European journal of medical genetics最新文献

{"title":"Fetal hepatic calcification in severe KAT6A (Arboleda-Tham) syndrome","authors":"Antonella Di Caprio, Cecilia Rossi, Emma Bertucci, Luca Bedetti, Natascia Bertoncelli, Francesca Miselli, Lucia Corso, Carolina Bondi, Lorenzo Iughetti, Alberto Berardi, Licia Lugli","doi":"10.1016/j.ejmg.2023.104906","DOIUrl":"https://doi.org/10.1016/j.ejmg.2023.104906","url":null,"abstract":"<p>Arboleda-Tham syndrome (ARTHS, MIM 616268) is a rare genetic disease, due to a pathogenic variant of Lysine (K) Acetyltransferase 6A (<em>KAT6A</em>) with autosomal dominant inheritance. Firstly described in 2015, ARTHS is one of the more common causes of undiagnosed syndromic intellectual disability. Due to extreme phenotypic variability, ARTHS clinical diagnosis is challenging, mostly at early stage of the disease. Moreover, because of the wide and unspecific spectrum of ARTHS, identification of the syndrome during prenatal life rarely occurs. Therefore, reported cases of <em>KAT6A</em> syndrome have been identified primarily through clinical or research exome sequencing in a gene-centric approach.</p><p>In order to expands the genotypic and phenotypic spectrum of ARTHS, we describe prenatal and postnatal findings in a patient with a novel frameshift <em>KAT6A</em> pathogenic variant, displaying a severe phenotype with previously unreported clinical features.</p>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"54 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139018312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathological mandibular fracture complicated by osteonecrosis in an adult patient with pycnodysostosis: Clinical report and review of the literature","authors":"Alice Moroni, Evelise Brizola, Alessia Di Cecco, Morena Tremosini, Marta Sergiampietri, Alberto Bianchi, Barbara Tappino, Maria Piana, Maria Gnoli","doi":"10.1016/j.ejmg.2023.104904","DOIUrl":"https://doi.org/10.1016/j.ejmg.2023.104904","url":null,"abstract":"<p>Pycnodysostosis is an ultra-rare osteosclerotic skeletal disorder characterized by short stature, susceptibly to fractures, acroosteolysis of the distal phalanges, and craniofacial features (frontal bossing, prominent nose, obtuse mandibular angle, micrognathia). Dental abnormalities (delayed eruption of teeth, hypodontia, malocclusion, dental crowding, persistence of deciduous teeth, enamel hypoplasia, and increased caries) are also frequent; due to bone metabolism alteration, the patients have an increased risk for jaw osteomyelitis, especially after tooth extraction or mandible fracture. Other complications are obstructive sleep apnea, endocrine alterations and cytopenia. Pycnodysostosis is caused by biallelic loss of function variants in <em>CTSK</em> gene, coding the lysosomal protease cathepsin K. CTSK is involved in the degradation of bone matrix proteins, such as type I and type II collagen. In pycnodysostosis, this degradation is decreased, leading to increased bone density and bone fragility with pathological fractures and poor healing.</p><p>We present a clinical report of a female adult patient with typical pycnodysostosis phenotype. At the age of 52 years, she had a pathological spontaneous fracture of the right mandible complicated by osteonecrosis, treated with load bearing osteosynthesis. The direct sequencing of <em>CTSK</em> gene revealed the presence of the pathogenic homozygous variant c.746 T &gt; A, (p.Ile249Asn), that confirmed the diagnosis of pycnodysostosis.</p><p>We also review the literature case series published to date, that suggest to always consider the diagnosis of pycnodysostosis in case of osteosclerosis, even in the absence of brachydactyly or short stature.</p><p>This report details the natural history of the disease in this patient, from childhood to adulthood, and highlights the importance of a quality of life assessment. In addition, we describe a case of mandibular osteonecrosis and spontaneous fracture in pycnodysostosis, drawing attention on the maxillofacial complications in these patients and on the importance of a personalized follow-up.</p>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"9 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139018016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal hepatic calcification in severe KAT6A (Arboleda-Tham) syndrome","authors":"Antonella Di Caprio ,&nbsp;Cecilia Rossi ,&nbsp;Emma Bertucci ,&nbsp;Luca Bedetti ,&nbsp;Natascia Bertoncelli ,&nbsp;Francesca Miselli ,&nbsp;Lucia Corso ,&nbsp;Carolina Bondi ,&nbsp;Lorenzo Iughetti ,&nbsp;Alberto Berardi ,&nbsp;Licia Lugli","doi":"10.1016/j.ejmg.2023.104906","DOIUrl":"10.1016/j.ejmg.2023.104906","url":null,"abstract":"<div><p>Arboleda-Tham syndrome (ARTHS, MIM 616268) is a rare genetic disease, due to a pathogenic variant of Lysine (K) Acetyltransferase 6A (<em>KAT6A</em>) with autosomal dominant inheritance. Firstly described in 2015, ARTHS is one of the more common causes of undiagnosed syndromic intellectual disability. Due to extreme phenotypic variability, ARTHS clinical diagnosis is challenging, mostly at early stage of the disease. Moreover, because of the wide and unspecific spectrum of ARTHS, identification of the syndrome during prenatal life rarely occurs. Therefore, reported cases of <em>KAT6A</em> syndrome have been identified primarily through clinical or research exome sequencing in a gene-centric approach.</p><p>In order to expands the genotypic and phenotypic spectrum of ARTHS, we describe prenatal and postnatal findings in a patient with a novel frameshift <em>KAT6A</em> pathogenic variant, displaying a severe phenotype with previously unreported clinical features.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104906"},"PeriodicalIF":1.9,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223002124/pdfft?md5=4e32d8a31f826a15255c7f3521c22167&pid=1-s2.0-S1769721223002124-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139015711","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":"Deep intronic variant causes aberrant splicing of ATP7A in a family with a variable occipital horn syndrome phenotype","authors":"J. Robert Harkness ,&nbsp;Huw B. Thomas ,&nbsp;Jill E. Urquhart ,&nbsp;Peter Jamieson ,&nbsp;Genomics England Research Consortium,&nbsp;Raymond T. O'Keefe ,&nbsp;Helen M. Kingston ,&nbsp;Charulata Deshpande ,&nbsp;William G. Newman","doi":"10.1016/j.ejmg.2023.104907","DOIUrl":"10.1016/j.ejmg.2023.104907","url":null,"abstract":"<div><p>Genetic variants in <em>ATP7A</em> are associated with a spectrum of X-linked disorders. In descending order of severity, these are Menkes disease, occipital horn syndrome, and X-linked distal spinal muscular atrophy. After 30 years of diagnostic investigation, we identified a deep intronic <em>ATP7A</em> variant in four males from a family affected to variable degrees by a predominantly skeletal phenotype, featuring bowing of long bones, elbow joints with restricted mobility which dislocate frequently, coarse curly hair, chronic diarrhoea, and motor coordination difficulties. Analysis of whole genome sequencing data from the Genomics England 100,000 Genomes Project following clinical re-evaluation identified a deep intronic <em>ATP7A</em> variant, which was predicted by SpliceAI to have a modest splicing effect. Using a mini-gene splicing assay, we determined that the intronic variant results in aberrant splicing. Sanger sequencing of patient cDNA revealed <em>ATP7A</em> transcripts with exon 5 skipping, or inclusion of a novel intron 4 pseudoexon. In both instances, frameshift leading to premature termination are predicted. Quantification of <em>ATP7A</em> mRNA transcripts using a qPCR assay indicated that the majority of transcripts (86.1 %) have non-canonical splicing, with 68.0 % featuring exon 5 skipping, and 18.1 % featuring the novel pseudoexon. We suggest that the variability of the phenotypes within the affected males results from the stochastic effects of splicing. This deep intronic variant, resulting in aberrant <em>ATP7A</em> splicing, expands the understanding of intronic variation on the <em>ATP7A</em>-related disease spectrum.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104907"},"PeriodicalIF":1.9,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223002136/pdfft?md5=bb3e0f88d3668032e706f2e7bc170915&pid=1-s2.0-S1769721223002136-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139017995","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":"Associated anomalies in anophthalmia and microphthalmia","authors":"Claude Stoll,&nbsp;Beatrice Dott,&nbsp;Yves Alembik,&nbsp;Marie-Paule Roth","doi":"10.1016/j.ejmg.2023.104892","DOIUrl":"10.1016/j.ejmg.2023.104892","url":null,"abstract":"<div><p>Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these associated anomalies vary between different studies. The purpose of this investigation was to assess the frequency and the types of associated anomalies among cases with an/microphthalmia in a geographically well defined population of northeastern France of 387,067 consecutive pregnancies from 1979 to 2007. Of the 98 infants with an/microphthalmia born during this period (prevalence at birth of 2.53 per 10,000), 88.8 % had associated anomalies. Cases with associated anomalies were divided into recognizable conditions (25 (25.5%) cases with chromosomal and 17 (17.3%) cases with non chromosomal conditions), and non recognizable conditions (45–45.9%- cases with multiple congenital anomalies –MCA). Trisomy 13 and trisomy 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, oculo-auriculo-vertebral spectrum, CHARGE syndrome and VACTERL association were most often present in recognizable non chromosomal conditions. Anomalies in the musculoskeletal, cardiovascular and central nervous systems were the most common other anomalies in cases with MCA and non recognizable conditions. However, given the limitation of the limited numbers of cases there should be urging caution in interpreting these results. In conclusion the frequency of associated anomalies in infants with anophthalmia and microphthalmia emphasizes the need for a thorough investigation of these cases. Routine screening for other anomalies especially musculoskeletal, cardiac and central nervous systems anomalies may need to be considered in infants with anophthalmia and microphthalmia, and referral of these cases for genetic counselling seems warranty.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104892"},"PeriodicalIF":1.9,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223001982/pdfft?md5=cbbb1e5ccfb2f35826c3ed31b9d6f4f4&pid=1-s2.0-S1769721223001982-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138679749","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":"LRP4 site-specific variants in the third β-propeller domain causes congenital myasthenic syndrome type 17","authors":"Tariq Al Jabry ,&nbsp;Nadia Al-Hashmi ,&nbsp;Basem Abdelhadi ,&nbsp;Almundher Al-Maawali","doi":"10.1016/j.ejmg.2023.104903","DOIUrl":"10.1016/j.ejmg.2023.104903","url":null,"abstract":"<div><p><em>LRP4</em> is expressed in many organs. It mediates SOST-dependent inhibition of bone formation and acts as an inhibitor of WNT signaling. It is also a postsynaptic end plate cell surface receptor at the neuromuscular junction and is central to its development, maintenance, and function. Pathogenic variants of <em>LRP4</em> that specifically affect the canonical WNT signaling pathway are known to be associated with Cenani-Lenz syndactyly syndrome or the overlapping condition sclerosteosis. However, site-specific pathogenic variants of <em>LRP4</em> have been associated with the congenital myasthenic syndrome (CMS) type 17 with no abnormal bone phenotype. Only two studies reported biallelic variants of <em>LRP4</em> associated with CMS17 that presented during childhood. All three reported variants (NM_002334.4: p.Glu1233Ala, p.Glu1233Lys, or p.Arg1277His) are located within the 3′-edge of the third β-propeller domain of LRP4. We report on a patient with a biallelic variant of the <em>LRP4</em> gene presenting with a severe and neonatal lethal phenotype; we also provide a literature review of the previously reported patients. A female neonate, born to healthy consanguineous parents, presented with severe hypotonia, congenital diaphragmatic hernia, pulmonary hypertension, and progressive hypoxemia. Two of her siblings presented with a similar condition in the past, and all three died shortly after birth. Clinical exome sequencing revealed homozygosity for the pathogenic variant NM_002334.4:c.3698A &gt; C (p.[Glu1233Ala]).</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104903"},"PeriodicalIF":1.9,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223002094/pdfft?md5=ed9c8eac37ac901f64ef05065e309c9a&pid=1-s2.0-S1769721223002094-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138632372","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":"GRM7-related disorder: five additional patients from three independent families and review of the literature","authors":"Louis Januel ,&nbsp;Nicolas Chatron ,&nbsp;Clotilde Rivier-Ringenbach ,&nbsp;Sara Cabet ,&nbsp;Audrey Labalme ,&nbsp;Yavuz Sahin ,&nbsp;Hossein Darvish ,&nbsp;Michael Kruer ,&nbsp;Somayeh Bakhtiari ,&nbsp;Damien Sanlaville ,&nbsp;Jean Madeleine de Sainte Agathe ,&nbsp;Gaetan Lesca","doi":"10.1016/j.ejmg.2023.104893","DOIUrl":"10.1016/j.ejmg.2023.104893","url":null,"abstract":"<div><p><span>Developmental and epileptic encephalopathies (DEEs) refer to a group of severe epileptic syndromes characterized by seizures as well as a developmental delay which can be a consequence of the underlying etiology and/or the epileptic encephalopathy. The genes responsible for DEEs are numerous and their number is increasing since the availability of Next-Generation Sequencing. Pathogenic variants in </span><em>GRM7</em><span>, encoding the metabotropic glutamate receptor 7<span><span>, were recently shown as a cause of a severe DEE with autosomal recessive inheritance<span>. To date, only ten patients have been reported in the literature, generally with severe phenotypes including early-onset epilepsy, microcephaly, </span></span>brain anomalies, and spasticity. We report here 5 patients from 3 independent families with biallelic variants in the </span></span><em>GRM7</em> gene. We review the literature and provide further elements for the understanding of the genotype-phenotype correlation of this rare syndrome.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104893"},"PeriodicalIF":1.9,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138566973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined achondroplasia and short stature homeobox-containing (SHOX) gene deletion in a Danish infant","authors":"Kasper V. Seiersen ,&nbsp;Tine B. Henriksen ,&nbsp;Ted C.K. Andelius ,&nbsp;Lotte Andreasen ,&nbsp;Tue Diemer ,&nbsp;Gudrun Gudmundsdottir ,&nbsp;Ida Vogel ,&nbsp;Vibike Gjørup ,&nbsp;Pernille A. Gregersen","doi":"10.1016/j.ejmg.2023.104894","DOIUrl":"10.1016/j.ejmg.2023.104894","url":null,"abstract":"<div><p>Short stature or shortening of the limbs can be the result of a variety of genetic variants. Achondroplasia is the most common cause of disproportionate short stature and is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene <em>(FGFR3)</em>.</p><p>Short stature homeobox (SHOX) deficiency is caused by loss or defects of the <em>SHOX</em> gene or its enhancer region. It is associated with a spectrum of phenotypes ranging from normal stature to Léri-Weill dyschondrosteosis characterized by mesomelia and short stature or the more severe Langer mesomelic dysplasia in case of biallelic SHOX deficiency.</p><p>Little is known about the interactions and phenotypic consequences of achondroplasia in combination with SHOX deficiency, as the literature on this subject is scarce, and no genetically confirmed clinical reports exist. We present the clinical findings in an infant girl with concurrent achondroplasia and SHOX deficiency. We conclude that the clinical findings in infancy are phenotypically compatible with achondroplasia, with no features of the SHOX deficiency evident. This may change over time, as some features of SHOX deficiency only become evident later in life.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104894"},"PeriodicalIF":1.9,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721223002008/pdfft?md5=a4c39365537104cc37b290b8715b8271&pid=1-s2.0-S1769721223002008-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138567376","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":"Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature","authors":"Yuri Sonoda ,&nbsp;Atsushi Fujita ,&nbsp;Michiko Torio ,&nbsp;Takahiko Mukaino ,&nbsp;Ayumi Sakata ,&nbsp;Masaru Matsukura ,&nbsp;Kousuke Yonemoto ,&nbsp;Ken Hatae ,&nbsp;Yuko Ichimiya ,&nbsp;Pin Fee Chong ,&nbsp;Masayuki Ochiai ,&nbsp;Yoshinao Wada ,&nbsp;Machiko Kadoya ,&nbsp;Nobuhiko Okamoto ,&nbsp;Yoshiko Murakami ,&nbsp;Tadashi Suzuki ,&nbsp;Noriko Isobe ,&nbsp;Hiroshi Shigeto ,&nbsp;Naomichi Matsumoto ,&nbsp;Yasunari Sakai ,&nbsp;Shouichi Ohga","doi":"10.1016/j.ejmg.2023.104895","DOIUrl":"10.1016/j.ejmg.2023.104895","url":null,"abstract":"<div><h3>Introduction</h3><p><em>NGLY1</em>-associated congenital disorder of deglycosylation (CDDG1: OMIM #<span>615273</span><svg><path></path></svg>) is a rare autosomal recessive disorder caused by a functional impairment of endoplasmic reticulum in degradation of glycoproteins. Neurocognitive dysfunctions have been documented in patients with CDDG1; however, deteriorating phenotypes of affected individuals remain elusive.</p></div><div><h3>Case presentation</h3><p>A Japanese boy with delayed psychomotor development showed ataxic movements from age 5 years and myoclonic seizures from age 12 years. Appetite loss, motor and cognitive decline became evident at age 12 years. Electrophysiological studies identified paroxysmal discharges on myoclonic seizure and a giant somatosensory evoked potential. Perampanel was effective for controlling myoclonic seizures. Exome sequencing revealed that the patient carried compound heterozygous variants in <em>NGLY1</em>, NM_018297.4: c.857G &gt; A and c.-17_12del, which were inherited from mother and father, respectively. A literature review confirmed that myoclonic seizures were observed in 28.5% of patients with epilepsy. No other patients had progressive myoclonic epilepsy or cognitive decline in association with loss-of-function variations in <em>NGLY1</em>.</p></div><div><h3>Conclusion</h3><p>Our data provides evidence that a group of patients with CDDG1 manifest slowly progressive myoclonic epilepsy and cognitive decline during the long-term clinical course.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"67 ","pages":"Article 104895"},"PeriodicalIF":1.9,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S176972122300201X/pdfft?md5=9d7033767721808e72668aad00d5b99e&pid=1-s2.0-S176972122300201X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138566972","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":"Clinical and molecular features of four families with CLDN10-related HELIX syndrome","authors":"Ahmad Qudair ,&nbsp;Maged Hussein ,&nbsp;Mohammed Alowain ,&nbsp;Zuhair Nasser Al-Hassnan ,&nbsp;Abdullah Alfaifi ,&nbsp;Abdullah Alfalah ,&nbsp;Mashael Al-Qahtani ,&nbsp;Fowzan S. Alkuraya","doi":"10.1016/j.ejmg.2023.104886","DOIUrl":"10.1016/j.ejmg.2023.104886","url":null,"abstract":"<div><p>Biallelic pathogenic variants in <em>CLDN10</em> cause the very rare and distinct <span>multiplex epithelium dysfunction manifested by hypohidrosis<span> and electrolyte imbalance (HELIX) syndrome</span></span><span><span>. HELIX patients often present with heat intolerance and reduced </span>tear secretion. Here, we report on eight new patients (four families) </span><span>who presented soon after birth with fine scales in the palms and soles and hypohidrosis that was associated with high body temperature.</span><span> Exome sequencing identified a novel homozygous pathogenic variant in </span><em>CLDN10</em><span> in one family (NM_006984:exon1:c.138G&gt;A:p.W46*) and a previously reported pathogenic founder variant in the other three (NM_006984:exon5:c.653del:P218Lfs*21). The detailed clinical reports of these patients and a review of previously reported patients further delineate the phenotype of this extremely rare disorder.</span></p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"66 12","pages":"Article 104886"},"PeriodicalIF":1.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}