Genetic and clinical characteristics of pediatric patients with familial hemophagocytic lymphohistiocytosis
BACKGROUND: Our study was designed to investigate the frequencies and distributions of familial hemophagocytic lymphohistiocytosis (FHL) associated genes in Saudi patients.
METHODS: FHL associated gene screening was performed on 87 Saudi patients who were diagnosed with hemophagocytic lymphohistiocytosis (HLH) between 1995 and 2014. The clinical and biochemical profiles were also retrospectively captured and analyzed.
RESULTS: Homozygous mutations and mono-allelic variants were identified in 66 (75.9%) and 3 (3.5%) of the study participants, respectively. STXBP2 was the most frequently mutated gene (36% of patients) and mutations in STXBP2 and STX11 accounted for 58% of all FHL cases and demonstrated a specific geographical pattern. Patients in the FHL group presented at a significantly younger age than those belonging to the unknown-genetics group (median, 3.9 vs. 9.4 mo; P=0.005). The presenting clinical features were similar among the various genetic groups and the 5-year overall survival (OS) was 55.4% with a 5.6 year median follow-up. Patients with PRF1 mutations had a significantly poorer 5-year OS (21.4%, P =0.008) and patients undergoing hematopoietic stem cell transplant (72.4%) had a significantly better 5-year OS (66.5% vs. 0%, P =0.001).
CONCLUSION: Our study revealed the predominance of the STXBP2 mutations in Saudi patients with FHL. A genetic diagnosis was possible in 80% of the cohort and our data showed improved survival in FHL patients who underwent hematopoietic stem cell transplant.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:56 |
|---|---|
| Enthalten in: |
Blood research - 56(2021), 2 vom: 30. Juni, Seite 86-101 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ahmari, Ali Al [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Genetic mutation |
|---|
| Anmerkungen: |
Date Revised 24.04.2022 published: Print Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.5045/br.2021.2020308 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM326318321 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM326318321 | ||
| 003 | DE-627 | ||
| 005 | 20231225194332.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.5045/br.2021.2020308 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1087.xml |
| 035 | |a (DE-627)NLM326318321 | ||
| 035 | |a (NLM)34083498 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ahmari, Ali Al |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genetic and clinical characteristics of pediatric patients with familial hemophagocytic lymphohistiocytosis |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 24.04.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a BACKGROUND: Our study was designed to investigate the frequencies and distributions of familial hemophagocytic lymphohistiocytosis (FHL) associated genes in Saudi patients | ||
| 520 | |a METHODS: FHL associated gene screening was performed on 87 Saudi patients who were diagnosed with hemophagocytic lymphohistiocytosis (HLH) between 1995 and 2014. The clinical and biochemical profiles were also retrospectively captured and analyzed | ||
| 520 | |a RESULTS: Homozygous mutations and mono-allelic variants were identified in 66 (75.9%) and 3 (3.5%) of the study participants, respectively. STXBP2 was the most frequently mutated gene (36% of patients) and mutations in STXBP2 and STX11 accounted for 58% of all FHL cases and demonstrated a specific geographical pattern. Patients in the FHL group presented at a significantly younger age than those belonging to the unknown-genetics group (median, 3.9 vs. 9.4 mo; P=0.005). The presenting clinical features were similar among the various genetic groups and the 5-year overall survival (OS) was 55.4% with a 5.6 year median follow-up. Patients with PRF1 mutations had a significantly poorer 5-year OS (21.4%, P =0.008) and patients undergoing hematopoietic stem cell transplant (72.4%) had a significantly better 5-year OS (66.5% vs. 0%, P =0.001) | ||
| 520 | |a CONCLUSION: Our study revealed the predominance of the STXBP2 mutations in Saudi patients with FHL. A genetic diagnosis was possible in 80% of the cohort and our data showed improved survival in FHL patients who underwent hematopoietic stem cell transplant | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Genetic mutation | |
| 650 | 4 | |a Hemophagocytic lympho-histiocytosis | |
| 650 | 4 | |a PRF1 | |
| 650 | 4 | |a STX11 | |
| 650 | 4 | |a STXBP2 | |
| 650 | 4 | |a UNC13D | |
| 700 | 1 | |a Alsmadi, Osama |e verfasserin |4 aut | |
| 700 | 1 | |a Sheereen, Atia |e verfasserin |4 aut | |
| 700 | 1 | |a Elamin, Tanziel |e verfasserin |4 aut | |
| 700 | 1 | |a Jabr, Amal |e verfasserin |4 aut | |
| 700 | 1 | |a El-Baik, Lina |e verfasserin |4 aut | |
| 700 | 1 | |a Alhissi, Safa |e verfasserin |4 aut | |
| 700 | 1 | |a Saud, Bandar Al |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Awwami, Moheeb |e verfasserin |4 aut | |
| 700 | 1 | |a Fawaz, Ibrahim Al |e verfasserin |4 aut | |
| 700 | 1 | |a Ayas, Mouhab |e verfasserin |4 aut | |
| 700 | 1 | |a Siddiqui, Khawar |e verfasserin |4 aut | |
| 700 | 1 | |a Hawwari, Abbas |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Blood research |d 2013 |g 56(2021), 2 vom: 30. Juni, Seite 86-101 |w (DE-627)NLM226712613 |x 2287-979X |7 nnns |
| 773 | 1 | 8 | |g volume:56 |g year:2021 |g number:2 |g day:30 |g month:06 |g pages:86-101 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.5045/br.2021.2020308 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 56 |j 2021 |e 2 |b 30 |c 06 |h 86-101 | ||