Germinal mosaicism in Noonan syndrome: A family with two affected siblings of normal parents.
Noonan syndrome (NS; OMIM 163950) is an autosomal dominant disorder with variable clinical expression and genetic heterogeneity. Clinical manifestations include characteristic facial features, short stature, and cardiac anomalies. Mutations in protein-tyrosine phosphatase, non-receptor-type 11 (PTPN11), encoding SHP-2, account for about half of NS patients. We report on a Moroccan family with two children with NS and apparently unaffected parents. The molecular studies showed the heterozygous mutation c.922A>G of PTPN11 gene in the two affected sibs. Neither the parents, nor the oldest brother carries this mutation in hematologic cells. The mutation was also absent in buccal epithelial cells and fingernails of both parents. We believe this is the first report of germ cell mosaicism in NS and suggest an empirical risk for recurrence of that is less than 1%.
Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco. sihamgen@yahoo.fr
Siham Chafai
SC
Elalaoui
Lilia
L
Kraoua
Céline
C
Liger
Ilham
I
Ratbi
Hélène
H
Cavé
Abdelaziz
A
Sefiani
D000328:Adult; D002675:Child, Preschool; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D009634:Noonan Syndrome / Q000201:enzymology / Q000235:genetics*; D010290:Parents; D010375:Pedigree; D011247:Pregnancy; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics; D035781:Siblings
C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11