• MeSH
• Agammaglobulinemia immunology   MeSH
• X Chromosome immunology   pathology   MeSH
• Granulomatous Disease, Chronic immunology   MeSH
• Immunoglobulins MeSH
• Chromosome Mapping methods   MeSH
• Immunologic Deficiency Syndromes diagnosis   genetics   MeSH
• Wiskott-Aldrich Syndrome immunology   MeSH
• Publication type
• Review MeSH

The green anole, Anolis carolinensis (ACA), is the model reptile for a vast array of biological disciplines. It was the first nonavian reptile to have its genome fully sequenced. During the genome project, the XX/XY system of sex chromosomes homologous to chicken chromosome 15 (GGA15) was revealed, and 106 X-linked genes were identified. We selected 38 genes located on eight scaffolds in ACA and having orthologs located on GGA15, then tested their linkage to ACA X chromosome by using comparative quantitative fluorescent real-time polymerase chain reaction applied to male and female genomic DNA. All tested genes appeared to be X-specific and not present on the Y chromosome. Assuming that all genes located on these scaffolds should be localized to the ACA X chromosome, we more than doubled the number of known X-linked genes in ACA, from 106 to 250. While demonstrating that the gene content of chromosome X in ACA and GGA15 is largely conserved, we nevertheless showed that numerous interchromosomal rearrangements had occurred since the splitting of the chicken and anole evolutionary lineages. The presence of many ACA X-specific genes localized to distinct contigs indicates that the ACA Y chromosome should be highly degenerated, having lost a large amount of its original gene content during evolution. The identification of novel genes linked to the X chromosome and absent on the Y chromosome in the model lizard species contributes to ongoing research as to the evolution of sex determination in reptiles and provides important information for future comparative and functional genomics.

• MeSH
• Genetic Linkage MeSH
• Gene Dosage MeSH
• Genes, X-Linked * MeSH
• Lizards genetics   MeSH
• Conserved Sequence MeSH
• Sex Factors MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Genetic Diseases, Inborn MeSH
• Infant MeSH
• Humans MeSH
• Lymphatic Diseases MeSH
• Immunologic Deficiency Syndromes MeSH
• Herpesvirus 4, Human MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

Kazuistika popisuje případ úspěšné prenatální diagnózy skeletální dysplazie v prvním trimestru gravidityu plodu ženy, postižené X-vázanou dominantní chondrodysplasia punctata (CDPX2). První těhotenství probandky bylo ukončeno vzhledem k postižení skeletu plodu ve druhém trimestru. V následujícím těhotenství byla diagnóza X-vázané dominantní chondrodysplasia punctata uzavřena v prvním trimestru gravidity –v 13. gestačním týdnu. Diagnostický závěr byl stanoven na podkladě ultrazvukového (UZ) vyšetření a DNA analýzy mutace v genu EBP v materiálu získaném biopsií choriových klků (CVS). KLÍČOVÁ SLOVA: prenatální diagnostika, ultrazvuk, X-vázaná dominantní chondrodysplasia punctata, DNA molekulární diagnostika

Case report describes successful prenatal diagnosis of skeletal dysplasia in the first trimester of pregnancy in a female patient affected with X-linked dominat chondrodysplasia punctata (CDPX2). Her first pregnancy was terminated in the second trimester due to skeletal dysplasia of the foetus. The diagnosis in the following pregnancy was finished in the first trimester – before the end of the 13th gestational week. The diagnosis was established on the basis of ultrasonographic (US) examination and mutation analysis of the EBP gene in the material of chorionic villus sampling (CVS). Keywords: prenatal diagnosis, ultrasonograpy, X-linked dominant chondrodysplasia punctata, DNA analysis

• Keywords
• DNA molekulární diagnostika,
• MeSH
• Chondrodysplasia Punctata * diagnosis   ultrasonography   MeSH
• Molecular Diagnostic Techniques MeSH
• Adult MeSH
• Genetic Techniques MeSH
• Genes, X-Linked MeSH
• Abortion, Induced MeSH
• Pregnancy Complications MeSH
• Humans MeSH
• Mutation genetics   MeSH
• Fetal Diseases ultrasonography   MeSH
• Chorionic Villi Sampling * MeSH
• Prenatal Diagnosis methods   MeSH
• Pregnancy Trimester, First MeSH
• Sequence Analysis, DNA MeSH
• Ultrasonography, Prenatal * methods   MeSH
• Bone Diseases, Developmental ultrasonography   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

X-viazaná hypofosfatémia (XLH) je najčastejšia hereditárna hypofosfatémia s prevalenciou 1/20 000. Ochorenie postihuje rovnako obidve pohlavia. XLH sa manifestuje v detstve s typickými klinickými prejavmi rachitídy, ako je krátka postava, bolesti kostí a deformity skeletu. Ochorenie je charakterizované laboratórnym nálezom chronickej hypofosfatémie, normokalciémie a normálnymi a/alebo iba mierne zvýšenými koncentráciami PTH. Príčinou XLH je mutácia PHEX génu (fosfát regulujúca endopeptidáza). Mutácie PHEX génu vedú k signifikantne zvýšenej cirkulujúcej koncentrácií FGF23, ktorý je regulačný hormón (fosfatonín), čo má za následok zníženú tubulárnu reabsorpciu fosfátov a poruchu mineralizácie kostí. Konvenčná liečba suplementáciou fosforom a kalcitriolom môže byť u niektorých jedincov sčasti účinná, ale má významné vedľajšie účinky. Dnes je už dostupná cielená patogenetická liečba monoklonálnou protilátkou (burosumab), ktorá viaže nadbytok FGF-23 v cirkulácií a tým priamo zasahuje do patogenetického mechanizmu ochorenia. V článku sú opísané vzácne prípady 2 detí s X-viazanou hypofosfatemickou rachitídou úspešne liečených burosumabom.

X-linked hypophosphataemia (XLH) is the most common hereditary hypophosphataemia with a prevalence of 1:20,000. The disease affects both sexes equally. XLH is manifested in childhood with typical clinical signs of rickets such as short stature, bone pain and skeletal deformities. The disease is characterized by the laboratory finding of chronic hypophosphatemia, normocalcemia and normal and/or only slightly elevated PTH. The cause of XLH is a mutation in the PHEX gene (phosphate regulating endopeptitase). Mutations in the PHEX gene lead to significantly increased circulating concentrations of FGF23, a regulatory hormone (phosphatonin), resulting in decreased tubular phosphate reabsorption and impaired bone mineralization. Conventional treatment with phosphorus and calcitriol supplementation may be partially effective in some individuals, but has significant side effects. Targeted pathogenetic treatment with a monoclonal antibody (burosumab) is now available, which binds excess FGF-23 in the circulation and thus directly interferes with the pathogenetic mechanism of the disease. We describe two rare cases of X-linked hypophosphatemic rickets successfully treated with burosumab.

• Keywords
• Burosumab,
• MeSH
• Lower Extremity physiopathology   MeSH
• Familial Hypophosphatemic Rickets * diagnosis   drug therapy   physiopathology   MeSH
• Fibroblast Growth Factor-23 antagonists & inhibitors   metabolism   adverse effects   MeSH
• Antibodies, Monoclonal, Humanized administration & dosage   therapeutic use   MeSH
• Humans MeSH
• Child, Preschool MeSH
• Check Tag
• Humans MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Genetic Diseases, Inborn prevention & control   MeSH
• Genetics, Medical MeSH
• Chromosomes, Human, X MeSH
• Sex Chromosomes MeSH
• Sex Chromosome Disorders genetics   MeSH
• Publication type
• Congress MeSH
• Collected Work MeSH

• Conspectus
• Obecná genetika. Obecná cytogenetika. Evoluce
• NML Fields
• genetika, lékařská genetika

Mutace v MTM1 genu způsobují X-vázanou myotubulární myopatii (XLMTM). Jedná se o závažné, většinou časně letální onemocnění. Popisujeme dva chlapce, dvojčata s molekulárně geneticky prokázanou XLMTM. Chlapci se narodili ve 28. týdnu gravidity, nápadná byla těžká hypotonie a slabost s areflexií, od narození byla nutná intenzivní péče včetně umělé plicní ventilace. Progredující oběhová a renální nedostatečnost byla u obou důvodem ukončení péče po 26, resp. 35 dnech přežívání. Ve svalové excizi byla nalezena hypotrofická svalová vlákna a fetální myotuby spolu s četnými centrálně lokalizovanými jádry. To vše vedlo k podezření na XLMTM, které jsme následně potvrdili molekulárně geneticky nálezem mutace c.82delA ve třetím exonu MTM1 genu. Stejná mutace, v heterozygotním stavu, byla následně prokázána i u matky pacientů. Pravděpodobně se jedná o první případ tohoto onemocnění molekulárně geneticky potvrzeného v ČR. Rodině můžeme nabídnout cílenou genetickou prevenci v podobě prenatální nebo preimplantační diagnostiky. Zavedení vyšetření MTM1 genu může být využito u dalších rodin s buď již dříve klinicky stanovenou dg. XLMTM, nebo pro nově diagnostikované rodiny. Klíčová slova: MTM1 gen – myotubulární myopatie – mutace vedoucí k posunu čtecího rámce

Mutations in the MTM1 gene cause X-linked myotubular myopathy (XLMTM). This is a se­rious, often lethal, condition. We report a family with two affected children – dizygotic twins. Boys were born in the 28th gestational week. Severe hypotonia and muscle weakness were present at birth and necessitated ventilatory support. Intensive care was terminated 26 and 35 days after birth, respectively, due to cardiac and renal failure. Hypotrophic muscle fibers, fetal myotubes and centrally located nuclei were present in muscle sections. All the available information led us to the diagnosis of XLMTM. The MTM1 gene was sequenced and a novel mutation c.82delA in exon 3 was identified. The mother of the patients is a heterozygous carrier of the mutation. This might well be the first report of genetically confirmed XLMTM in the Czech Republic. DNA test is now available and prenatal or preimplantation diagnosis might be offered to the family. Key words: MTM1 gene – myotubular myopathy – frameshift mutation

• Keywords
• mutace vedoucí k posunu čtecího rámce,
• MeSH
• Gene Deletion MeSH
• Twins MeSH
• Genetic Linkage MeSH
• Genetic Diseases, X-Linked genetics   MeSH
• Genetic Diseases, Inborn MeSH
• Genetic Testing MeSH
• Genotype MeSH
• Heterozygote MeSH
• Labor, Induced MeSH
• Intensive Care, Neonatal MeSH
• Muscle, Skeletal pathology   MeSH
• Humans MeSH
• Chromosomes, Human, X MeSH
• Mutation genetics   MeSH
• DNA Mutational Analysis MeSH
• Myopathies, Structural, Congenital * genetics   MeSH
• Protein Tyrosine Phosphatases, Non-Receptor * genetics   MeSH
• Infant, Premature MeSH
• Infant, Newborn MeSH
• Perinatal Care MeSH
• Frameshift Mutation * genetics   MeSH
• Premature Birth MeSH
• Respiratory Insufficiency MeSH
• Pedigree MeSH
• Muscle Hypotonia etiology   MeSH
• Family Health MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Publication type
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH

Patogenní varianty v genu ABCD1 jsou genetickou příčinou X­‐vázané adrenoleukodystrofie (X­‐ALD). X­‐ALD se může manifestovat jako závažná letální adrenoleukodystrofie (ALD), mírnější adrenomyeloneuropatie (AMN) nebo adrenální insuficience (Addisonova nemoc), ale může se klinicky projevit jen jako mírná spastická paraparéza, zejména u žen přenašeček. Během několika let genetické diagnostiky dědičných spastických paraparéz (HSP) byly diagnostikovány čtyři české rodiny s patogenní variantou v genu ABCD1, kdy byl některý ze členů rodiny odeslán k vyšetření genů spojovaných s hereditární spastickou paraparézou, která byla jediným klinickým projevem nemoci, někdy dokonce u více členů rodiny. Až na základě genetické diagnostiky a po nalezení kauzální patogenní varianty v genu ABCD1 bylo možné zpětně správně stanovit diagnózu některých příslušníků rodin, neboť byli vedeni (případně i zemřeli) s diagnózou roztroušená skleróza, nemoci motoneuronu aj. Znalost kauzální patogenní varianty je velmi důležitá a na jejím základě lze pak v rodině stanovit riziko zejména pro mužské jedince, protože u nich vzhledem k X-vázané dědičnosti hrozí závažný až fatální průběh onemocnění. X­‐vázaná dědičnost v rodině, mírnější klinické projevy v podobě spastické paraparézy u žen a projevy ALD, AMN nebo adrenální insuficience (Addisonova nemoc) u mužů v rodině mohou být dobrým vodítkem při podezření na tuto diagnózu. Počet takových rodin může být v ČR mnohem vyšší. Jedním z klinických projevů a biochemickým ukazatelem onemocnění jsou vysoké hladiny mastných kyselin s velmi dlouhým řetězcem (VLCFA) v krevním séru, které jsou jednoduše diagnostikovatelné. Pro genetické potvrzení diagnózy jsou k dispozici klasické i nové metody genomiky.

Pathogenic variants in the ABCD1 gene are the genetic cause of X-linked adrenoleukodystrophy (X-ALD). X-ALD can manifest as severe fatal adrenoleukodystrophy (ALD), milder adrenomyeloneuropathy (AMN), or adrenal insufficiency (Addison's disease), but it can present clinically only as mild spastic paraparesis, particularly in female carriers. During several years of genetically diagnosing hereditary spastic paraparesis (HSP), four Czech families were diagnosed with a pathogenic variant in the ABCD1 gene when one of the family members was referred for testing of genes associated with hereditary spastic paraparesis that was the only clinical manifestation of the disease, sometimes even in several family members. Only on the basis of genetic diagnosis and after identification of the causative pathogenic variant in the ABCD1 gene, it was possible to retrospectively determine the correct diagnosis of some family members, as they had been diagnosed (or died) with multiple sclerosis, motor neurone disease, and others. The knowledge of the causative pathogenic variant is very important and it is on its basis that the risk can be determined in the family, particularly for male individuals because they are at risk of severe to fatal course of the disease due to X-linked inheritance. X-linked inheritance in the family, milder clinical manifestations in the form of spastic paraparesis in women, and manifestations of ALD, AMN, or adrenal insufficiency (Addison's disease) in male family members can all be good clues to lead one to suspect this diagnosis. The number of such families may be much higher in the Czech Republic. One of the clinical manifestations and biochemical markers of the disease are high levels of very long-chain fatty acids (VLCFA) in the blood serum which are easy to diagnose. Classic as well as novel methods of genomics are available for genetic confirmation of the diagnosis.

• MeSH
• Adrenoleukodystrophy * diagnostic imaging   classification   pathology   therapy   MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Fatty Acids analysis   MeSH
• Paraparesis, Spastic * diagnosis   etiology   genetics   MeSH
• Age Factors MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Kongenitálna adrenálna hypoplázia (AHC) je X-viazané ochorenie, charakteristické soľnou poruchou krátko po narodení, primárnou adrenálnou insuficienciou v detstve a chýbajúcim nástupom puberty v dôsledku hypogonadotropného hypogonadizmu (HH). Doteraz popísané mutácie DAX-1 génu u pacientov s AHC a HH zahŕňajú substitúcie nukleotidov (missense/nonsense), malé delécie, inzercie a indely, veľké delécie ako aj komplexné preskupenia. V práci popisujeme klinické príznaky, výsledky laboratórnych a hormonálnych vyšetrení a výsledky molekulárnej analýzy u mužského probanda so suspektnou X-viazanou AHC. Sekvenčná analýza u pacienta potvrdila inzerciu dvoch nukleotidov (cytozínu a guanínu) v kodóne 141 prvého exónu DAX-1 génu. Mutácia viedla k úplne odlišnému sledu aminokyselín od kodónu 141 až do predčasného stop kodónu ACT na pozícii 177. Podľa očakávania, matka pacienta bola heterozygotnou prenášačkou mutácie, zatiaľ čo sestra pacienta je zdravá. Prípad zdôrazňuje význam genetického testovania pacientov s primárnou adrenálnou insuficienciou a podozrením na X-viazanú formu AHC. Príznačným je nález hoci i parciálneho deficitu gonadotropínov u postihnutých mužských pacientov. Skoré rozpoznanie diagnózy AHC u pacienta, ktoré môže byť potvrdené analýzou na prítomnosť mutácie v DAX-1 géne, je dôležité pre predchádzanie následkov oneskorenej substitučnej liečby androgénmi, ako aj pre genetické poradenstvo v postihnutej rodine.

Adrenal hypoplasia congenita (AHC) is an X-linked disorder, characterized by salt-losing crisis in the neonatal period, primary adrenal insufficiency during infancy and failure to undergo puberty because of hypogonadotropic hypogonadism (HH). Different mutations types of the DAX-1 gene have been reported in patients with AHC and HH, including nucleotide substitutions (missense/nonsense), small deletions, insertions and indels, gross deletions as well as complex rearrangements. In this report, we describe the clinical features, the laboratory and hormonal findings and the results of mutational analysis in proband male patient with suspected X-linked AHC. Sequence analysis of the patient´s DAX-1 gene demonstrated a 2-bp (CG) insertion at codon 141 in exon 1. The mutation shifts the reading frame, resulting in completely different amino acid sequences from codon 141 to the premature stop codon ACT at amino acid 177. As expected, the patient´s mother was a heterozygous carrier for the mutation, whereas his sister did not carry the mutation. This case emphasizes the value of genetic testing in boys with primary adrenal insufficiency and suspected X-linked AHC. The findings of even partial gonadotropic deficiency in the affected males is notable and early recognition of such a possibility in a patient, which may be facilated by DAX-1 mutational analysis, may help to prevent the sequelee of delayed androgen replacement therapy, as well as for genetic counseling in the affected family.

• MeSH
• Adrenal Insufficiency diagnosis   pathology   therapy   MeSH
• Adult MeSH
• Genetic Diseases, Inborn diagnosis   pathology   therapy   MeSH
• Hypogonadism genetics   pathology   therapy   MeSH
• Humans MeSH
• Mutation MeSH
• Testicular Diseases pathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

The aim of this study was to identify RS1 pathogenic variants in Czech patients with X-linked retinoschisis (XLRS) and to describe the associated phenotypes, including natural history, in some cases. Twenty-one affected males from 17 families were included. The coding region of RS1 was directly sequenced and segregation of the identified mutations was performed in available family members. In total, 12 disease-causing variants within RS1 were identified; of these c.20del, c.275G>A, c.[375_379del; 386A>T], c.539C>A and c.575_576insT were novel, all predicted to be null alleles. The c.539C>A mutation occurred de novo. Three patients (aged 8, 11 and 19 years) were misdiagnosed as having intermediate uveitis and treated with systemic steroids. Repeat spectral domain optical coherence tomography examinations in four eyes documented the transition from cystoid macular lesions to macular atrophy in the fourth decade of life. Four individuals were treated with topical dorzolamide and in two of them, complete resolution of the cystic macular lesions bilaterally was achieved, while one patient was noncompliant. Rebound phenomenon after discontinuation of dorzolamide for 7 days was documented in one case. Misdiagnosis of XLRS for uveitis is not uncommon; therefore, identification of disease-causing variants is of considerable benefit to the affected individuals.

• MeSH
• Antihypertensive Agents administration & dosage   therapeutic use   MeSH
• Child MeSH
• Gene Frequency MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Mutation MeSH
• Eye Proteins genetics   MeSH
• Tomography, Optical Coherence MeSH
• Child, Preschool MeSH
• Retinoschisis drug therapy   genetics   pathology   MeSH
• Pedigree MeSH
• Sulfonamides administration & dosage   therapeutic use   MeSH
• Thiophenes administration & dosage   therapeutic use   MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Child, Preschool MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH