European journal of medical genetics最新文献_第7页

The discovery of a ten-generation m.C1494T pedigree in the east of England with probable links to King Richard III 在英格兰东部发现了一个可能与理查德三世国王有关的 10 代 m.C1494T血统。

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2024-06-17 DOI: 10.1016/j.ejmg.2024.104957

Ian S. Logan

{"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}

引用次数: 0

Retinoblastoma caused by an RB1 variant with unusually low penetrance in a Danish family 在一个丹麦家族中，RB1变体引起的视网膜母细胞瘤具有异常低的渗透性。

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2024-06-17 DOI: 10.1016/j.ejmg.2024.104956

Pernille A. Gregersen , Peter S. Jensen , Rikke Christensen , Dietmar Lohmann , Hilary Racher , Brenda Gallie , Steen F. Urbak

{"title":"Retinoblastoma caused by an RB1 variant with unusually low penetrance in a Danish family","authors":"Pernille A. Gregersen , Peter S. Jensen , Rikke Christensen , Dietmar Lohmann , Hilary Racher , Brenda Gallie , 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 (>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>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}

引用次数: 0

Biallelic loss-of-function variants in the centriolar protein CCP110 leads to a ciliopathy-like phenotype(s) 中心极蛋白 CCP110 的双叶功能缺失变体会导致纤毛症样表型。

IF 1.9 4区医学

European journal of medical genetics Pub Date : 2024-06-08 DOI: 10.1016/j.ejmg.2024.104955

Hisato Suzuki , Yukako Muramatsu , Fuyuki Miya , Hideyuki Asada , Mamiko Yamada , Gen Nishimura , Kenjiro Kosaki , Toshiki Takenouchi

{"title":"Biallelic loss-of-function variants in the centriolar protein CCP110 leads to a ciliopathy-like phenotype(s)","authors":"Hisato Suzuki , Yukako Muramatsu , Fuyuki Miya , Hideyuki Asada , Mamiko Yamada , Gen Nishimura , Kenjiro Kosaki , 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><sup>−/−</sup>) 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>T, p.(Arg377*) inherited from the mother. The strikingly similar pattern of malformations between <em>Ccp110</em><sup>−/−</sup> 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}

引用次数: 0

Natural history of acid sphingomyelinase deficiency among European patients during childhood and adolescence: A retrospective observational study 欧洲儿童和青少年酸性鞘磷脂酶缺乏症的自然病史：一项回顾性观察研究。

IF 1.9 4区医学

European journal of medical genetics Pub Date : 2024-06-08 DOI: 10.1016/j.ejmg.2024.104954

Eugen Mengel , Maurizio Scarpa , Nathalie Guffon , Simon A. Jones , Vishal Goriya , Jérôme Msihid , Valerie Dyevre , Carly Rodriguez , Maja Gasparic , Lubomyra Nalysnyk , Fernando Laredo , Ruth Pulikottil-Jacob

{"title":"Natural history of acid sphingomyelinase deficiency among European patients during childhood and adolescence: A retrospective observational study","authors":"Eugen Mengel , Maurizio Scarpa , Nathalie Guffon , Simon A. Jones , Vishal Goriya , Jérôme Msihid , Valerie Dyevre , Carly Rodriguez , Maja Gasparic , Lubomyra Nalysnyk , Fernando Laredo , 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}

引用次数: 0

Jaberi-Elahi syndrome: Exploring a novel GTPBP2 mutation and a literature review 贾贝里-伊拉希综合征：探索一种新型 GTPBP2 基因突变及文献综述

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2024-06-07 DOI: 10.1016/j.ejmg.2024.104953

Jamal Manoochehri , Amirmasoud Shiri , Somayeh Khoddam , Maryam Aghasipour , Neda Kamal , Hossein Jafari Khamirani , Seyed Alireza Dastgheib , Mehdi Dianatpour , Seyed Mohammad Bagher Tabei

{"title":"Jaberi-Elahi syndrome: Exploring a novel GTPBP2 mutation and a literature review","authors":"Jamal Manoochehri , Amirmasoud Shiri , Somayeh Khoddam , Maryam Aghasipour , Neda Kamal , Hossein Jafari Khamirani , Seyed Alireza Dastgheib , Mehdi Dianatpour , 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 > 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}

引用次数: 0

Addressing diagnostic gaps and priorities of the global rare diseases community: Recommendations from the IRDiRC diagnostics scientific committee 解决全球罕见病群体的诊断差距和优先事项：IRDiRC 诊断科学委员会的建议。

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2024-06-06 DOI: 10.1016/j.ejmg.2024.104951

David R. Adams , Clara D.M. van Karnebeek , Sergi Beltran Agulló , Víctor Faùndes , Saumya Shekhar Jamuar , Sally Ann Lynch , Guillem Pintos-Morell , Ratna Dua Puri , Ruty Shai , Charles A. Steward , Biruté Tumiene , Alain Verloes , members of the IRDiRC Diagnostic Scientific Committee

{"title":"Addressing diagnostic gaps and priorities of the global rare diseases community: Recommendations from the IRDiRC diagnostics scientific committee","authors":"David R. Adams , Clara D.M. van Karnebeek , Sergi Beltran Agulló , Víctor Faùndes , Saumya Shekhar Jamuar , Sally Ann Lynch , Guillem Pintos-Morell , Ratna Dua Puri , Ruty Shai , Charles A. Steward , Biruté Tumiene , Alain Verloes , 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}

引用次数: 0

Identification of a pathogenic deep intronic variant in ATRX ends a diagnostic odyssey ATRX 深内含变体的致病性鉴定结束了诊断奥德赛。

IF 1.9 4区医学

European journal of medical genetics Pub Date : 2024-06-01 DOI: 10.1016/j.ejmg.2024.104949

Jasper J. van der Smagt , Angeliki P. Lampri , Iris de Lange , Mariëlle Alders , Michiel L. Houben , Marco J. Koudijs , Richard H. van Jaarsveld

引用次数: 0

Rapid detection of common variants and deletions of CYP21A2 using MALDI-TOF MS 利用 MALDI-TOF MS 快速检测 CYP21A2 的常见变体和缺失。

IF 1.9 4区医学

European journal of medical genetics Pub Date : 2024-06-01 DOI: 10.1016/j.ejmg.2024.104950

Xiaoshan Yin , Yiming Lin , Ting Zhang , Haixia Miao , Lingwei Hu , Zhenzhen Hu , Dou Zhou , Benqing Wu , Xinwen Huang

{"title":"Rapid detection of common variants and deletions of CYP21A2 using MALDI-TOF MS","authors":"Xiaoshan Yin , Yiming Lin , Ting Zhang , Haixia Miao , Lingwei Hu , Zhenzhen Hu , Dou Zhou , Benqing Wu , 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 > G (37.84%), followed by c.518T > 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}

引用次数: 0

Atlantoaxial dislocation in the setting of NMLFS 寰椎脱位与 NMLFS。

IF 1.9 4区医学

European journal of medical genetics Pub Date : 2024-06-01 DOI: 10.1016/j.ejmg.2024.104947

Yousaf Abughofah , Andrew J. Witten , Ahmed Belal , Saul Wilson

{"title":"Atlantoaxial dislocation in the setting of NMLFS","authors":"Yousaf Abughofah , Andrew J. Witten , Ahmed Belal , 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}

引用次数: 0

Congenital Adrenal Hyperplasia with Combined 21-hydroxylase deficiency and 17α-hydroxylase/17,20-lyase deficiency: An undervirilized male 21-羟化酶缺乏症和17α-羟化酶/17,20-赖氨酸酶缺乏症并发症：一名未完全恢复的男性。

IF 1.9 4区医学

European journal of medical genetics Pub Date : 2024-06-01 DOI: 10.1016/j.ejmg.2024.104952

Leyla Kara , Dilek Cicek , Ulku Gul Siraz , Murat Erdogan , Emre Sarikaya , Ebru Gok , Ugur Berber , Selim Kurtoglu , Mustafa Kendirci , Nihal Hatipoglu

{"title":"Congenital Adrenal Hyperplasia with Combined 21-hydroxylase deficiency and 17α-hydroxylase/17,20-lyase deficiency: An undervirilized male","authors":"Leyla Kara , Dilek Cicek , Ulku Gul Siraz , Murat Erdogan , Emre Sarikaya , Ebru Gok , Ugur Berber , Selim Kurtoglu , Mustafa Kendirci , 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 > 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}

引用次数: 0