Contributions
Abstract: PB1836
Type: Publication Only
Background
Severe congenital neutropenia (SCN) is characterized by profound neutropenia and a predisposition to life-threatining bacterial infections. Autosomal dominant, autosomal recessive, X-linked and sporadic SCN forms have all been described. Mutations in several genes including ELANE, GFI1, HAX-1, G6PC3 and WAS are responsible for SCN. CSF3R mutations are extremely rare and usually somatic.
Aims
Here we describe an SCN case having a novel homozygous CSF3R mutation.
Methods
A-5-month-old boy was referred to our department because of neutropenia. There was a history of hospitalization because of cervical lymphadenitis and neck abscess at the age of 3 months. The parents were consanguineous. Physical examination was normal (no dysmorphic findings such as leukoplaki, nail dystrophy, brown ridging on the neck, thumb abnormalities, etc.were present). Laboratory tests revealed a severe neutropenia (300/mm3). Lymphocyte count, serum immunoglobulin levels and peripheral lymhocyte subset analysis were all normal. Viral infection markers were negative. Neutropenia persistedat the level of 200-400/mm3. In the following8 weekperiod, the neutrophile count was monitored twice weekly. All neutrophile counts were below 500/mm3. A bone marrow examination revealed normocellularity and maturation arrest of granulocytic series at the level of band form. Cytogenetic studies were normal. The patient did not respond to G-CSF therapy and the neutropenia persisted. The patient is now 21-month-old and has experienced several febrile neutropenia episodes. Bone marrow transplantation has been planned. Unfortunately to date no HLA matched donor within the family has been found.
Results
Molecular genetic analysis for ELA-2, HAX-1, G6PC3, SBDS were normal. However, in the CSF3R genea novel homozygous p.V224D (c.671 (T>A)) mutation was detected. Using in silico analysis this novel mutation was found to be pathogenic. A functional analysis has been planned.
Conclusion
CSF3R mutations in SCN cases are usually somatic or de novo and inherited form is extremely rare (Triot A, et al 2014). It has been considered that the SCN case described here will expand the mutation spectrum of GCSF3R gene and help to make phenotype-genotype correlations.
Rerefence
1. Triot A, Jarvinen PM, Arostegui JI, Murugan D, Kohistani N, Dapena Diaz JL, et al. Inherited biallelic CSF3R mutations in severe congenital neutropenia. Blood. 2014 Jun 12;123(24):3811-7.
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): Childhood, Mutation, neutropenia
Abstract: PB1836
Type: Publication Only
Background
Severe congenital neutropenia (SCN) is characterized by profound neutropenia and a predisposition to life-threatining bacterial infections. Autosomal dominant, autosomal recessive, X-linked and sporadic SCN forms have all been described. Mutations in several genes including ELANE, GFI1, HAX-1, G6PC3 and WAS are responsible for SCN. CSF3R mutations are extremely rare and usually somatic.
Aims
Here we describe an SCN case having a novel homozygous CSF3R mutation.
Methods
A-5-month-old boy was referred to our department because of neutropenia. There was a history of hospitalization because of cervical lymphadenitis and neck abscess at the age of 3 months. The parents were consanguineous. Physical examination was normal (no dysmorphic findings such as leukoplaki, nail dystrophy, brown ridging on the neck, thumb abnormalities, etc.were present). Laboratory tests revealed a severe neutropenia (300/mm3). Lymphocyte count, serum immunoglobulin levels and peripheral lymhocyte subset analysis were all normal. Viral infection markers were negative. Neutropenia persistedat the level of 200-400/mm3. In the following8 weekperiod, the neutrophile count was monitored twice weekly. All neutrophile counts were below 500/mm3. A bone marrow examination revealed normocellularity and maturation arrest of granulocytic series at the level of band form. Cytogenetic studies were normal. The patient did not respond to G-CSF therapy and the neutropenia persisted. The patient is now 21-month-old and has experienced several febrile neutropenia episodes. Bone marrow transplantation has been planned. Unfortunately to date no HLA matched donor within the family has been found.
Results
Molecular genetic analysis for ELA-2, HAX-1, G6PC3, SBDS were normal. However, in the CSF3R genea novel homozygous p.V224D (c.671 (T>A)) mutation was detected. Using in silico analysis this novel mutation was found to be pathogenic. A functional analysis has been planned.
Conclusion
CSF3R mutations in SCN cases are usually somatic or de novo and inherited form is extremely rare (Triot A, et al 2014). It has been considered that the SCN case described here will expand the mutation spectrum of GCSF3R gene and help to make phenotype-genotype correlations.
Rerefence
1. Triot A, Jarvinen PM, Arostegui JI, Murugan D, Kohistani N, Dapena Diaz JL, et al. Inherited biallelic CSF3R mutations in severe congenital neutropenia. Blood. 2014 Jun 12;123(24):3811-7.
Session topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Keyword(s): Childhood, Mutation, neutropenia