Fine mapping of Noonan/cardio-facio cutaneous syndrome in a large family

Abstract

Noonan syndrome (NS) is an autosomal dominant condition with facial dysmorphy, congenital cardiac defects and short stature. A gene for NS has previously been linked to a 14 cM region in 12q24. 2 We performed linkage analysis in a four generation Belgian family with NS in some individuals and cardio-facio-cutaneous (CFC) syndrome in others. Clinical data and linkage data in this family indicate that NS and CFC syndrome result from a variable expression of the same genetic defect. We report a maximum lod score of 4.43 at zero recombination for marker D12S84 in 12q24. A crossover in this pedigree narrows the candidate gene region for NS to a 5 cM interval between markers D12S84 and D12S1341.

PTPN11 mutation in a large family with Noonan syndrome and dizygous twinning

“…3,9 At this moment however one cannot conclude that these individuals had classical CFC syndrome. Further PTPN11 mutation analysis in a large group of patients with classical CFC syndrome will show if there is a relation between CFC and PTPN11.…”

“…3,9 Essentially we sampled 10 affected individuals, seven unaffected relatives and three spouses (Figure 1). Most affected individuals have a typical Noonan syndrome phenotype with the typical facial dysmorphy and pale grey-blue eyes.…”

“…Two large families were used to map the syndrome to a 5 cM interval between markers D12S84 and D12S1341 on chromosome 12q24. 2,3 Recently missense mutations in PTPN11 (MIM 176876) have been found in 9 NS families and four individual cases, corresponding to 50% of the cases analysed. Genetic heterogeneity has also been shown by lack of linkage to 12q24 of several smaller nuclear families.…”

“…In this family some individuals present with NS and features suggestive of CFC 8 and others with NS features only. 3,9 Subjects, material and methods…”

Síndrome de Noonan: relato de caso

“…O gene responsável por esta síndrome foi mapeado no braço longo do cromossomo 12 (3)(4) , porém algumas famílias não apresentam alterações nessa região, indicando heterogenicidade genética nessa desordem (3) .…”