LETTER TO JMG

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

M Plasilova^1,*, C Chattopadhyay^2,3,*, P Pal^2,4, N A Schaub⁵, S A Buechner⁵, Hj Mueller¹, P Miny¹, A Ghosh², K Heinimann¹

¹ Research Group Human Genetics, Division of Medical Genetics, University Children’s Hospital and Department of Research, 4005 Basel, Switzerland
² Institute of Child Health, 11 Dr Biresh Guha Street, Calcutta 700017, India
³ Calcutta Project Foundation, University of Basel, 4031 Basel, Switzerland
⁴ S.B. Devi Charity Home, 6 Gulu Ostagar Lane, Calcutta 700006, India
⁵ Department of Dermatology, University Clinics, 4031 Basel, Switzerland

Correspondence to:
Correspondence to:
Dr Ghosh
Institute of Child Health, 11 Dr Biresh Guha Street, Calcutta 700017, India; apurbaghosh@yahoo.com
Dr Heinimann
Research Group Human Genetics, Division of Medical Genetics, University Children’s Hospital, Roemergasse 8, 4005 Basel, Switzerland; karl.heinimann@unibas.ch

Received 12 March 2004

Accepted 12 March 2004

Abbreviations: HGPS, Hutchinson-Gilford progeria syndrome; LMNA, lamin A/C gene; MAD, mandibuloacral dysplasia

Keywords: autosomal recessive inheritance; Hutchinson-Gilford progeria syndrome; LMNA

The first 150 words of the full text of this article appear below.

Hutchinson-Gilford progeria syndrome (HGPS; MIM 176670) is an extremely rare genetic disorder displaying features reminiscent of premature senescence.^1,2 Typically, affected children appear normal at birth, but begin to develop characteristic symptoms within the first years of life such as failure to thrive, alopecia, lipodystrophy, and scleroderma-like skin changes. Though the first HGPS cases were described more than 100 years ago,^1,3 its extreme rarity (1:4–8 000 000) and mostly sporadic occurrence made it difficult to identify the underlying genetic cause. By means of homozygosity mapping as well as candidate gene analysis, two research groups recently reported that heterozygous, recurrent de novo point mutations in the lamin A/C gene (LMNA; MIM 150330), a component of the filamentous meshwork of the nuclear lamina, caused HGPS.^4,5

LMNA encodes two A-type lamins, lamin A and C, which are the result of alternative splicing and share the first 566 amino acids.^6,7 Together with B-type . . . [Full text of this article]

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