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A R Janecke

Publications and source records attributed to A R Janecke.

13 recordsLinked to original sources
PubMed2005

Mutation spectrum of type I glycogen storage disease in Hungary.

We performed mutation analysis in 12 Hungarian type I glycogen storage disease (GSD I) patients in order to determine the mutation spectrum. All patients were clinically classified as GSD Ia. Nine patients carried biallelic G6PC mutations (p.Q27fsX35, p.D38V, p.W70X, p.K76N, p.W77R, p.R83C, p.E110Q, p.G222R), with E110Q reported only in Hungary. However, three patients displayed two common G6PT1 (SLC37A4) mutations (p.L348fsX400, p.C183R) which were originally described in association with GSD Inon-a. Review of the literature and our data show that G6PT1 mutations are not associated with neutropenia and related clinical findings in approximately 10% of these cases. Homozygosity for the truncating G6PT1 mutation p.L348fsX400 can be observed with and without neutropenia, indicating that one or more modifiers of the action of G6PT1 exist. Our data are suitable to provide DNA-based and thus noninvasive confirmation of diagnosis in Hungarian patients with this disorder.

Age of Onset↗
PubMed2005

Ocular manifestations of keratitis-ichthyosis-deafness (KID) syndrome.

OBJECTIVE: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal dysplasia characterized by the association of hyperkeratotic skin lesions, moderate to profound sensorineural hearing loss and vascularizing keratitis. Mutations in the GJB2 gene coding for connexin 26, a component of gap junctions in epithelial cells, have been observed in several KID patients. Variable ocular manifestations of the disease in 3 patients with molecular genetically confirmed KID syndrome are reported. DESIGN: Retrospective case series. METHODS: Clinical examination and molecular genetic analysis for mutations in the GJB2 gene were performed in 3 patients with KID syndrome ages 5, 13, and 41 years. RESULTS: Visual acuity ranged from normal to severe visual loss. The ocular signs included loss of eyebrows and lashes, thickened and keratinized lids, trichiasis, recurrent corneal epithelial defects, superficial and deep corneal stromal vascularization with scarring, keratoconjunctivitis sicca, and, in one patient, presumed limbal insufficiency. Whereas ocular surface integrity could be maintained with artificial tears in one patient, and an epithelial defect healed under conservative treatment in the second patient, multiple surgical procedures including superficial keratectomies, limbal allograft transplantation with systemic immunosuppression, amniotic membrane transplantation, lateral tarsorrhaphies, and lamellar keratoplasty could not preserve useful vision in the third patient. CONCLUSIONS: KID syndrome may affect the ocular adnexae and surface with variable severity independent of the age of the patient. Lid abnormalities, corneal surface instability, limbal stem cell deficiency with resulting corneal complications, and dry eye are the main ocular manifestations.

Adolescent↗
PubMed2005

Novel rhodopsin mutations and genotype-phenotype correlation in patients with autosomal dominant retinitis pigmentosa.

AIM: To identify novel or rare rhodopsin gene mutations in patients with autosomal dominant retinitis pigmentosa and description of their clinical phenotype. METHODS: The complete rhodopsin gene was screened for mutations by DNA sequencing in index patients. Mutation specific assays were used for segregation analysis and screening for controls. Eight patients from five families and their relatives were diagnosed with autosomal dominant retinitis pigmentosa (adRP) by means of clinical evaluation. RESULTS: Mutation screening identified five different rhodopsin mutations including three novel mutations: Ser176Phe, Arg314fs16, and Val20Gly and two missense mutations, Pro215Leu and Thr289Pro, that were only reported once in a mutation report. Electrophysiological and psychophysical testings provide evidence of an impaired rod system with additionally affected cone system in subjects from each genotype group. Visual function tended to be less affected in subjects with the Arg314fs16 and Val20Gly mutations than in the Ser176Phe phenotype. In contrast, Pro215Leu and Thr289Pro mutations caused a remarkably severe phenotype. CONCLUSION: The ophthalmic findings support a correlation between disease expression and structural alteration: (1) extracellular/intradiscal Val20Gly and cytoplasmic Arg314fs16 mutation-mild adRP phenotype; (2) Ser176Phe mutation-"mostly type 1" disease; (3) predicted alteration of transmembrane domains TM V and TM VII induced by Pro215Leu and Thr289Pro-severe phenotype. However, variation of phenotype expression in identical genotypes may still be a typical feature of RHO mutations.

Adolescent↗
PubMed2001

Molecular genetics of type 1 glycogen storage disease.

Glycogen storage disease type 1 (GSD 1) comprises a group of autosomal recessive inherited metabolic disorders caused by deficiency of the microsomal multicomponent glucose-6-phosphatase system. Of the two known transmembrane proteins of the system, malfunction of the catalytic subunit (G6Pase) characterizes GSD 1a. GSD 1 non-a is characterized by defective microsomal glucose-6-phosphate or pyrophosphate/phosphate transport due to mutations in G6PT (glucose-6-phosphate translocase gene) encoding a microsomal transporter protein. Mutations in G6Pase and G6PT account for approximately 80 and approximately 20% of GSD 1 cases, respectively. G6Pase and G6PT work in concert to maintain glucose homeostasis in gluconeogenic organs. Whereas G6Pase is exclusively expressed in gluconeogenic cells, G6PT is ubiquitously expressed and its deficiency generally causes a more severe phenotype. Rapid confirmation of clinically suspected diagnosis of GSD 1, reliable carrier testing, and prenatal diagnosis are facilitated by mutation analyses of the chromosome 11-bound G6PT gene as well as the chromosome 17-bound G6Pase gene.

Antiporters↗
PubMed2001

De novo mutation of the connexin 26 gene associated with dominant non-syndromic sensorineural hearing loss.

Mutations of the connexin 26 (Cx26) gene cause isolated recessive or dominant hearing loss or both sensorineural hearing impairment and keratoderma. We have identified the first de novo mutation of the Cx26 gene, R75 W, in a sporadic case of isolated profound hearing loss. R75 W has been previously observed in association with hearing impairment and keratoderma in one family and is thus thought to cause both syndromic and non-syndromic hearing loss. This case illustrates the risk of a possible erroneous diagnosis of autosomal recessive hearing loss in a sporadic case.

Amino Acid Substitution↗
PubMed2001

Sensorineural hearing loss and the incidence of Cx26 mutations in Austria.

A clinical evaluation and Cx26 mutation analysis was performed in 92 consecutive patients with sensorineural hearing loss in order to delineate the spectrum of genetically caused hearing loss. Among patients of Austrian origin, 53% were classified with hereditary hearing loss. Cx26 mutations were found in 26% of NSHL patients (40% of familial vs 18% of sporadic cases). The mutation 35delG accounted for 52.8% of all presumed GJB2 disease alleles. The second most frequent mutation was L90P (16.7%) having been reported with a prevalence of 0.7-3.5% in other populations. Three novel mutations were found. The novel mutation, R143Q, was associated with dominant high-frequency hearing loss. Pseudodominant transmission of NSHL was seen in four families with Cx26 mutations. A mutation 35delG carrier rate of 0.9% was observed among 672 controls from West-Austria. Cx26 mutations were found associated with mild to profound, and with asymmetric hearing impairment.

Austria↗
PubMed2000

Mutation analysis in glycogen storage disease type 1 non-a.

We report molecular and clinical findings in 13 patients with rare types of glycogen storage disease 1 (GSD1 non-a). Analysis of G6PT encoding a microsomal transporter protein has revealed mutations on both chromosomes in each case, four of which are novel. Diagnosis has been confirmed in three patients suspected of having GSD1 non-a without enzymatic studies involving liver biopsy, thus emphasising the advantage of G6PT mutation analysis for all GSD1 non-a patients.

Adolescent↗
PubMed1999

Twelve novel myosin VIIA mutations in 34 patients with Usher syndrome type I: confirmation of genetic heterogeneity.

Usher syndrome is a heterogeneous autosomal recessive trait and the most common cause of hereditary deaf-blindness. Usher syndrome type I (USH1) is characterised by profound congenital sensorineural hearing loss, vestibular dysfunction, and prepubertal onset of retinitis pigmentosa. Of the at least six different loci for USH1, USH1B maps on chromosome 11q13, and the MYO7A gene has been shown to be defective in USH1B. MYO7A encodes myosin VIIA, an unconventional myosin, and it consists of 48 coding exons. In this study, MYO7A was analysed in 34 unrelated Usher type I patients by single-strand conformation polymorphism analysis and direct sequencing. We identified a total of 12 novel and unique mutations, all single base changes. In addition, we found a previously reported nonsense mutation (C31X) on nine alleles of a total of six patients from Denmark.

Chromosome Mapping↗
PubMed1999

Molecular diagnosis of type 1c glycogen storage disease.

Glycogen storage disease type 1 (GSD 1) results from deficiency of the microsomal multicomponent glucose-6-phosphatase system. Malfunction of the catalytic subunit characterises GSD 1a. GSD 1b and GSD 1c are characterised by defective microsomal glucose-6-phosphate or pyrophosphate/phosphate transport, respectively. Recently, a gene encoding a microsomal transporter protein has been found to be mutated in GSD 1b and 1c patients. Here, we report the genomic sequence of the transporter gene and the detection of a homozygous 2-bp deletion (1211delCT) and a homozygous donor splice site mutation (317+1G-->T) in two GSD 1c patients, confirming that GSD 1c is allelic to GSD 1b.

Antiporters↗
PubMed1999

Increased energy expenditure and fecal fat excretion do not impair weight gain in small-for-gestational-age preterm infants.

In order to optimize the nutrition of high-risk premature infants beyond the early postnatal period, a more precise knowledge of individual nutritional requirements is needed. We therefore studied the influence of intrauterine growth retardation on energy expenditure and nutrient utilization determined by indirect calorimetry and fecal fat excretion (steatocrit) in nineteen premature infants who were appropriate-for-gestational-age (AGA; mean gestational age 29.9+/-0.3 weeks, mean birth weight 1.30+/-0.05 kg) and thirteen small-for-gestational-age (SGA) premature infants [mean gestational age 32.4+/-0.5 weeks, mean birth weight 1.024+/-0.07 kg (i.e., below the 10th percentile)] during the first and second month of life. All infants were clinically stable during the study period. In nine SGA infants we observed a significantly higher steatocrit compared to twelve AGA infants (29+/-1 vs. 17+/-1% p = 0.0001). SGA infants (n = 12) also showed a slightly (albeit statistically not significantly) higher energy expenditure than AGA infants (n = 15) (58.7+/-1.9 vs. 53.6+/-1.5 kcal/kg per day, p = 0.054). Despite the increased fat excretion and higher energy expenditure, SGA infants gained weight more rapidly during the study period than AGA infants (20+/-1 vs. 17+/-1 g/kg per day, p = 0.026). We conclude that influences of intrauterine growth retardation on energy expenditure and nutrient utilization persist during the first weeks of extrauterine life. However, these metabolic changes do not impair the capability of SGA infants for extrauterine catch-up growth if adequate nutrition is provided.

Aging↗
PubMedDate not supplied

[Application of indirect calorimetry in monitoring feeding of low birth-weight preterm infants].

BACKGROUND: We investigated the practical use of indirect calorimetry for the individual nutritional support of preterm infants in order to answer the question whether it is possible to reliably calculate energy expenditure, fat and carbohydrate oxidation in preterm infants individually by using the results of a timed 6-hour-measurement of oxygen consumption and carbon dioxide production. PATIENTS: Measurements were performed in 20 preterm infants (gestational age 30.2 +/- 0.6 weeks, birth weight 1.09 +/- 0.07; mean +/- SEM) at a mean postnatal age of 25 +/- 4 days and with a body weight of 1.35 +/- 0.06 kg. METHODS: Carbon dioxide production (24 h-VCO2), oxygen consumption (24 h-VO2) and respiratory quotient (24 h-RQ) were measured by indirect calorimetry for 24 hours using the Deltatrac II metabolic monitor (Datex, Helsinki, Finland). Additionally, 6 h-VCO2, 6 h-VO2 and 6 h-RQ were determined by measurement over 6 hours. The patients' energy expenditure, fat and carbohydrate oxidation were calculated from VCO2 and VO2 measured over a 24 hour- and 6 hour-period with or without consideration of urinary nitrogen excretion (NU). RESULTS: If NU was not included in the calculation of energy expenditure, the values differed by maximally 1.1% from the calculations including NU. The correlations between the 24 h-RQ and the calculated 24 h-fat or 24 h-carbohydrate oxidation values were statistically significant (r = -0.99; p = 0.0001 and r = 0.773; p = 0.0002 respectively). However, in individual patients, it was not possible to predict 24 h energy expenditure, fat and carbohydrate oxidation of preterm infants using values determined by 6 h indirect calorimetry. CONCLUSION: The determination of the urine-nitrogen excretion is not necessary for calculation of energy expenditure of preterm infants. It is possible to estimate fat and carbohydrate oxidation of preterm infants by the measured 24 h-RQ, but 6 h indirect calorimetry is not accurate enough for calculating the individual nutritional needs of preterm infants in clinical practice. Indirect calorimetry over 24 h may be helpful in the management of selected patients with nutritional problems.

Calorimetry, Indirect↗