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.
Madej-Pilarczyk
Agnieszka
A
Neuromuscular Unit, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
Rosińska-Borkowska
Danuta
D
Rekawek
Joanna
J
Marchel
Michał
M
Szaluś
Ewa
E
Jabłońska
Stefania
S
Hausmanowa-Petrusewicz
Irena
I
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