Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome

• Published in: Journal of medical genetics Vol. 41; no. 8; pp. 609 - 614
• Main Authors: Plasilova, M, Chattopadhyay, C, Pal, P, Schaub, N A, Buechner, S A, Mueller, Hj, Miny, P, Ghosh, A, Heinimann, K
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.08.2004; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Abdomen; Adolescent; Aging, Premature - genetics; autosomal recessive inheritance; Biological and medical sciences; Biopsy; Child; Child, Preschool; Deoxyribonucleic acid; Disease; DNA; DNA Mutational Analysis - methods; Families & family life; Female; General aspects. Genetic counseling; Genes; Genes, Recessive - genetics; Genetic Carrier Screening; Genetic disorders; Genetic Linkage - genetics; Genetic testing; Genomes; HGPS; Humans; Hutchinson-Gilford progeria syndrome; Hypotheses; India; lamin A/C gene; Lamin Type A - genetics; Letter to JMG; LMNA; Loss of Heterozygosity - genetics; MAD; Male; mandibuloacral dysplasia; Medical genetics; Medical sciences; Mutation; Mutation, Missense - genetics; Pedigree; Progeria - genetics; Progeria - pathology; Senescence; Stem cells; Dwarfism; Human; Skin disease; Missense mutation; Gene; Autosomal character; Progeria; Recessive character; Genetics; Homozygosity; Syndrome; Genetic disease
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2004.019661

[...]to B-type lamins, which are ubiquitously expressed in all cell types at all developmental stages, A-type lamins are absent in the cells of the early embryo, embryonic stem cells, stem cells of the immune and haematopoietic systems as well as in cells of the neuroendocrine system (reviewed in Goldman et al 8 and Mounkes et al 9 ). Besides HGPS, germline mutations in LMNA have been shown to cause seven phenotypically different disorders, inherited in an autosomal dominant and/or recessive manner. 4, 5, 10 Considering the tissue(s) affected, they can be grouped into those involving mainly (i) striated and cardiac muscle, (ii) peripheral nerves, and (iii) white adipose tissue and bones. 9 Together with HGPS, two of them belong to the so-called progeroid syndromes: an atypical form of Werner syndrome (WRN; MIM 277700) and mandibuloacral dysplasia (MAD; MIM 248370). [...]this is the first report of a consanguineous HGPS family providing molecular evidence for autosomal recessive inheritance of HGPS. [...]in addition to Emery-Dreifuss muscular dystrophy (EDMD2, MIM181350; EDMD3, MIM604929), HGPS represents the second laminopathy where germline mutations in the LMNA gene can cause disease in both a dominant and recessive mode of inheritance.