp;Antonio Aversa ,&nbsp;Maria Rita Sessa ,&nbsp;Caterina Pelosini ,&nbsp;Angela Michelucci ,&nbsp;Benedetta Toschi ,&nbsp;Mario Manca ,&nbsp;Alessandro Isola ,&nbsp;Pasquale Comberiati","doi":"10.1016/j.ejmg.2024.104958","DOIUrl":"10.1016/j.ejmg.2024.104958","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and objective&lt;/h3&gt;&lt;p&gt;X-linked hypophosphatemic rickets (XLH) is due to loss-of-function mutations in the phosphate-regulating endopeptidase homologue on the X chromosome (&lt;em&gt;PHEX&lt;/em&gt;) that lead to increased fibroblast growth factor 23 (FGF23) production. FGF23 excess causes renal phosphate wasting and insufficient 1,25-dihydroxyvitamin D (1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D) synthesis with reduced intestinal phosphate absorption, ultimately resulting in chronic hypophosphatemia.&lt;/p&gt;&lt;p&gt;Children with XLH show typical skeletal lesions of rickets, deformities of the lower limbs, stunted growth with disproportionate short stature, bone pain, and physical dysfunctions.&lt;/p&gt;&lt;p&gt;Burosumab, a fully human IgG1 monoclonal antibody that binds to FGF23 to inhibit its activity, is more effective to improve the biochemical and clinical signs of XLH than conventional treatment with phosphate supplements and vitamin D active metabolites. Data on adolescents with XLH during the transition period to young adulthood are few.&lt;/p&gt;&lt;p&gt;In this prospective case series, we aimed to assess safety and efficacy of burosumab in adolescents with XLH who discontinued long-term conventional therapy.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Five Caucasian adolescents (4 males, 1 female; mean age 15.4 ± 1.5 years) with XLH were recruited and switched from conventional treatment to burosumab (0.8–1.2 mg/kg, s. c. QW2). Burosumab was continued for 12–48 months and, once discontinued, patients were followed-up for 6–12 months. In all patients, serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D levels, and renal tubular reabsorption of phosphate (TmP/GFR) values were assessed at entry and during burosumab. Intact FGF23 plasma levels were measured at entry. Patient-reported outcomes (PROs) were assessed at entry and every 3–6 months to evaluate the impact of low extremity pain, stiffness, and difficulties performing daily activities.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;At entry, all patients showed hypophosphatemia, increased intact FGF23 levels, reduced TmP/GFR, insufficient 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D levels, and in four out of five increased ALP levels. Two patients had radiological signs of rickets. During burosumab, all patients showed a significant increase in serum phosphate and 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D levels, and in TmP/GFR values (P &lt; 0.05 - P &lt; 0.0001). Serum ALP levels significantly declined (P &lt; 0.05) to normal values. No changes of serum calcium and PTH levels (P&lt;img&gt;NS) were found during burosumab. PROs significantly improved (P &lt; 0.02 - P &lt; 0.0001) in all patients. Four patients discontinued burosumab when they turned 18 or 19, whereas one continued the treatment since he was still younger than 18 during the study period. Four patients who suspended burosumab showed a rapid decline in serum phosphate and 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D levels and in TmP/GFR values; serum ALP levels increased, and PROs progressively worsened ","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104958"},"PeriodicalIF":1.6,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000508/pdfft?md5=1af36568f8c0c52967aa10a0676d7f49&pid=1-s2.0-S1769721224000508-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476240","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":"The discovery of a ten-generation m.C1494T pedigree in the east of England with probable links to King Richard III","authors":"Ian S. Logan","doi":"10.1016/j.ejmg.2024.104957","DOIUrl":"10.1016/j.ejmg.2024.104957","url":null,"abstract":"<div><p>This paper reports the discovery of a m.C1494T pedigree in the east of England made during a search for matrilineal relations of King Richard III.</p><p>The mitochondrial DNA variant m.C1494T has been associated with aminoglycoside-induced deafness. This variant is very uncommon. although pedigrees with this variant have previously been found in China and Spain. The members of the newly identified pedigree all belong to the mitochondrial haplogroup J1c2c3, which is also the haplogroup of King Richard III. The presence of a few people in the USA from the same haplogroup has previously been noted, and it is now known that one of the people can show his descent from a couple who lived in Nottinghamshire, England, in the late 1700's. The mitochondrial DNA sequence of this man, at present living in the USA, and of his 4th cousin, twice removed, living in Lincoln, England, has shown they belong to haplogroup J1c2c3 and both have the variant m.C1494T; thereby, allowing the production of a multi-generational pedigree originating in the east of England. Fortunately, deafness has not been found in any living member of this large pedigree. It was also noted that the link to the family of King Richard III has not been firmly defined; however the circumstantial evidence is strong as many of his family members lived in this part of England.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104957"},"PeriodicalIF":1.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000491/pdfft?md5=d93f4e18c74f7ddec74cc1a587644e9f&pid=1-s2.0-S1769721224000491-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426528","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":"Retinoblastoma caused by an RB1 variant with unusually low penetrance in a Danish family","authors":"Pernille A. Gregersen ,&nbsp;Peter S. Jensen ,&nbsp;Rikke Christensen ,&nbsp;Dietmar Lohmann ,&nbsp;Hilary Racher ,&nbsp;Brenda Gallie ,&nbsp;Steen F. Urbak","doi":"10.1016/j.ejmg.2024.104956","DOIUrl":"10.1016/j.ejmg.2024.104956","url":null,"abstract":"<div><p>Retinoblastoma is the most common eye cancer in children. It is caused by pathogenic alterations of both alleles of the tumor suppressor gene <em>RB1</em>. In heritable retinoblastoma, a constitutional <em>RB1</em> variant predisposes the cells to tumor formation, and loss of the other allele is a prerequisite for the development of retinoblastoma.</p><p>Heritable retinoblastoma is inherited in an autosomal dominant manner; however, the majority of cases are the result of a <em>de novo</em> pathogenic <em>RB1</em> variant. Penetrance is usually high (&gt;90%), but with marked inter-familial variability. In some families, penetrance is incomplete and family members who develop tumors tend to remain unilaterally affected. Moreover, some families with low penetrance also show a parent-of-origin effect.</p><p>We describe a patient with unilateral retinoblastoma caused by a previously unreported likely pathogenic <em>RB1</em> variant (c.1199T&gt;C) that disrupts a highly conserved amino acid residue within the A-box functional domain. Segregation analysis showed that the variant had unusually low penetrance as nine non-affected family members carried the same variant. We emphasize the use of genetic analysis on tumor DNA for classifying the <em>RB1</em> variant, and underline the challenges in clinical management and counseling of families carrying the specific <em>RB1</em> variant.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104956"},"PeriodicalIF":1.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S176972122400048X/pdfft?md5=ee5ee02bf1d74ef6ed7603030f0dcab2&pid=1-s2.0-S176972122400048X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426527","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":"Biallelic loss-of-function variants in the centriolar protein CCP110 leads to a ciliopathy-like phenotype(s)","authors":"Hisato Suzuki ,&nbsp;Yukako Muramatsu ,&nbsp;Fuyuki Miya ,&nbsp;Hideyuki Asada ,&nbsp;Mamiko Yamada ,&nbsp;Gen Nishimura ,&nbsp;Kenjiro Kosaki ,&nbsp;Toshiki Takenouchi","doi":"10.1016/j.ejmg.2024.104955","DOIUrl":"10.1016/j.ejmg.2024.104955","url":null,"abstract":"<div><p>CCP110 (centriolar coiled coil protein 110, also known as CP110) is one of the essential proteins localized in the centrosome that plays critical roles in the regulation of the cell cycle and also in the initiation of ciliogenesis. So far, no human congenital disorders have been identified to be associated with pathogenic variants of <em>CCP110</em>. Mice with biallelic loss-of-function variants of <em>Ccp110</em> (<em>Ccp110</em>^−/−) are known to manifest multiple organ defects, including a small body size, polydactyly, omphalocele, congenital heart defects, cleft palate, short ribs, and a small thoracic cage, a pattern of abnormalities closely resembling that in \"ciliopathies\" in humans. Herein, we report a 7-month-old male infant who presented with growth failure and skeletal abnormalities, including a narrow thorax and severe brachydactyly. Trio exome analysis of the genomic DNA of the patient and his parents showed that the patient was a compound heterozygote for truncating variants of <em>CCP110</em>, including a frameshift variant NM_001323572.2:c.856_857del, p.(Val286Leufs*5) inherited from the father, and a nonsense variant NM_001323572.2:c.1129C&gt;T, p.(Arg377*) inherited from the mother. The strikingly similar pattern of malformations between <em>Ccp110</em>^−/− mice and the 7-month-old male infant reported herein carrying unequivocal truncating <em>CCP110</em> variants strongly supports the contention that <em>CCP110</em> is a novel disease-causative gene.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104955"},"PeriodicalIF":1.9,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000478/pdfft?md5=14326a0b8240aea844764b252f949238&pid=1-s2.0-S1769721224000478-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300323","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":"Natural history of acid sphingomyelinase deficiency among European patients during childhood and adolescence: A retrospective observational study","authors":"Eugen Mengel ,&nbsp;Maurizio Scarpa ,&nbsp;Nathalie Guffon ,&nbsp;Simon A. Jones ,&nbsp;Vishal Goriya ,&nbsp;Jérôme Msihid ,&nbsp;Valerie Dyevre ,&nbsp;Carly Rodriguez ,&nbsp;Maja Gasparic ,&nbsp;Lubomyra Nalysnyk ,&nbsp;Fernando Laredo ,&nbsp;Ruth Pulikottil-Jacob","doi":"10.1016/j.ejmg.2024.104954","DOIUrl":"10.1016/j.ejmg.2024.104954","url":null,"abstract":"<div><p>Acid sphingomyelinase deficiency (ASMD) is a rare, lysosomal storage disease with limited evidence on its natural history. This retrospective, medical record abstraction study aimed to characterize the natural history of ASMD (types B and A/B) during childhood and adolescence. Recruiting sites were European centers (i.e., France, Germany, Italy, and the United Kingdom) from the ASCEND-Peds trial (NCT02292654); these sites were targeted because of the rarity of ASMD and specialized care provided at these centers. The study population comprised ASMD trial patients (before exposure to treatment) and ASMD non-trial participants who were managed at the same trial sites. Overall, 18 patients were included (11 trials; 7 non-trials; median [Q1; Q3] age at ASMD diagnosis: 2.5 [1.0; 4.0] years). Median follow-up duration was 10.0 years. Frequently reported medical conditions were hepatobiliary (17 [94.4%]) and blood and lymphatic system disorders (16 [88.9%]). Adenoidectomy (3 [16.7%]) was the most commonly reported surgical procedures; gastroenteritis (5 [27.8%]) was the most frequently reported infections, and epistaxis (6 [33.3%]) was the most commonly reported bleeding events. Abnormal spleen (16 [88.9%]) and liver (15 [83.3%]) size and respiratory function (8 [44.4%]) were commonly reported during physical examination. Overall, 11 (61.1%) patients were hospitalized; 6 (33.3%) patients had emergency room visits. Findings were consistent with published literature and support the current understanding of natural history of ASMD.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104954"},"PeriodicalIF":1.9,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000466/pdfft?md5=9739bc009db2c62340a22cc7aa7f8c3e&pid=1-s2.0-S1769721224000466-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295801","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":"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}