A severe form of Noonan syndrome and autosomal dominant café-au-lait spots: evidence for different genetic origins

Nyström, Anna-MajaUppsala universitet,Institutionen för genetik och patologi (författare)

A severe form of Noonan syndrome and autosomal dominant café-au-lait spots : evidence for different genetic origins

De två (2) sista författarna delar sistaförfattarskapet.
Aim: The clinical overlap among Noonan syndrome (NS), cardio-facio-cutaneous (CFC), LEOPARD and Costello syndromes as well as Neurofibromatosis type 1 is extensive, which complicates the process of diagnosis. Further genotype–phenotype correlations are required to facilitate future diagnosis of these patients. Therefore, investigations of the genetic cause of a severe phenotype in a patient with NS and the presence of multiple café-au-lait spots (CAL) spots in the patient and four members of the family were performed. Methods: Mutation analyses of candidate genes, PTPN11, NF1, SPRED1 and SPRED2, associated with these syndromes, were conducted using DNA sequencing. Results: A previously identified de novo mutation, PTPN11 F285L and an inherited NF1 R1809C substitution in the index patient were found. However, neither PTPN11 F285L, NF1 R1809C, SPRED1 nor SPRED2 segregated with CAL spots in the family. The results indicate that the familial CAL spots trait in this family is caused by a mutation in another gene, distinct from previous genes associated with CAL spots in these syndromes. Conclusion: We suggest that the atypical severe symptoms in the index patient may be caused by an additive effect on the F285L mutation in PTPN11 by another mutation, for example the NF1 R1809C or alternatively, the not yet identified gene mutation associated with CAL spots in this family.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
Café-au-lait spots
Mutation
NF1
Noonan syndrome
PTPN11
Molecular medicine (genetics and pathology)
Molekylär medicin (genetik och patologi)
Clinical Genetics
Klinisk genetik

Ekvall, SaraUppsala universitet,Medicinsk genetik(Swepub:uu)sarek497 (författare)
Strömberg, BoUppsala universitet,Pediatrik,Barnneurologisk forskning/Ahlsten(Swepub:uu)bostromb (författare)
Holmström, GerdUppsala universitet,Oftalmiatrik(Swepub:uu)gerdholm (författare)
Thuresson, Ann-CharlotteUppsala universitet,Medicinsk genetik(Swepub:uu)anncthur (författare)
Annerén, GöranUppsala universitet,Medicinsk genetik(Swepub:uu)goraanne (författare)
Bondeson, Marie-LouiseUppsala universitet,Medicinsk genetik(Swepub:uu)malobond (författare)
Uppsala universitetInstitutionen för genetik och patologi (creator_code:org_t)

Av författaren/redakt...: Nyström, Anna-Ma ...; Ekvall, Sara; Strömberg, Bo; Holmström, Gerd; Thuresson, Ann-C ...; Annerén, Göran; visa fler...; Bondeson, Marie- ...; visa färre...

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