Collect

Blood sample in an EDTA (purple-top) tube.

Storage/Transport Temperature

Room Temp

Performed

Monday-Friday 9:00am - 4:00pm

Volume Required

3-5 ml

Minimum Required

1.5 mL

Phlebotomy Draw

Yes

Performed

Monday-Friday 9:00am - 4:00pm

Methodology

Twenty-two genes known to be associated with inherited neutropenia are analyzed using Next Generation Sequence (NGS) technology. All coding exons of the 22 genes and 20 base pairs of 5' and 3' flanking intronic sequences are analyzed. All known intronic mutations of these genes are also evaluated. Pathogenic/likely pathogenic variants detected by NGS are confirmed by Sanger sequencing.
The panel also evaluates gross copy number variations of these genes by analyzing NGS data. Pathogenic/likely pathogenic CNVs detected by NGS are confirmed by MLPA and/or ddPCR. Certain genes or exons may not be evaluated for gross copy number variations, such as genes with no known gross deletion/duplication mutations, or genes or exons with pseudogenes or highly homologous sequences in the genome.

Reported

42 days

Synonyms

  • Congenital neutropenia, Barth syndrome, Cartilage-hair hypoplasia, CHH, Chediak Hiashi syndrome, Cohen syndrome, G6PC3 deficiency, Glycogen Storage Disease 1, Glycogen Storage Disease 1B, GSD1, GSD1b, Hermansky-Pudlak syndrome, Shwachman-Diamond syndrome, Wiscott-Aldrich syndrome, Griscelli syndrome, Poikiloderma
  • INEUP
  • AP3B1, CSF3R, CXCR4, ELANE, G6PC3, GATA1, GATA2, GFI1, HAX1, LAMTOR2, LYST, RAB27A, RAC2, RMRP, SBDS, SLC37A4, TAZ, USB1, VPS13B, VPS45, WAS, WIPF1

LIS Mnemonic

INEUP

Performed By

Division of Genomic Diagnostics

Available STAT

No

Clinical Features

The Inherited Neutropenia Panel is a next generation sequencing panel designed to identify underlying genetic variants associated with inherited neutropenia of childhood. Inherited neutropenia of childhood can be associated with a variety of genetic syndromes and can be caused by pathogenic variants in at least 22 genes. Frequent symptoms associated with inherited neutropenia include recurrent infections, recurrent fevers, inflammation of the skin and gums, osteopenia, and leukemia or myelodysplastic syndrome. Due to variety of syndromes associated with inherited neutropenia and the phenotypic overlap between these conditions, establishing a genetic diagnosis is essential for accurately tailoring individualized treatment approaches and helping to differentiate inherited neutropenia from immune or neoplastic neutropenia causes.

Detection Rate

The diagnostic yield for comprehensive NGS panels is not yet well-established, and depends on the panel's gene content and the patient's clinical features. Estimated detection rates are provided for pathogenic variants in the genes on this panel that can be identified by gene sequencing for probands meeting the clinical diagnostic criteria for specific disorders:

Congenital Neutropenia: ~38-80% associated with ELANE pathogenic variants [PMID: 20301705]
Barth syndrome: >95% [PMID: 25299040]
Cartilage-hair hypoplasia: >95% [PMID: 17189938]
Chediak-Higashi syndrome: ~90% [PMID: 20301751]
Cohen syndrome: >95% [PMID: 21330571, 19006247]
G6PC3 deficiency: ~43% [PMID: 25879134]
Glycogen Storage Disease Type 1b: >95% [PMID: 20301489]
Hermansky-Pudlak syndrome: ~11% [PMID: 20301464]
Shwachman-Diamond syndrome: >90% [PMID: 20301722]
Wiskott-Aldrich syndrome: >95% [PMID: 20301357]

Molecular Testing Notes

Conditions associated with inherited neutropenia can be inherited in an autosomal dominant, autosomal recessive, or x-linked manner. The Inherited Neutropenia Panel includes the following 22 genes: AP3B1, CSF3R, CXCR4, ELANE, G6PC3, GATA1, GATA2, GFI1, HAX1, LAMTOR2, LYST, RAB27A, RAC2, RMRP, SBDS, SLC37A4, TAZ, USB1, VPS13B, VPS45, WAS, and WIPF1.

CPT Codes

81406x3, 81408, 81479
Collection

Collect

Blood sample in an EDTA (purple-top) tube.

Storage/Transport Temperature

Room Temp

Performed

Monday-Friday 9:00am - 4:00pm

Volume Required

3-5 ml

Minimum Required

1.5 mL

Phlebotomy Draw

Yes
Ordering

Performed

Monday-Friday 9:00am - 4:00pm

Methodology

Twenty-two genes known to be associated with inherited neutropenia are analyzed using Next Generation Sequence (NGS) technology. All coding exons of the 22 genes and 20 base pairs of 5' and 3' flanking intronic sequences are analyzed. All known intronic mutations of these genes are also evaluated. Pathogenic/likely pathogenic variants detected by NGS are confirmed by Sanger sequencing.
The panel also evaluates gross copy number variations of these genes by analyzing NGS data. Pathogenic/likely pathogenic CNVs detected by NGS are confirmed by MLPA and/or ddPCR. Certain genes or exons may not be evaluated for gross copy number variations, such as genes with no known gross deletion/duplication mutations, or genes or exons with pseudogenes or highly homologous sequences in the genome.

Reported

42 days

Synonyms

  • Congenital neutropenia, Barth syndrome, Cartilage-hair hypoplasia, CHH, Chediak Hiashi syndrome, Cohen syndrome, G6PC3 deficiency, Glycogen Storage Disease 1, Glycogen Storage Disease 1B, GSD1, GSD1b, Hermansky-Pudlak syndrome, Shwachman-Diamond syndrome, Wiscott-Aldrich syndrome, Griscelli syndrome, Poikiloderma
  • INEUP
  • AP3B1, CSF3R, CXCR4, ELANE, G6PC3, GATA1, GATA2, GFI1, HAX1, LAMTOR2, LYST, RAB27A, RAC2, RMRP, SBDS, SLC37A4, TAZ, USB1, VPS13B, VPS45, WAS, WIPF1

LIS Mnemonic

INEUP

Performed By

Division of Genomic Diagnostics

Available STAT

No

Clinical Features

The Inherited Neutropenia Panel is a next generation sequencing panel designed to identify underlying genetic variants associated with inherited neutropenia of childhood. Inherited neutropenia of childhood can be associated with a variety of genetic syndromes and can be caused by pathogenic variants in at least 22 genes. Frequent symptoms associated with inherited neutropenia include recurrent infections, recurrent fevers, inflammation of the skin and gums, osteopenia, and leukemia or myelodysplastic syndrome. Due to variety of syndromes associated with inherited neutropenia and the phenotypic overlap between these conditions, establishing a genetic diagnosis is essential for accurately tailoring individualized treatment approaches and helping to differentiate inherited neutropenia from immune or neoplastic neutropenia causes.

Detection Rate

The diagnostic yield for comprehensive NGS panels is not yet well-established, and depends on the panel's gene content and the patient's clinical features. Estimated detection rates are provided for pathogenic variants in the genes on this panel that can be identified by gene sequencing for probands meeting the clinical diagnostic criteria for specific disorders:

Congenital Neutropenia: ~38-80% associated with ELANE pathogenic variants [PMID: 20301705]
Barth syndrome: >95% [PMID: 25299040]
Cartilage-hair hypoplasia: >95% [PMID: 17189938]
Chediak-Higashi syndrome: ~90% [PMID: 20301751]
Cohen syndrome: >95% [PMID: 21330571, 19006247]
G6PC3 deficiency: ~43% [PMID: 25879134]
Glycogen Storage Disease Type 1b: >95% [PMID: 20301489]
Hermansky-Pudlak syndrome: ~11% [PMID: 20301464]
Shwachman-Diamond syndrome: >90% [PMID: 20301722]
Wiskott-Aldrich syndrome: >95% [PMID: 20301357]

Molecular Testing Notes

Conditions associated with inherited neutropenia can be inherited in an autosomal dominant, autosomal recessive, or x-linked manner. The Inherited Neutropenia Panel includes the following 22 genes: AP3B1, CSF3R, CXCR4, ELANE, G6PC3, GATA1, GATA2, GFI1, HAX1, LAMTOR2, LYST, RAB27A, RAC2, RMRP, SBDS, SLC37A4, TAZ, USB1, VPS13B, VPS45, WAS, and WIPF1.
Result Interpretation
Administrative

CPT Codes

81406x3, 81408, 81479