European journal of medical genetics最新文献

{"title":"Analysis of UGT1A1 genotype-phenotype correlation in Chinese patients with gilbert and crigler-Najjar II syndrome","authors":"Lina Wu ,&nbsp;Zhenkun Li ,&nbsp;Yi Song ,&nbsp;Yanmeng Li ,&nbsp;Wei Zhang ,&nbsp;Xuemei Zhong ,&nbsp;Xiaoming Wang ,&nbsp;Jian Huang ,&nbsp;Xiaojuan Ou","doi":"10.1016/j.ejmg.2024.104962","DOIUrl":"10.1016/j.ejmg.2024.104962","url":null,"abstract":"<div><p>The spectrum of UDP-glucuronosyltransferase (<em>UGT1A1</em>) variants, which are associated with Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS-II), has been reported in Chinese and western countries. However, the genotype-phenotype correlation of the individual <em>UGT1A1</em> variants in GS and CNS-II remains to be clarified. To explore the <em>UGT1A1</em> variant pattern and genotype-phenotype correlations, we enrolled 310 Chinese patients, including 232 patients with GS and 78 with CNS-II. Peripheral blood samples were collected for screening variants in the gene <em>UGT1A1</em> by a polymerase chain reaction and Sanger sequencing. The correlation between different <em>UGT1A1</em> variants and clinical phenotypes was analyzed. A total of 21 <em>UGT1A1</em> variants were identified, including nine novel variants, and constituted 42 <em>UGT1A1</em> genotypes in the GS and CNS-II patients. The most common <em>UGT1A1</em> variants were A (TA)₇TAA, p.G71R, p.Y486D, p.P364L, and p.P229Q, which were different from western countries. The p.Y486D variant had higher minor allele frequency in CNS-II than in GS whereas the A (TA)₇TAA variant had higher minor allele frequency in GS than in CNS-II. The serum total bilirubin and triglyceride had significant differences among 14 recurrent genotypes of <em>UGT1A1</em>, in which the serum total bilirubin in patients with compound p.Y486D (homozygous)/p.G71R variant was significantly higher compared with homozygous A (TA)₇TAA, homozygous p.G71R, compound heterozygous A (TA)₇TAA/p.G71R and A (TA)₇TAA/p.P364L, and combined heterozygous A (TA)₇TAA/p.G71R/p.P229Q, while the serum triglyceride in patients with combined A (TA)₇TAA (homozygous)/p.P229Q variant was significantly higher compared with compound heterozygous A (TA)₇TAA/p.G71R, single heterozygous A (TA)₇TAA, single heterozygous p.G71R, and homozygous A (TA)₇TAA. The spectrum of <em>UGT1A1</em> genotypes in Chinese patients was distinct from western countries. There were differential levels of serum total bilirubin and triglyceride in patients with recurrent genotypes of <em>UGT1A1</em>.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104962"},"PeriodicalIF":1.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000545/pdfft?md5=9e77faf37264755b09f453e41e49702e&pid=1-s2.0-S1769721224000545-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787616","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":"Attitudes towards disclosure of familial genetic risk in a Mediterranean island population – A survey of the Maltese population","authors":"Dillon Mintoff ,&nbsp;Bettina Booker ,&nbsp;Shannon Debono ,&nbsp;Matthias Farrugia ,&nbsp;Nikolai Paul Pace","doi":"10.1016/j.ejmg.2024.104961","DOIUrl":"10.1016/j.ejmg.2024.104961","url":null,"abstract":"<div><p>Germline genetic testing has implications that extend beyond the individual patient to relatives, particularly for high-penetrance variants implicated in hereditary cancer or neurodegenerative syndromes. Many countries encourage patient-led communication to inform at-risk relatives, although the efficacy and uptake of this approach varies. Alternative scenarios envisage direct contact mediated by clinicians. The familial disclosure of sensitive genetic information is also determined by complex socio-ethnic factors. To date, no study has explored whether relatives would want to be informed of familial genetic risk and their preferences on different methods of communication in Malta. We thus used a published instrument that utilizes hypothetical scenario methodology to survey the attitudes of the Maltese population (n = 334) to receiving genetic information from family members. Two vignettes on Huntington's disease and colorectal cancer were presented. We also explored preferences towards the communication of genetic risk, confidentiality, and disclosure policies. Our preliminary results show that most respondents want to be informed of their increased risk by a family member or a clinician and would opt to receive confirmatory genetic testing. Most respondents preferred being informed of genetic risk by a close relative, but in the case of non-disclosure would want to be informed by a clinician. Most respondents expressed preference in favour of the introduction of registries, legislative change and sharing of contact details to address cases of nondisclosure. Our findings contribute further to evidence that supports, in selected hypothetical scenarios, an envisioned change in disclosure of genetic data policy by the public that is different from current practice to date.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"71 ","pages":"Article 104961"},"PeriodicalIF":1.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000533/pdfft?md5=32967b439a1a6a2379787c84851abf01&pid=1-s2.0-S1769721224000533-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757898","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":"Increased frequency of infections and autoimmune disease in adults with PTEN Hamartoma Tumour Syndrome","authors":"Meggie M.C.M. Drissen ,&nbsp;Janet R. Vos ,&nbsp;Estel Collado Camps ,&nbsp;Janneke H.M. Schuurs-Hoeijmakers ,&nbsp;Jolanda H. Schieving ,&nbsp;Nicoline Hoogerbrugge","doi":"10.1016/j.ejmg.2024.104960","DOIUrl":"10.1016/j.ejmg.2024.104960","url":null,"abstract":"<div><p>There are indications for immune dysregulation in <em>PTEN</em> Hamartoma Tumour Syndrome (PHTS), however information on the clinical immune phenotype is lacking. We aimed to assess the frequency of infections and autoimmune disease in PHTS patients. A retrospective cohort study including 81 paediatric and 109 adult PHTS patients and 73 female adult controls and self-reported data from yearly surveillance visits. Differences between adult patients and controls were assessed with odds ratios (OR). Of paediatric patients, 1% reported fungal infections, 23% tonsillectomy/adenoidectomy, 36% bacterial infections requiring antibiotics, and 2% autoimmune disease. Of adult patients, up to 67% repeatedly reported fungal infections, and 73% was ever affected which was similar to controls. Compared to controls, adult patients more often reported (signs of) viral infections: tonsillectomy/adenoidectomy (78%; OR = 7.4 (95%CI: 3.7–15.8)), frequent infections during childhood (43%; OR = 2.5 (95%CI: 1.3–5.2)), and flu or cold infections more often than others (49%; OR = 3.9 (95%CI: 2.0–8.0)). Autoimmune disease was also more frequent (24%, OR = 2.7 (95%CI: 1.1–7.3)) in adult patients, and antibiotics use (38%, OR = 4.7 (95%CI: 1.3–23.0)) in female adult patients. PHTS patients experience a broad clinical phenotype of immune dysregulation. At adult age, this consists of more often viral and bacterial infections and autoimmune disease, and repetitive fungal infections.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"70 ","pages":"Article 104960"},"PeriodicalIF":1.6,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000521/pdfft?md5=ef7365bbdd76407b8376aea727ac5047&pid=1-s2.0-S1769721224000521-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723309","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":"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}