Girl with signs of Pelizaeus‐Merzbacher disease heterozygous for a mutation in exon 2 of the proteolipid protein gene

Hodes, M. E.; DeMyer, William; Pratt, Victoria M.; Edwards, Mary K.; Dlouhy, Stephen R.

doi:10.1002/ajmg.1320550402

Cited by 39 publications

(28 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the 36 mutations listed in table I. some clinical data [35] and the mutation was discovered by Trofatteret al [36]. This is one of the largest families (6 generations) described and only I female is affected enough to make the diagnosis [78]. : Early onset occurred in the single male affected and his carrier mother showed gait disorder and personality changes in her mid twenties.…”

Section: Phenotype Of Pmd As Defined By the Cases Showing Mutations Imentioning

confidence: 99%

Genetics of Pelizaeus-Merzbacher Disease

Hodes

Pratt

Dlouhy³

1993

Dev Neurosci

Self Cite

125

View full text Add to dashboard Cite

Pelizaeus-Merzbacher disease (PMD) has been recognized as a clinical entity for more than a century. It has gradually become apparent that the disorder is a dysmyelination, in distinction to demyelinating conditions such as adrenoleukodystrophy. The failure to deposit myelin is due to decreased production of its chief protein, proteolipid protein (PLP). In about 30% of patients with the diagnosis of PMD there is a mutation in the coding portion of the proteolipid protein gene, PLP This gene is located at Xq22 so the disease in these families shows an X-linked pattern of inheritance. The expression of the mutant gene is generally recessive, but some mutations are expressed frequently in females. At least some patients with PMD that do not show mutations in the coding region of PLP demonstrate linkage between the disease and PLP. As additional mutations in PLP are discovered, it is becoming apparent that the nosology of PLP-associated disease is changing. PMD now comprises a spectrum of disorders with similar but not necessarily identical clinical pictures. Some of these disorders may be certain forms of X-linked paraplegia, SPG2. Finally, some diseases that look like PMD may not be X-linked.

show abstract

Section: Phenotype Of Pmd As Defined By the Cases Showing Mutations Imentioning

confidence: 99%

Genetics of Pelizaeus-Merzbacher Disease

Hodes

Pratt

Dlouhy³

1993

Dev Neurosci

Self Cite

125

View full text Add to dashboard Cite

show abstract

“…A few female carriers of point mutations exhibit some of the clinical features of PMD. [10][11][12] There are also several reports of affected females with no identified mutation in the PLP gene; some cases were familial and others were sporadic. It has been suggested that these cases represent an autosomal recessive form of PMD.…”

Section: Introductionmentioning

confidence: 99%

X inactivation phenotype in carriers of Pelizaeus-Merzbacher disease: skewed in carriers of a duplication and random in carriers of point mutations

Woodward¹,

Kirtland²,

Dlouhy

et al. 2000

Eur J Hum Genet

View full text Add to dashboard Cite

Pelizaeus-Merzbacher disease (PMD)is an X-linked recessive disease caused by coding sequence mutations in the PLP gene, sub-microscopic duplications of variable sizes including the PLP gene or very rarely deletions of the PLP gene. We analysed the X inactivation pattern in blood of PMD female carriers with duplications and with point mutations. In the majority of duplication carriers (7/11), the X chromosome bearing the duplication was preferentially inactivated, whereas a random pattern of X inactivation was detected in point mutation carriers (3/3), a deletion carrier (1/1), affected females (4/4) who did not have a recognised mutation and normal control females. However 2/5 non-carrier female relatives of patients with a duplication, had skewed X inactivation. The skewed pattern of inactivation observed in most duplication carriers and not in mutation carriers suggests a) that there is selection against those cells in which the duplicated X chromosome is active and b) other expressed sequences within the duplicated region rather than mutant PLP may be responsible. Since the skewed X inactivation did not segregate with the disease in two families and the pattern of X inactivation was variable among the duplication carriers, the pattern X inactivation is an unsuitable diagnostic tool for female carriers of PMD European Journal of Human Genetics (2000) 8, 449-454.

show abstract

“…This mutation has not been reported before. Other amino acid substitutions in exon 2 are Pro14Leu (Trofatter et al, 1989;Hodes et al, 1995) and Thr42lle Pratt et al5 .1995); a single base (A or G at the third position of codon 55, Gin) synonymous polymorphism was described by Osaka et al (1995). 31 The segregation of the Phe Val mutation in our family (Fig.…”

mentioning

confidence: 57%