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P Strømme

Publications and source records attributed to P Strømme.

At least 19 recordsLinked to original sources
PubMed2006

A novel splice site mutation in the Cockayne syndrome group A gene in two siblings with Cockayne syndrome.

Cockayne syndrome (CS) is mainly caused by mutations in the Cockayne syndrome group A or B (CSA or CSB) genes which are required for a sub-pathway of nucleotide excision repair entitled transcription coupled repair. Approximately 20% of the CS patients have mutations in CSA, which encodes a 44 kDa tryptophane (Trp, W) and aspartic acid (Asp, D) amino acids (WD) repeat protein. Up to now, nine different CSA mutations have been identified. We examined two Somali siblings 9 and 12 years old with clinical features typical of CS including skin photosensitivity, progressive ataxia, spasticity, hearing loss, central and peripheral demyelination and intracranial calcifications. Molecular analysis showed a novel splice acceptor site mutation, a G to A transition in the -1 position of intervening sequence 6 (g.IVS6-1G>A), in the CSA (excision repair cross-complementing 8 (ERCC8)) gene. IVS6-1G>A results in a new 28 amino acid C-terminus and premature termination of the CSA protein (G184DFs28X). A review of the CSA protein and the 10 known CSA mutations is also presented.

Amino Acid Sequence↗
PubMed2003

Brain cysts associated with mutation in the Aristaless related homeobox gene, ARX.

The novel Aristaless related homeobox gene, ARX, is widely expressed in the brain and is thought to play a key role in the regulation of brain development. Neurological phenotypes caused by ARX mutations have recently started to unfold. We describe a 72 year old man with X-linked mental retardation due to a 24 bp duplication mutation in exon 2 of the ARX gene. Cerebral MRI showed bilateral cystic-like cavities in both the cerebral and cerebellar hemispheres. No retraction or expansion in neighbouring parenchyma was observed, there was no history of acute neurological impairment, and no risk factors for cerebrovascular disease were found. The lesions appeared to be congenital and represented benign developmental cysts, possibly caused by the ARX mutation.

Aged↗
PubMed2001

Levels of cognitive and linguistic development in Angelman syndrome: a study of 20 children.

Angelman syndrome (AS) is a genetic disorder associated with severe developmental delay. The purpose of this study was to investigate cognitive and linguistic development in AS. Piaget's developmental model was used to evaluate the test results. The participants comprised 20 children (14 boys and 6 girls) aged 2-14 years (median age 7.4 years). AS was diagnosed either according to typical clinical criteria or confirmatory genetic testing. Cognitive functioning was evaluated with Griffiths' Mental Development Scale. Language development was also evaluated with Receptive-Expressive Emergent Language Scale 2 (REEL-2). Cognitive functioning, based on results on the Performance Scale, never exceeded Piaget's sensorimotor stage, 0-2 years. The median mental age for language development was 9 months. Expressive verbal vocabulary consisted of less than 2 words (n = 11), 2-3 words (n = 7) and 4-5 words (n = 2). Analyses according to REEL-2 did not indicate a consistent discrepancy between impressive and expressive language.

Adolescent↗
PubMed2000

Correlations between socioeconomic status, IQ and aetiology in mental retardation: a population-based study of Norwegian children.

BACKGROUND: Mental retardation (MR) (IQ< or = 70) is one of the most frequent and debilitating neurological handicaps in children. The aetiologies of MR are multiple and to a certain extent related to social class and the degree of MR. However, recent epidemiological data assessing these relationships are scarce. The objective of the present study was therefore to estimate the associations between socioeconomic status (SES), level of IQ, and causative factors in children with MR. METHODS: The investigation was designed as a cross-sectional population-based study of Akershus County, outside Norway's capital Oslo. The source population comprised 30 037 children born between 1980 and 1985. Of 178 children aged 8-13 years, 79 had severe MR (SMR) (IQ<50) and 99 had mild MR (MMR) (IQ 50-70). SES was grouped from I to V according to parental education. Diagnostic work-up regarding aetiology and medical diagnoses was extensive. The aetiology of MR was divided into two main groups: biopathological MR (n = 143), and unspecified MR, meaning MR of unknown aetiology (n = 35). Biopathological MR was further subdivided into four sub-groups: prenatal, perinatal, postnatal and undetermined timing of the damaging event. RESULTS: SES III, IV and V (the lower grades) increased the risk of MMR. In SES IV and V there was an increased risk of unspecified MR, odds ratio 7.0 and 5.6 (95% CI 1.3, 39.0 and 1.1, 30.0) respectively, compared to SES I. IQ in unspecified MR was significantly higher than in the biopathological aetiology sub-groups. CONCLUSIONS: The study showed that parents of children with SMR had a higher socioeconomic level than parents of children with MMR. The findings were also consistent with a partial overlap between unspecified MR and the lower end of normal IQ distribution in the general population.

Adolescent↗
PubMed2000

Aetiology in severe and mild mental retardation: a population-based study of Norwegian children.

The aetiology of mental retardation (MR) was studied in a population-based series of Norwegian children derived from 30 037 children born between 1980 and 1985. The study included 178 children, 79 with severe MR (SMR) (IQ<50) and 99 with mild MR (MMR) (IQ 50 to 70). Aetiology was divided into two main groups: biopathological and unspecified. The biopathological group comprised 96% of SMR and 68% of MMR, and was subdivided into prenatal (70% and 51%), perinatal (4% and 5%), and postnatal damage (5% and 1%), and a group of undetermined timing of the damaging event (18% and 11%). Single-gene disorders accounted for 15 of the 63 children with genetic disorders, including X-linked recessive in six. During the course of the study, at least 27 (15%) children had their aetiological diagnosis revised. Gestational age <32 weeks, birthweight <1500 g, and Apgar scores 0 to 2 at 1 and 5 minutes implied a significantly increased risk of MR, but contributed to only 4% of the children in the study. Decreased birthweight (1500 to 2499 g) and Apgar scores 3 to 6 at 1 and 5 minutes showed increased probability of MR. Despite extensive investigations, 4% of SMR and 32% of MMR were not identified with any biological markers and were considered as unspecified MR, several most probably representing the lower end of the normal IQ distribution in the population.

Adolescent↗
PubMed2000

Prevalence of psychiatric diagnoses in children with mental retardation: data from a population-based study.

The main purpose of the study was to estimate the prevalence of psychiatric diagnoses in children with mental retardation (MR) (IQ < or = 70). All children born between 1980 and 1985 (N=30037) in Akershus County, Norway, were screened for possible MR and assessed with either IQ tests or standardized developmental tests. A total of 178 children, 79 with severe mental retardation (SMR) (IQ<50) and 99 with mild mental retardation (MMR) (IQ 50 to 70) were included for further study. Psychiatric symptomatology was assessed as a standard part of the neurodevelopmental examination, which included a semistructured parent interview, a clinical child interview, and retrieval of the charts of previous child psychiatric examinations. Psychiatric diagnoses were classified according to the International Classification of Disease (ICD-10). In total, 65 (37%) of the total population with MR (95% confidence intervals 29 to 44) were registered to have psychiatric diagnoses, the most common being hyperkinesia (n=28) and pervasive developmental disorder (n=15). Psychiatric diagnoses were present in 42% of the population with SMR and 33% of the population with MMR (p=0.4). Of all children found to have a psychiatric diagnosis, approximately one-third had previously been examined by a child psychiatrist and indicated a previously unrecognized need for these services to children with MR.

Adolescent↗
PubMed2000

Cardiac surgery in a girl with trisomy 13.

We describe a profoundly retarded infant girl with multiple anomalies caused by trisomy 13. Due to heart failure, which was resistant to medical treatment, we closed successfully a ventricular septal defect at three months of age. She died at 10 months of age. Despite the short survival, we believe that the patient benefitted significantly from the surgical repair of her cardiac defect.

Abnormalities, Multiple↗
PubMed1999

X linked mental retardation and infantile spasms in a family: new clinical data and linkage to Xp11.4-Xp22.11.

In order to describe the neurological abnormalities and to identify the gene localisation, we re-evaluated a previously reported family with X linked mental retardation (XLMR). Reliable data were obtained for six of the seven affected males, of whom two had had infantile spasms. Profound MR (IQ<20) was found in one and mild MR (IQ 50-70) in five males. No dysmorphic features, except for macrocephaly in one male, were found. Neurological abnormalities included varying degrees of spinocerebellar involvement. Neuroimaging studies showed abnormalities, such as cerebellar atrophy or corpus callosum hypoplasia or both, in three of the six males. Several affected and unaffected subjects suffered from hyperhidrosis, which appeared to segregate independently as an autosomal dominant trait. Genetic linkage analysis localised the XLMR disease gene to Xp11.4-Xp22.11 with a maximum multipoint lod score of 3.57, overlapping the candidate region recently found in two Belgian XLMR-infantile spasm families. Compared to the Belgian patients, the majority of the affected males in this report had a considerably milder phenotype.

Adolescent↗
PubMed1998

Molecular characterization of two deletion events involving Alu-sequences, one novel base substitution and two tentative hotspot mutations in the hypoxanthine phosphoribosyltransferase (HPRT) gene in five patients with Lesch-Nyhan syndrome.

Mutations identified in the hypoxanthine phosphoribosyltransferase (HPRT) gene of patients with Lesch-Nyhan (LN) syndrome are dominated by simple base substitutions. Few hotspot positions have been identified, and only three large genomic rearrangements have been characterized at the molecular level. We have identified one novel mutation, two tentative hot spot mutations, and two deletions by direct sequencing of HPRT cDNA or genomic DNA from fibroblasts or T-lymphocytes from LN patients in five unrelated families. One is a missense mutation caused by a 610C-->T transition of the first base of HPRT exon 9. This mutation has not been described previously in an LN patient. A nonsense mutation caused by a 508C-->T transition at a CpG site in HPRT exon 7 in the second patient and his younger brother is the fifth mutation of this kind among LN patients. Another tentative hotspot mutation in the third patient, a frame shift caused by a G nucleotide insertion in a monotonous repeat of six Gs in HPRT exon 3, has been reported previously in three other LN patients. The fourth patient had a tandem deletion: a 57-bp deletion in an internally repeated Alu-sequence of intron 1 was separated by 14 bp from a 627-bp deletion that included HPRT exon 2 and was flanked by a 4-bp repeat. This complex mutation is probably caused by a combination of homologous recombination and replication slippage. Another large genomic deletion of 2969 bp in the fifth patient extended from one Alu-sequence in the promoter region to another Alu-sequence of intron 1, deleting the whole of HPRT exon 1. The breakpoints were located within two 39-bp homologous sequences, one of which overlapped with a well-conserved 26-bp Alu-core sequence previously suggested as promoting recombination. These results contribute to the establishment of a molecular spectrum of LN mutations, support previous data indicating possible mutational hotspots, and provide evidence for the involvement of Alu-mediated recombination in HPRT deletion mutagenesis.

Alu Elements↗
PubMed1998

Mental retardation in Norway: prevalence and sub-classification in a cohort of 30037 children born between 1980 and 1985.

OBJECTIVES: We wanted to determine the prevalence and subcategories of mental retardation (MR) defined as IQ < or = 70 in Akershus county, which rated by average yearly income, had the second highest socioeconomic status (SES) in Norway. METHODS: The study population consisted of 30 037 children born between 1980 and 1985. Cases were ascertained from multiple sources and psychometrically assessed, predominantly with the Wechsler tests, which were standardized in Norway in 1978. The cases were divided into four groups: profound (IQ < 20), severe (IQ 20-34), moderate (IQ 35-49), and mild (IQ 50-70) MR, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). The median age was 10.8 y. The frequency and degree of parental consanguinity were registered, and the average inbreeding coefficient was calculated. RESULTS: Altogether, 185 had IQ < or = 70, giving a prevalence of MR of 6.2/1000. Prevalences for profound, severe, moderate, and mild MR were 0.8, 0.4, 1.5 and 3.5/1000, respectively. In two, possibly three, cases the parents were second cousins, giving an average inbreeding coefficient of 20-30 x 10(-5). CONCLUSIONS: The low prevalence of MR, particularly mild MR, could partly be explained by high SES, old standardization of IQ-test, and low inbreeding coefficient. The proportion of profound MR was considerably higher than estimated by DSM-IV.

Adolescent↗
PubMed1998

Congenital ptosis and blepharophimosis in a mentally retarded girl: a new case of Ohdo syndrome?

A mentally retarded girl with congenital blepharophimosis, ptosis, hypoplastic teeth and other traits consistent with Ohdo syndrome is reported. Her mother had had surgery for blepharophimosis as a small child, but did not fulfil the other criteria for Ohdo syndrome. The mother had also been abusing alcohol prior to the pregnancy. Differential diagnoses and possible modes of inheritance are discussed.

Abnormalities, Multiple↗
PubMed1997

Encephaloneuropathy with lysosomal zebra bodies and GM2 ganglioside storage.

An 11-year-old girl died of a neuronal storage disorder that clinically was characterized by failure to thrive and muscular hypotonia from birth, with the subsequent evolution of motor neuron disease, epilepsy, and dementia. A wide range of metabolic disorders, including all forms of GM2 gangliosidosis, could be excluded. Electron microscopy demonstrated neuronal zebra body inclusions, and immunohistochemistry demonstrated that GM2 ganglioside was a major constituent of the storage material. We suggest that the patient died of a lysosomal storage disease that is clinically and biochemically different from Tay-Sachs disease, Sandhoff disease, and other GM2 gangliosidoses described previously. This case also further demonstrates that significant accumulation of GM2 ganglioside, which is crucial for dendritic formation, may occur in neuronal storage diseases lacking known defects in ganglioside catabolism.

Child↗
PubMed1997

Macrocephaly, epilepsy, autism, dysmorphic features, and mental retardation in two sisters: a new autosomal recessive syndrome?

We report two sisters with macrocephaly, epilepsy, and severe mental retardation. The first child was a 14 year old girl born at term after a normal pregnancy, with birth weight 3600 g and occipitofrontal circumference (OFC) 36 cm (75th centile). Her head size increased markedly during the first six months of life, and was later stable at 2-3 cm above the 97.5th centile. Her development was characterised by psychomotor delay, epilepsy, and autistic features. Her face appeared mildly dysmorphic with a large forehead, short philtrum, and bushy eyebrows. Her younger sister was also born at term with birth weight 2600 g and OFC 34 cm (25th centile). She also developed postnatal macrocephaly with OFC 2 cm above the 97.5th centile and the same mild dysmorphic facial features as her sister. Her development was also characterised by psychomotor delay, autistic features, and epilepsy. In addition, she suffered from coeliac disease. She died unexpectedly at the age of 5 years, probably from an epileptic attack. Necropsy confirmed megalencephaly but no other pathological changes were found. The clinical features in these two sisters do not fit with any known syndrome and may represent a previously unrecognised autosomal recessive disorder.

Abnormalities, Multiple↗
PubMed1996

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES).

The blepharophimosis-ptosis-epicanthus inversus syndrome is characterized by shortening of the horizontal orbital fissure (blepharophimosis), congenital ptosis and epicanthus inversus. The condition may occur either as an autosomal dominant trait (blepharophimosis-ptosis-epicanthus inversus syndrome types 1 and 2), or sporadically. Blepharophimosis-ptosis-epicanthus inversus syndrome type 1 is associated with female infertility. Mental subnormality may occur, especially in the sporadic cases. Chromosome analysis from a few patients suggests that the genetic defect causing the syndrome is localized to chromosome 3q22.

Blepharophimosis↗
PubMed1995

[Neuronal migration disorders. Radiological and clinical aspects].

Neuronal migration disorders can cause congenital cerebral malformations during the third and fourth months of gestation. They are usually classified as agyria, pachygyria, schizencephaly, polymicrogyria and heterotopic gray matter. The best diagnostic tool for detecting neuronal migration disorders is magnetic resonance imaging (MRI). Frequently, the migration disorders are associated with epilepsy, psychomotor retardation and cerebral palsy, and patients with these symptoms should always be investigated by cerebral MRI. In this article we discuss radiologic and clinical aspects in the case of six persons with different categories of migration disorders.

Abnormalities, Multiple↗
PubMed1995

Atypical methylmalonic aciduria with progressive encephalopathy, microcephaly and cataract in two siblings--a new recessive syndrome?

Two siblings with atypical methylmalonic aciduria and progressive encephalopathy are reported. Initial symptoms were failure to thrive and growth retardation from the first year of life, progressing to severe mental retardation, microcephaly, dystonia, spasticity and cataracts. The amount of methylmalonic acid excreted in the urine was substantially lower than in classical methylmalonic acidemia and was not reduced by vitamin B12 therapy. The activity of methylmalonyl-CoA mutase and the overall assay of propionic acid metabolism in cultured fibroblasts were normal. The primary defect in this probably new autosomal recessive disorder associated with methylmalonic aciduria is currently not known.

Adult↗