Journal of Blood Disorders & Transfusion

Novel molecular changes in Saudi patients with familial hemophagocytic lymphohistiocytosis

7^th World Hematologists Congress

May 08-09, 2017 Barcelona, Spain

Ali Al Ahmari, Osama Alsmadi, Atia Sheereen, Lina Eibaik1, Tanziel Elamin, Amal Jabr, Bandar Al Saud, Moheeb Al-Awwami, Ibrahim Al-Fawaz, Mouhab Ayas, Khawar Siddiqui, Mohammad Viqaruddin and Abbas Hawwari

King Faisal Specialist Hospital and Research Centre, Saudi Arabia
Alfaisal University, Saudi Arabia

Posters & Accepted Abstracts: J Blood Disord Transfus

Abstract:

Background: Familial hemophagocytic lymphohistiocytosis (FHL) in different ethnicities has been described in the literature, but this is the first report from Saudi Arabia describing the novel mutations present in FHL genes. Methods: 87 patients diagnosed with FHL from January 1995 to December 2014 at King Faisal Specialist Hospital and Research Centre was screened for HLH-associated genes. Their clinical and biochemical profiles were retrospectively captured. DNA from peripheral blood were used for mutation detection in various HLH genes- PRF1, UNC13D, STX11, STXBP2, LYST, rab27A, SH2D1A and XIAP by PCR-sequencing method. We report herein those with novel molecular changes. Results: Biallelic mutations were identified in 66 patients (75.86%) in whom 18 (27.3%) patients were found to harbor 10 novel mutations distributed among five HLH-associated genes. STXBP2 mutations were identified in the majority of patients (38%). All mutations were found to be damaging and disease. 10 patients with UNC13D had four novel mutations, two of which resulted in a stop codon. The most prevalent mutation is c.3048_3049insC (p.E1017RfsX8) was found in six patients. One patient had a novel missense mutation (c.862 T>C, p.W288R) in STXBP2 gene. Another STX11 mutation (601_602ins C, p. Q140Pfs*46) was found in one patient. Four novel mutations were found in seven patients in other genes (LYST and rab27A). The novel molecular changes and their associated clinical characteristics were shown. Parent consanguinity and history of siblings with HLH were observed in 77% and 26% of patients, respectively. Furthermore, a tribal and geographical pattern was clearly found in patients harboring STX11, STXBP2 and Unc13D mutations. STXBP2 mutations are the most prevalent among Saudi FHL patients. Conclusion: In more than a quarter of mutations in Saudi patients with FHL are novel. Furthermore, in quarter of our patients, no molecular defects were identified. This indicates that there are still more mutations to be discovered and also the possibilities of deep intronic mutations and other genetic aberrations cannot be definitely excluded. A high rate of consanguineous marriages and endogamy is seen in Saudi Arabians�??, and is present in large groups. A tribal and geographical pattern was clearly observed. Though the treatment is standardized for HLH, the impact of ethnicity and race on the severity and outcome may warrant further investigation.

Biography :

Email: cenzensberger@googlemail.com