Journal Article Missense mutations are frequent in the gene for X-chromosomal adrenoleukodystrophy (ALD) Get access Sigrid Fuchs, Sigrid Fuchs * Institut für Humangenetik, Medizinische Universität, Ratzeburger Allee 160, D-23538 LübeckGermany * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Claude Olivier Sarde, Claude Olivier Sarde 1LGME du CNRS, INSERM Unité 184, Faculté de Médicine and CHRU, F-67085 StrasbourgFrance Search for other works by this author on: Oxford Academic PubMed Google Scholar Heike Wedemann, Heike Wedemann Institut für Humangenetik, Medizinische Universität, Ratzeburger Allee 160, D-23538 LübeckGermany Search for other works by this author on: Oxford Academic PubMed Google Scholar Eberhard Schwinger, Eberhard Schwinger Institut für Humangenetik, Medizinische Universität, Ratzeburger Allee 160, D-23538 LübeckGermany Search for other works by this author on: Oxford Academic PubMed Google Scholar Jean Louis Mandel, Jean Louis Mandel 1LGME du CNRS, INSERM Unité 184, Faculté de Médicine and CHRU, F-67085 StrasbourgFrance Search for other works by this author on: Oxford Academic PubMed Google Scholar Andreas Gal Andreas Gal Institut für Humangenetik, Medizinische Universität, Ratzeburger Allee 160, D-23538 LübeckGermany Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 3, Issue 10, October 1994, Pages 1903–1905, https://doi.org/10.1093/hmg/3.10.1903 Published: 01 October 1994 Article history Received: 20 June 1994 Revision received: 19 July 1994 Accepted: 19 July 1994 Published: 01 October 1994
Abstract We report on monozygotic twins with different clinical phenotypes of X‐linked adrenoleukodystrophy. At the age of 10 years both boys were neurologically asymptomatic. The first cranial magnetic resonance examination showed normal findings in the first twin and parietooccipital demyelination in the second. The latter developed behavioral problems 9 months later, followed by visual impairment and gait ataxia. His cranial magnetic resonance image at the age of 11 years showed progressive demyelination. In contrast, neurological status and magnetic resonance images remained normal in the first twin. The same point mutation in exon 8 of the adrenoleukodystrophy gene (C2203T) was detected in both boys. All genotype examinations were consistent with the diagnosis of monozygotic twins, suggesting that some nongenetic factors may be important for different adrenoleukodystrophy phenotypes.
Genetic studies were performed in four German families with autosomal dominant myoclonus-dystonia syndrome. Mutations in the D2 dopamine receptor gene, which have been implicated in this disorder, were excluded in all four families by linkage analysis and direct sequencing. All four families supported linkage to the second reported locus on chromosome 7q21 with a combined maximum multipoint lod score of 5.99. The observation of key recombinations in one family refined the disease locus to a 7.2 cM region flanked by the markers D7S652 and D7S2480. Ann Neurol 2001;49:121–124
Journal Article Heterozygous 'null allele' mutation in the human peripherin/RDS gene Get access M. Meins, M. Meins Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Grüning, G. Grüning Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Blankenagel, A. Blankenagel 1Augenklinik der Universitat, D-69120 HeideibergGermany Search for other works by this author on: Oxford Academic PubMed Google Scholar H. Krastel, H. Krastel 1Augenklinik der Universitat, D-69120 HeideibergGermany Search for other works by this author on: Oxford Academic PubMed Google Scholar B. Reck, B. Reck 1Augenklinik der Universitat, D-69120 HeideibergGermany Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Fuchs, S. Fuchs Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Schwinger, E. Schwinger Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Gal A. Gal * *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 2, Issue 12, December 1993, Pages 2181–2182, https://doi.org/10.1093/hmg/2.12.2181 Published: 01 December 1993 Article history Received: 02 August 1993 Revision received: 16 September 1993 Accepted: 16 September 1993 Published: 01 December 1993
Hallermann-Streiff syndrome (HSS) is a rare inherited disorder characterized by malformations of the cranium and facial bones, congenital cataracts, microphthalmia, skin atrophy, hypotrichosis, proportionate short stature, teeth abnormalities, and a typical facial appearance with prominent forehead, small pointed nose, and micrognathia. The genetic cause of this developmental disorder is presently unknown. Here we describe 8 new patients with a phenotype of HSS. Individuals with HSS present with clinical features overlapping with some progeroid syndromes that belong to the laminopathies, such as Hutchinson-Gilford progeria syndrome (HGPS) and mandibuloacral dysplasia (MAD). HGPS is caused by de novo point mutations in the LMNA gene, coding for the nuclear lamina proteins lamin A and C. MAD with type A and B lipodystrophy are recessive disorders resulting from mutations in LMNA and ZMPSTE24, respectively. ZMPSTE24 in addition to ICMT encode proteins involved in posttranslational processing of lamin A. We hypothesized that HSS is an allelic disorder to HGPS and MAD. As the nuclear shape is often irregular in patients with LMNA mutations, we first analyzed the nuclear morphology in skin fibroblasts of patients with HSS, but could not identify any abnormality. Sequencing of the genes LMNA, ZMPSTE24 and ICMT in the 8 patients with HSS revealed the heterozygous missense mutation c.1930C>T (p.R644C) in LMNA in 1 female. Extreme phenotypic diversity and low penetrance have been associated with the p.R644C mutation. In ZMPSTE24 and ICMT, no pathogenic sequence change was detected in patients with HSS. Together, we found no evidence that HSS is another laminopathy.
