SDHB and SDHD mutations in hereditary para ganglioma/pheochromocytoma (pgl-pheo) síndrome.

SANSÓ G; VIEITES A; LEVIN G; DAHIA PL; BARONTINI M

Mar del Plata, Argentina

Congreso; XIX Reunión anual de la Sociedad Latinoamericana de Investigación Pediátrica; 2007

Sociedad Latinoamericana de Endocrinologïa Pediátrca

Recently has been established that in about 25 % of cases, pheo and functional pgl are inherited and caused by mutations in one of four genes responsible for: MEN 2, VHL, NF1 and pgl-pheo syndrome. The last is related to mutations in succinato dehidrogenase. Germ-line mutations in SDHD have been identified in multigenerational families and are the predominant causes of head and neck pgl. SDHB mutations have been identified in head, neck and abdominal pgl with malignant behavior. The aim of this study was to establish the mutations in the SDHD and SDHB gene in a group of patients with pgl-pheo syndrome. Seven patients (12-35y) affected with pgl and/or malignant pheo were studied. The study was extended to 37 family members. To characterize SDHD mutations we screened the four exons of this gene using PCR followed by direct sequencing and HpyCH4III enzyme digestion. To characterize SDHB mutations PCR-based SSCP strategy followed by direct sequencing was performed. Two patients with neck pgl presented SDHD deletions; in one of them who also had pheo, a dinucleotide deletion c.341-2ATdel was present. The deletion was detected in 14/27 family members belonging to four generations. Five showed clinical evidence of the disease, while the remaining nine were unaffected carriers. A clear pattern of maternal imprinting was present in these kindred, in agreement with other data on SDHD inheritance. A nucleotide deletion (c.57-Gdel) was found in the other patient with apparently sporadic disease. 3/5 patients with SDHB mutations had abdominal or thoracic pgl (two of them malignant); one had adrenal pheo (malignant) and the remaining a malignant head and neck pgl. Three SDHB mutations were identified: R217G, S198R, g300-304 CCTCAdel. 5/10 family members were unaffected carriers. Our date show that in patients with clinical features of pgl-pheo syndrome is mandatory SDHB or SDHD genes testing to establish the etiological diagnosis, clinical management and genetic counseling.