Progeroid syndrome with scleroderma-like skin changes associated with homozygous R435C LMNA mutation.
Hutchinson-Gilford progeria is a rare genetic disorder resulting from mutations in the LMNA gene encoding lamin A/C. In addition to the classical phenotype usually caused by the 1824C>T mutation of LMNA, a number of atypical progeroid syndromes have been described. They have some distinct features, such as skeletal deformities or scleroderma-like skin changes. The underlying defect is usually a homozygous mutation of LMNA, or a combined defect of LMNA and another gene, for example, ZMPSTE-24. We present a 2-year-old girl born to consanguineous parents affected by progeroid syndrome with scleroderma-like skin changes. Genetic analysis revealed the homozygous LMNA mutation 1303C>T (R435C). The same heterozygous mutation was found in the patient's parents and 11 other family members. The progeroid syndrome in our patient shares the signs of two laminopathies: progeria and restrictive dermatopathy. Two other children in the family died at the age of 2 due to a disease similar to that in the proposita. On the basis of the family pedigree we presume that these children probably had the same homozygous LMNA mutation. Scleroderma-like skin changes in infants, associated with growth retardation and dysmorphic features, suggest premature aging syndrome, requiring genetic testing and counseling of asymptomatic carriers of LMNA mutations.
Neuromuscular Unit, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
Agnieszka
A
Madej-Pilarczyk
Danuta
D
Rosińska-Borkowska
Joanna
J
Rekawek
Michał
M
Marchel
Ewa
E
Szaluś
Stefania
S
Jabłońska
Irena
I
Hausmanowa-Petrusewicz
D000015:Abnormalities, Multiple / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D034904:Lamin Type A / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D011371:Progeria / Q000150:complications* / Q000235:genetics*; D012594:Scleroderma, Localized / Q000150:complications* / Q000235:genetics; D012867:Skin / Q000473:pathology*; D013577:Syndrome
C494847:LMNA protein, human; D034904:Lamin Type A