Unusual Clinical and Magnetic Resonance Imaging Findings in a Family With Proteolipid Protein Gene Mutation

Battini, Roberta; Bianchi, Maria Cristina; Boespflug‐Tanguy, Odile; Tosetti, Michela; Bonanni, Paolo; Canapicchi, R.; Cioni, Giovanni

doi:10.1001/archneur.60.2.268

Cited by 11 publications

(4 citation statements)

References 10 publications

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“…Other genetic disorders with X‐linked inheritance, like fragile X, FG, Opitz syndromes and some disorders of cortical development, which can be symptomatic in carrier mothers, were soon excluded on clinical grounds, laboratory investigation and brain neuroimaging. X‐linked PLP gene was tested in patient 1 because of pyramidal signs and slight white matter abnormalities [Battini et al, 2003].…”

Section: Discussionmentioning

confidence: 99%

Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X‐linked mental retardation in two unrelated Dutch families

Mancini

Catsman‐Berrevoets

Coo

et al. 2004

American J of Med Genetics Pt A

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Four Dutch male patients, two brothers from unrelated families were referred for investigation of psychomotor and severe language/speech delay. All four patients showed growth deficiency over the years. Facial features and poor body habitus were quite similar in the patients and in their mothers. Brain MRI showed nonspecific periventricular white matter lesions. In all the patients neuropsychological tests revealed moderate mental retardation, attention deficit and hyperactivity with impulsivity, a semantic-pragmatic language disorder, and oral dyspraxia. This specific cognitive profile is different from other children with mental retardation syndromes and seems to be unique. Excretion of creatine to creatinine ratio in urine of the four boys was increased compared to controls and their creatine uptake in fibroblasts was deficient. In the two brothers from the first pedigree, DNA sequence analysis revealed a novel mutation in the splice donor site in intron 10 (IVS10 + 5G>C, c.1495 + 5G>C) of the SLC6A8 gene leading to skipping of exon 10. In the other sib pair a novel missense mutation (c. 1361C>T; p.Pro544Leu) was found. These are the first families reported, in which the clinical suspicion of a creatine transporter disorder was raised on clinical grounds, before a brain 1H-MRS suggested the diagnosis. Screening of apparently X-linked mental retarded patients with this somatic and behavioral phenotype by the biochemical assay of creatine to creatinine ratio in the urine or DNA sequence analysis of SLC6A8 is worthwhile even when 1H-MRS is not available.

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Section: Discussionmentioning

confidence: 99%

Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X‐linked mental retardation in two unrelated Dutch families

Mancini

Catsman‐Berrevoets

Coo

et al. 2004

American J of Med Genetics Pt A

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“…Adult patients with SPG2, as well as clinically asymptomatic obligate carrier mothers of males with classical Pelizaeus-Merzbacher disease, have been described with non-specific periventricular and subependymal white matter changes on MRI, and cystic changes in the basal ganglia (Fig. 2J and K;Battini et al, 2003;Warshawsky et al, 2005;Hurst et al, 2006). A young female presenting with subacute gait disturbance and periventricular white matter lesions was recently described with biallelic pathogenic mutations in SPG11 ( Fig.…”

Section: Hereditary Spastic Paraplegiasmentioning

confidence: 99%

Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis

Weisfeld-Adams

Sand

Honce

et al. 2015

Brain

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Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient's 'multiple sclerosis-like' phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis.

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“…223,224 A high prevalence of WMHs is also found in 22q11-deletion syndrome frequently associated with psychosis, 225 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which is caused by mutations in the NOTCH3 gene on chromosome 19 and frequently associated with depression, and other less common genetic conditions. [226][227][228][229] Nongenetic factors are associated with WMHs as well; [230][231][232][233][234][235][236][237][238] for example, Moore et al 239 reported a correlation between WMH and season of birth in a group of patients with BD. Thus, it appears that WMHs are not specific to BD and their usefulness as an endophenotype remains to be established.…”

Section: Basal Gangliamentioning

confidence: 99%

The phenotypes of bipolar disorder: relevance for genetic investigations

2005

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The search for susceptibility genes for bipolar disorder (BD) depends on appropriate definitions of the phenotype. In this paper, we review data on diagnosis and clinical features of BD that could be used in genetic studies to better characterize patients or to define homogeneous subgroups. Clinical symptoms, long-term course, comorbid conditions, and response to prophylactic treatment may define groups associated with more or less specific loci. One such group is characterized by symptoms of psychosis and linkage to 13q and 22q. A second group includes mainly bipolar II patients with comorbid panic disorder, rapid mood switching, and evidence of chromosome 18 linkage. A third group comprises typical BD with an episodic course and favourable response to lithium prophylaxis. Reproducibility of cognitive deficits across studies raises the possibility of using cognitive profiles as endophenotypes of BD, with deficits in verbal explicit memory and executive function commonly reported. Brain imaging provides a more ambiguous data set consistent with heterogeneity of the illness. Keywords: bipolar disorder; genetics; endophenotype; neurocognitive function; brain imaging Bipolar disorder (BD) has a genetic basis with heritability of at least 80%. 1 A number of studies have attempted to map the susceptibility loci giving evidence of linkage in multiple genomic regions. In particular, findings in 4p, 4q, 8q, 10p, 12q24, 13q, 18p, 18q, 21q, and 22q have been supported by more than one study. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] However, these studies have not identified any specific genes, and a recent metaanalysis of available genome scans showed no regions with a conclusive evidence of linkage. 20 The relatively slow progress of gene-mapping efforts is often explained by the 'complex' nature of the illness and of the genotype-phenotype relation. The complexity most likely includes heterogeneity, interactions of multiple loci, incomplete penetrance, as well as phenotypes resulting from environmental effects-either alone or in interaction with the genetic predisposition. The goal of psychiatric genetic research is identification of (heritable) variations in DNA sequence or function that influence behaviour or give rise to mental illness. By definition, in complex (multifactorial) traits, this link is not unique and specific. That is, a particular change in gene sequence does not necessarily lead to a specific behaviour, and similar behaviours (symptoms) may be due to distinct (sets of) genes. Moreover, we must consider the possibility that the path between the genotype and behaviour is not unidirectional. Emerging examples point not only to general effects of environment, for instance stress, on behaviour, but also to specific behaviours influencing gene function that can be transmitted onto the next generation. 21 No single method is considered clearly superior in identifying susceptibility genes for complex traits such as BD. Most researchers agree that a combination of strategies is most lik...

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Unusual Clinical and Magnetic Resonance Imaging Findings in a Family With Proteolipid Protein Gene Mutation

Abstract: The unusual genetic, magnetic resonance imaging, and clinical findings of this family confirm the wide variability of PLP-related disorders.

Cited by 11 publications

References 10 publications

Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X‐linked mental retardation in two unrelated Dutch families

Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X‐linked mental retardation in two unrelated Dutch families

Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis

The phenotypes of bipolar disorder: relevance for genetic investigations

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