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.

• Klíčová slova
• gene dosage, genetics of sex, lizard, qPCR, sex chromosomes, sex determination,
• MeSH
• genetická vazba MeSH
• genová dávka MeSH
• geny vázané na chromozom X * MeSH
• ještěři genetika   MeSH
• konzervovaná sekvence MeSH
• sexuální faktory MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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.

• Klíčová slova
• RS1, X-linked retinoschisis, novel variant, steroid treatment, uveitis,
• MeSH
• antihypertenziva aplikace a dávkování   terapeutické užití   MeSH
• dítě MeSH
• frekvence genu MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mutace MeSH
• oční proteiny genetika   MeSH
• optická koherentní tomografie MeSH
• předškolní dítě MeSH
• retinoschisis farmakoterapie   genetika   patologie   MeSH
• rodokmen MeSH
• sulfonamidy aplikace a dávkování   terapeutické užití   MeSH
• thiofeny aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antihypertenziva MeSH
• dorzolamide MeSH Prohlížeč
• oční proteiny MeSH
• RS1 protein, human MeSH Prohlížeč
• sulfonamidy MeSH
• thiofeny MeSH

X-linked agammaglobulinemia (XLA) was one of the first inborn errors of immunity to be described. It is caused by pathogenic variants in the gene for Bruton tyrosine kinase (BTK), which has important functions in B cell development and maturation. Recurrent bacterial infections in the first two years of life and hypogammaglobulinemia with absent B cells in male patients are the most common symptoms. A four-month-old male patient underwent surgical removal of urachus persistens complicated with recurrent scar abscesses. Hypogammaglobulinemia (IgG, IgA, and IgM), low phagocytic activity, mild neutropenia, and a normal percentage of B cells were observed in the patient's immune laboratory profile. Over time, he suffered recurrent respiratory infections (otitis media and rhinosinusitis) and developed B cell depletion, but interestingly, this was with a normalisation of IgG and IgA levels along with undetectable IgM. Molecular-genetic testing confirmed the presence of the pathogenic variant c.1843C>T in the BTK gene, which is associated with a milder phenotype of XLA. Molecular-genetic testing uncovers the variability of clinical and laboratory features of apparently well-known inherited disorders. Patients with mild "leaky" XLA may have normal levels of non-functional or oligoclonal immunoglobulins.

• Klíčová slova
• BTK gene, Inborn error of immunity, X-linked agammaglobulinemia, atypical leaky phenotype, molecular-genetic testing,
• MeSH
• agamaglobulinemie * genetika   diagnóza   MeSH
• genetické nemoci vázané na chromozom X * genetika   diagnóza   MeSH
• genetické testování * MeSH
• kojenec MeSH
• lidé MeSH
• proteinkinasa BTK * genetika   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• BTK protein, human MeSH Prohlížeč
• proteinkinasa BTK * MeSH

AIM: Primary immunodeficiencies (PID) are becoming a recognized public health problem worldwide. The most important subgroup of these disorders are the antibody deficiencies. X-linked agammaglobulinaemia was the first described entity of this group and is characterised by early onset of recurrent bacterial infections, profound deficiency of all immunoglobulin isotypes and markedly reduced number of peripheral B-lymphocytes. CASE REPORT: We report the case of a 10-year old boy with X-linked agammaglobulinaemia caused by a previously non-described mutation in BTK gene with typical clinical presentation but delayed diagnosis. Following diagnosis, substitution therapy with intravenous immunoglobulins was started and the clinical status of the patient improved. CONCLUSION: We reported a case of X-linked agammaglobulinaemia with delayed diagnosis despite the typical anamnestic signs for primary humoral immunodeficiency. The disease was caused by a previously non-reported mutation in the BTK gene. Measurement of serum immunoglobulins should be performed in all children with recurrent, complicated respiratory infections as a screening test for humoral immunodeficiencies.

• MeSH
• agamaglobulinemie farmakoterapie   genetika   MeSH
• dítě MeSH
• genetické nemoci vázané na chromozom X farmakoterapie   genetika   MeSH
• intravenózní imunoglobuliny terapeutické užití   MeSH
• lidé MeSH
• mutace * MeSH
• proteinkinasa BTK MeSH
• tyrosinkinasy genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• BTK protein, human MeSH Prohlížeč
• intravenózní imunoglobuliny MeSH
• proteinkinasa BTK MeSH
• tyrosinkinasy MeSH

PURPOSE: The aim of the study was to describe the phenotype and molecular genetic causes of X-linked megalocornea (MGC1). We recruited four British, one New Zealand, one Vietnamese and four Czech families. METHODS: All probands and three female carriers underwent ocular examination and Sanger sequencing of the CHRDL1 gene. Two of the probands also had magnetic resonance imaging (MRI) of the brain. RESULTS: We identified nine pathogenic or likely pathogenic and one variant of uncertain significance in CHRDL1, of which eight are novel. Three probands had ocular findings that have not previously been associated with MGC1, namely pigmentary glaucoma, unilateral posterior corneal vesicles, unilateral keratoconus and unilateral Fuchs heterochromic iridocyclitis. The corneal diameters of the three heterozygous carriers were normal, but two had abnormally thin corneas, and one of these was also diagnosed with unilateral keratoconus. Brain MRI identified arachnoid cysts in both probands, one also had a neuroepithelial cyst, while the second had a midsagittal neurodevelopmental abnormality (cavum septum pellucidum et vergae). CONCLUSION: The study expands the spectrum of pathogenic variants and the ocular and brain abnormalities that have been identified in individuals with MGC1. Reduced corneal thickness may represent a mild phenotypic feature in some heterozygous female carriers of CHRDL1 pathogenic variants.

• Klíčová slova
• CHRDL1, brain MRI, heterozygous carriers, keratoconus, megalocornea, posterior corneal vesicles,
• MeSH
• dědičné nemoci očí * diagnóza   MeSH
• fenotyp MeSH
• genetické nemoci vázané na chromozom X * diagnóza   genetika   MeSH
• keratokonus * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Chondrodysplasia punctata represents clinically and genetically a heterogeneous group of disorders characterized by the presence of multiple congenital anomalies and stippled epiphyses. We present clinical course of the disease and the results of metabolic, X-ray and molecular analyses in 19-months old girl with X-linked dominant chondrodysplasia punctata with intrauterine growth retardation, craniofacial dysmorphy, cataracts, cutaneous anomalies including ichthyosis, asymmetric rhizomesomelic shortness of the limbs, deformity of the spine, club foot, polydactyly, syndactyly, epiphyseal stippling and low cholesterol (2.29 mmol/l). Spectrophotometric analysis revealed the presence of abnormal pattern of cholesterol precursors in blood. The increased level of 8-dehydrocholesterol (42.2 micromol/l, controls < 1) and 7-dehydrocholesterol (25.5 micromol/l, controls < 1) recognised with GC/MS suggested an endogenous defect of cholesterol biosynthesis. The diagnosis of X-linked dominant chondrodysplasia punctata (CDPX2) was confirmed by the molecular analysis. Sequencing of the EBP gene encoding for 3beta-hydroxysteroid-delta8,delta7-isomerase revealed the presence of "de novo" heterozygous mutation c.327C>T (p.Arg110Stop). High cholesterol diet normalized cholesterol level (3.28 mmol/l) but it had no influence on the unfavourable prognosis of the disease. Low level of cholesterol with abnormal sterol profile in a child with congenital development anomalies represent an important laboratory marker suggesting an inherited defect of cholesterol biosynthesis.

• MeSH
• cholesterol biosyntéza   MeSH
• chondrodysplasia punctata vrozené   genetika   metabolismus   MeSH
• genetické nemoci vázané na chromozom X * MeSH
• kojenec MeSH
• lidé MeSH
• vrozené poruchy metabolismu tuků genetika   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cholesterol MeSH

BACKGROUND: Hypertrophic cardiomyopathy with severe left ventricular diastolic dysfunction has been associated with marked exercise intolerance and poor prognosis. However, molecular pathogenesis of this phenotype remains unexplained in a large proportion of cases. METHODS AND RESULTS: We performed whole exome sequencing as an initial genetic test in a large Czech family with 3 males affected by nonobstructive hypertrophic cardiomyopathy with severe left ventricular diastolic dysfunction in end-stage disease. A novel frameshift mutation of four-and-a-half LIM domain 1 gene (FHL1) (c.599_600insT; p.F200fs32X) was detected in these individuals. The mutation does not affect transcription, splicing, and stability of FHL1 mRNA and results in production of truncated FHL1 protein, which is contrary to heart tissue homogenate not detectable in frozen tissue sections of myocardial biopsy of affected males. The identified mutation cosegregated also with abnormal ECG and with 1 case of apical hypertrophic cardiomyopathy in heterozygous females. Although skeletal muscle involvement is a common finding in FHL1-related diseases, we could exclude myopathy in all mutation carriers. CONCLUSIONS: We identified a novel FHL1 mutation causing isolated hypertrophic cardiomyopathy with X-chromosomal inheritance.

• Klíčová slova
• cardiomyopathy, hypertrophic, exome, heart failure, diastolic,
• MeSH
• dospělí MeSH
• elektrokardiografie MeSH
• elektronová mikroskopie MeSH
• genetická predispozice k nemoci genetika   MeSH
• geny vázané na chromozom X genetika   MeSH
• hypertrofická kardiomyopatie genetika   metabolismus   patofyziologie   MeSH
• imunohistochemie MeSH
• intracelulární signální peptidy a proteiny genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mutace * MeSH
• myokard metabolismus   patologie   ultrastruktura   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proteiny s doménou LIM genetika   metabolismus   MeSH
• rodokmen MeSH
• senioři nad 80 let MeSH
• svalové proteiny genetika   metabolismus   MeSH
• zdraví rodiny MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• FHL1 protein, human MeSH Prohlížeč
• intracelulární signální peptidy a proteiny MeSH
• proteiny s doménou LIM MeSH
• svalové proteiny MeSH

BACKGROUND/AIMS: Congenital sideroblastic anemias (SA) are characterized by the presence of ringed sideroblasts in the bone marrow. The most common form is X-linked SA, which results from mutations in erythroid-specific δ-aminolevulinate synthase (ALAS2), the first enzyme in heme biosynthesis. In addition, autosomal recessive mutations in the erythroid-specific mitochondrial transporter SLC25A38 and glutaredoxin 5 (GLRX5) have recently been identified in SA patients with isolated erythroid phenotype. MATERIALS AND METHODS: We studied 5 young males with congenital SA from the Czech Republic. Mutation analysis was performed on the complete coding regions of 3 candidate genes (ALAS2, SLC25A38 and GLRX5), and the enzyme activity of ALAS2 was measured by a continuous spectrophotometric assay. RESULTS: We found the previously published R452H and R452C ALAS2 mutations in 3 patients. A novel K156E substitution in ALAS2 was discovered in 1 pyridoxine-responsive patient. The functional study showed that this substitution severely decreases ALAS2 enzyme activity. In 1 pyridoxine-refractory patient, no mutations were detected in ALAS2, SLC25A38 or GLRX5. CONCLUSION: Our report extends the list of known ALAS2 mutations, with the addition of a novel K156E substitution that is responsive to pyridoxine treatment and contributes to the general knowledge of congenital SA cases characterized worldwide.

• MeSH
• 5-aminolevulátsynthetasa genetika   metabolismus   MeSH
• dospělí MeSH
• genetické nemoci vázané na chromozom X MeSH
• lidé MeSH
• mutace MeSH
• pyridoxin terapeutické užití   MeSH
• sekvence nukleotidů MeSH
• sekvenční seřazení MeSH
• sideroblastická anemie farmakoterapie   enzymologie   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 5-aminolevulátsynthetasa MeSH
• ALAS2 protein, human MeSH Prohlížeč
• pyridoxin MeSH

• MeSH
• amplifikace genu MeSH
• běloši MeSH
• genetické nemoci vázané na chromozom X genetika   MeSH
• genotyp MeSH
• lidé MeSH
• mikrosatelitní repetice MeSH
• molekulární biologie MeSH
• mutace genetika   MeSH
• oční proteiny genetika   MeSH
• polymerázová řetězová reakce MeSH
• retinopathia pigmentosa genetika   MeSH
• rodokmen MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• oční proteiny MeSH
• RPGR protein, human MeSH Prohlížeč

An association between movement disorders and immune-system dysfunction has been described in the context of rare genetic diseases such as ataxia telangiectasia as well as infectious encephalopathies. We encountered a male patient who presented immunodeficiency of unknown etiology since childhood. A medication-refractory, progressive choreodystonic movement disorder emerged at the age of 42 years and prompted an exome-wide molecular testing approach. This revealed a pathogenic hemizygous variant in CD40LG, the gene implicated in X-linked hyper-IgM syndrome. Only two prior reports have specifically suggested a causal relationship between CD40LG mutations and involuntary hyperkinetic movements. Our findings thus confirm the existence of a particular CD40LG-related condition, combining features of compromised immunity with neurodegenerative movement abnormalities. Establishing the diagnosis is crucial because of potential life-threatening immunological complications.

• MeSH
• dítě MeSH
• dospělí MeSH
• imunodeficience s hyper-IgM, typ 1 * genetika   patologie   MeSH
• lidé MeSH
• ligand CD40 genetika   MeSH
• mutace MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ligand CD40 MeSH