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Test Code LAB3799 ImmuneSeq Autoimmune Lymphoproliferative Syndrome (ALPS) DNA Sequencing

Clinical System Name

ImmuneSeq Autoimmune Lymphoproliferative Syndrome (ALPS) DNA Sequencing

Description

Clinical Features

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of immune regulation characterized by disruption of lymphocyte homeostasis through altered lymphocyte apoptosis (Bride and Teachey, 2017). The clinical manifestations of ALPS include non-malignant lymphoproliferation such as lymphadenopathy or hepatosplenomegaly, autoimmune disease that typically involves blood cells, and increased risk for both Hodgkin and non-Hodgkin lymphoma (Bleesing et al., 2017). The characteristic laboratory abnormalities associated with ALPS include (1) an expansion of T cells that express the alpha/beta T-cell receptor but lack both CD4 and CD8 (double negative T cells) in peripheral blood and tissue samples (Shah et al., 2014) and (2) increased levels of ALPS-specific biomarkers such as soluble IL-10, IL-18, FasL, and vitamin B12 in plasma/serum (Bowen et al., 2012).

 

The Seattle Children’s Hospital Molecular Genetics Laboratory offers testing of 21 genes for the Autoimmune Lymphoproliferative Syndrome (ALPS) panel. Reported genes are listed below.

 

Prevalence

ALPS is a rare disorder and its true prevalence is unknown (Shah et al., 2014). Nearly 500 patients with ALPS have been reported worldwide (Bleesing et al., 2017).

 

Inheritance

Most cases of ALPS-FAS and ALPS-CASP10, and some cases of ALPS-FASLG are inherited in an autosomal dominant manner. Most cases of ALPS-FASLG and severe ALPS are inherited in an autosomal recessive manner. ALPS-sFAS can occur as a result of somatic mosaicism. ALPS-FAS is the most common and best-characterized subtype (Bleesing et al., 2017).

 

ImmuneSeq Autoimmune Lymphoproliferative Syndrome (ALPS) DNA Sequencing Panel: BACH2, CASP10, CASP8, CD70, CTLA4, FADD, FAS, FASLG, ITCH, ITK, JAK1, MAGT1, OTULIN, PIK3CD, PIK3R1, PRKCD, RELA, STAT3, TET2, TNFRSF6B, TPP2

 

Additional testing options - we offer the following additional options for custom Immunodeficiency testing:

 

Please contact LabGC@seattlechildrens.org if you would like to order reflexive testing after the original testing report has been issued.

Sample Requirements

Note: For patients who have had a whole blood transfusion, wait 10 days post transfusion to draw for genetic testing. No wait time is necessary for blood or saliva collection if the patient received leuko-reduced red cells or plasma.

 

Specimen: Whole blood

Container(s): Lavender/EDTA

Preferred Vol: 3 mL

Minimum Vol: 1 mL

Note: Heparin samples (Green tops) are unacceptable.

 

Specimen: Saliva collected using Oragene Dx OGD-575/675 collection kit.

Container: Oragene Dx OGD-575/675 collection kit

IMPORTANT NOTE: Manufacturer instructions must be followed. The Oragene Dx OGD575/675 kit is not for children under 6 months. Contact the lab directly for more information or to obtain a kit - 206-987-2617

 

Specimen: Extracted DNA (MUST specify source on requisition)

Preferred: 10µg

Minimum: 5µg

Note: Isolation of nucleic acids for clinical testing must be performed in a CLIA-certified
laboratory or a laboratory meeting equivalent requirements as determined by the CAP
and/or the CMS. DNA concentration minimum 50 µg/mL; 260/280 ratio 1.70-2.00.

 

Specimen: Skin biopsy (MUST specify source on requisition)

Preferred: 2-4 mm punch biopsy of skin collected under sterile conditions refrigerated with 1-3 mL of tissue transport medium.

Note:  DO NOT use formaldehyde, formalin, alcohol, or 5% dextrose. Do not freeze.

 

Specify tissue source and site on requisition.

Processing Instructions

 

Specimen Type Description

Temperature

 Storage instructions
Whole blood EDTA or ACD tube Refrigerate Molecular Genetics box in CPA refrigerator #2
Extracted DNA DNA aliquot tube Refrigerate Molecular Genetics box in CPA refrigerator #2
Saliva OGD-575/675 kit Room Temp Place in CPA Cytogenetics room temp box with requisition
Skin biopsy with 1-3 mL of tissue transport medium Refrigerate Molecular Genetics box in CPA refrigerator #2

Off-site collection: Refrigerate blood samples until ready to ship.  Transport blood, saliva, or DNA at room temperature via overnight shipping.

Stability

Stability

Specimen Type Temperature Time
Whole blood, extracted DNA RT 3-5 d
Whole blood, extracted DNA 2 - 8 C

7 d

Saliva, extracted from ORAgene Dx OGD-575/675

 Room temperature or refrigerated up to 2 weeks
Extracted DNA -20 C or -70 C  years
Skin biopsy Refrigerated (in medium) 3 days

Note: Whole blood samples > 7days may be submitted to be assessed by our lab for acceptability for testing.

Availability

STAT Performed TAT
Contact lab Monday - Friday 4-6 weeks

Performing Laboratory

Seattle Children's Laboratory

Department

Department:  Molecular Genetics Laboratory

Phone: 206-987-3872

Lab Client Services: 206-987-2617

Lab Genetic Counselor: LabGC@seattlechildrens.org

CPT Codes

81479

Methodology

Method: Next Generation Sequencing technology using an Illumina NextSeq instrument. Target region includes coding exons and a minimum of 10 bp of flanking intron boundaries of the genes tested. Target enrichment performed using a custom Integrated DNA Technologies (IDT) Exome Hyb Panel v2. 

 

Average coverage ~150x.

 

Limitations:

This testing is performed on an exome backbone with analysis restricted to the panel genes. This method can detect single nucleotide variants (SNVs), small deletions, small insertions, and copy number variants in the regions targeted. Some regions cannot be efficiently captured due to sequence homology or sequence properties. This method will not detect large insertions and deletions, complex indels, structural variants (e.g. inversions, translocations), short tandem repeats, or other complex variants. Variants located outside of targeted regions will not be detected.

 

Based on validation studies, the bioinformatics pipeline showed precision and detection >99% for SNVs in regions with coverage greater than 20x and high mapping quality. Sensitivity for CNVs involving multiple genes is >99% and sensitivity for intragenic CNVs is >90%. Mosaic sequence variants present at <25% allele frequency may not be reliably detected, and detection sensitivity is dependent on the nature of the variant. The sensitivity of detection of mosaic copy number variants has not been evaluated.

 

Reported Gene Lists

The Seattle Children's Hospital Molecular Laboratory offers different immune disorder panels based on clinical presentation with additional testing options. Reported gene lists are below and detailed descriptions are available. All panels include copy number analysis and may identify mosaicism.

 

ImmuneSeq Panel

Genes

Severe combined immunodeficiency (SCID) – 149 genes

ACD, ADA, AK2*, ARPC1B, ATM, BACH2, B2M, BCL10, BCL11B, BLM, CARD11, CARMIL2, CCBE1, CD247, CD27, CD28, CD3D, CD3E, CD3G, CD40, CD40LG, CD8A, CDCA7, CHD7, CIITA, CORO1A*, CRACR2A, CTC1, CTPS1, CXCR4, DCLRE1B, DCLRE1C*, DIAPH1, DKC1, DNMT3B, DOCK2, DOCK8, EPG5, ERBIN, ERCC6L2, EXTL3, FADD, FAT4, FCHO1, FOXI3, FOXN1, GINS1, HELLS, ICOS, ICOSLG, IKBKB, IKBKG*, IKZF1, IKZF3, IL21, IL21R, IL2RG, IL6R, IL6ST, IL7, IL7R, ITK, JAK3, KDM6A, KMT2D, LAT, LCK, LIG1, LIG4, LRBA, MAGT1, MALT1, MAP3K14, MCM4, MCM10, MSN, MTHFD1, MYSM1, NBN, NFE2L2, NFKBIA, NHEJ1, NHP2, NOP10, NSMCE3, OTULIN, ORAI1, PARN, PAX1, PGM3, PIK3CD, PIK3R1, PMS2, PNP, POLA1, POLD1, POLD2, POLE, POLE2, PRKDC, PTPRC, RAC2, RAG1, RAG2, RBCK1, REL, RELA, RELB, RFX5, RFXANK, RFXAP, RHOH, RMRP, RNF168, RNF31, RNU4ATAC, RTEL1, SEMA3E, SH2D1A, SKIC2/SKIV2L, SKIC3/TTC37, SLC46A1, SMARCAL1, SP110, SPINK5, STAT3, STAT5B, STIM1, STK4, STN1, TAP1, TAP2, TAPBP, TBX1, TCN2, TERC, TERT, TFRC, TINF2, TNFRSF4, TP63, TPP2, TRAC, TTC7A, WAS, WIPF1, ZAP70, ZBTB24, ZNF341

Autoimmune Lymphoproliferative Syndrome (ALPS) – 21 genes

BACH2, CASP10, CASP8, CD70, CTLA4, FADD, FAS, FASLG, ITCH, ITK, JAK1, MAGT1, OTULIN, PIK3CD, PIK3R1, PRKCD, RELA, STAT3, TET2, TNFRSF6B,TPP2

Familial Hemophagocytic Lymphohistiocytosis (FHLH) – 33 genes

AP3B1, BTK, CEBPE, CD27, CD40LG, CD70, CTPS1, FAAP24, ITK, LRBA, LYST, MAGT1, MCM4, MVK, NFKB1, NLRC4, PIK3CD, PIK3R1, PNP, PRF1, PRKCD, RAB27A, RAC2, RASGRP1, RHOG, SH2D1A, SLC7A7, STK4, STX11, STXBP2, UNC13D**, WAS, XIAP

Very Early Onset Inflammatory Bowel Disease (VEO-IBD)/Early Onset Enteropathy – 114 genes

ADA, ADAM17, AICDA, ALG6, ALPI, ANKZF1, AP3B1, AP3D1, ARPC1B, BACH2, BTK, CARD11, CARD8, CARMIL2, CASP8, CD3G, CD40, CD40LG, CD55, COL7A1, CTLA4, CYBA, CYBB, CYBC1, CYP27A1, DCLRE1C*, DEF6, DGAT1, DKC1, DOCK8, DUOX2, EGFR, EPCAM, FCHO1, FERMT1, FOXP3, G6PC3, GUCY2C, HPS1*, HPS3, HPS4, HPS5, HPS6, HRAS, ICOS, IKBKG*, IL10, IL10RA, IL10RB, IL21, IL2RA, IL2RB, IL2RG, ITCH, ITGB2, JAK1, LCT, LIG4, LIPA, LRBA, MALT1, MEFV, MVK, MYO5B, NCF1*, NCF2, NCF4, NEUROG3, NFAT5, NFKB1, NFKBIA, NLRC4, NLRP12, NOD2, NPC1, PIK3CD, PIK3R1, PLCG2, PLVAP, POLA1, PTEN, RAC2, RAG1, RAG2, RIPK1, RTEL1, SAR1B, SH2D1A, SI, SKIC2/SKIV2L, SKIC3/TTC37, SLC26A3, SLC37A4, SLC9A3, SLCO2A1, SPINT2, STAT1, STAT3, STAT5B, STIM1, STX3, STXBP2, TGFB1, TGFBR1, TGFBR2, TNFAIP3, TRIM22, TTC7A, UNC45A, WAS, XIAP, ZAP70, ZBTB24, ZNF341

Expanded – 738 genes

ABCB7, ABCG5, ABCG8, ACD, ACP5, ACTB*, ACTG1, ACTN1, ADA, ADA2, ADAM17, ADAMTS13, ADAMTS3, ADAR, ADIPOQ, ADIPOR1, ADIPOR2, AICDA, AIRE, AK2*, ALAS2, ALG6, ALPI, AMN, ANGPT1, ANKRD11, ANKRD26, ANKZF1, AP1S3, AP3B1, AP3D1, APOL1, ARHGEF1, ARPC1B, ASAH1, ATAD3A, ATG4A, ATM, ATP11C, ATP6AP1, ATR, ATRX, B2M, BACH1, BACH2, BANK1, BCL10, BCL11B, BCO1, BLK, BLM, BLNK, BLOC1S3, BLOC1S6, BRAF, BRCA1, BRCA2, BRIP1, BTK, C1QA, C1QB, C1QBP, C1QC, C1R, C1S, C2, C2orf69, C3, C3AR1, C4BPA, C4BPB, C5, C5AR1, C5AR2, C6, C7, C8A, C8B, C8G, C9, CARD11, CARD14, CARD8, CARD9, CARMIL2, CASP10, CASP8, CBL, CCBE1, CCDC103, CCDC39, CCDC40, CCDC65, CCNK, CCNO, CD19, CD247, CD27, CD28, CD3D, CD3E, CD3G, CD40, CD40LG, CD46, CD55, CD59, CD70, CD79A, CD79B, CD81, CD8A, CD93, CDAN1, CDC42*, CDCA7, CDK9, CDKN2A, CEBPA, CEBPE, CENPF, CFAP298, CFAP300, CFB, CFD, CFH*, CFI, CFP, CFTR*, CHD7, CHEK2*, CHUK, CIB1, CIITA, CLCN7, CLEC7A, CLPB, CLU, COG6, COL7A1, COLEC11, COPA, COPG1, CORO1A*, CPT2, CR2, CRACR2A, CREBBP, CRP, CSF2RA*, CSF2RB, CSF3R, CTC1, CTLA4, CTNNBL1, CTPS1, CTSC, CXCR2, CXCR4, CYBA, CYBB, CYBC1, CYCS*, CYP27A1, DBR1, DCLRE1B, DCLRE1C*, DDX11*, DDX41, DEF6, DGAT1, DGKE, DHFR*, DIAPH1, DKC1, DNAAF1, DNAAF11/LRRC6, DNAAF2, DNAAF3, DNAAF4, DNAAF5, DNAAF6/PIH1D3, DNAH1, DNAH11, DNAH5, DNAH8, DNAH9, DNAI1, DNAI2, DNAJB13, DNAJC21, DNALI1, DNASE1L3, DNASE2, DNMT3B, DOCK11, DOCK2, DOCK8, DRC1, DSG1, DTNBP1, DUOX2, EFL1, EGFR, EIF2AK3, ELANE, ELF4, EPCAM, EPG5, EPO, ERBIN, ERCC2, ERCC3, ERCC4, ERCC6L2, ETV6, EXTL3, F12, FAAP100, FAAP24, FADD, FANCA, FANCB, FANCC, FANCD2*, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FAS, FASLG, FAT4, FCGR2A, FCGR2B*, FCGR3A, FCGR3B, FCHO1, FCN1, FCN2, FCN3, FERMT1, FERMT3, FLG, FLI1, FLNA, FNIP1, FOXI3, FOXN1, FOXP3, FPR1, FYB1, G6PC1/G6PC, G6PC3, G6PD, GAS2L2, GAS8, GATA1, GATA2, GBA1*, GFI1, GFI1B, GINS1, GLRX5, GNE, GP1BA, GP1BB, GP9, GTF2E2, GTF2H5, GUCY2C, HAVCR2, HAX1, HCK, HELLS, HMOX1, HNRNPK, HOXA11, HPS1*, HPS3, HPS4, HPS5, HPS6, HRAS, HSPA9, HTRA2, HYDIN*, HYOU1, ICOS, ICOSLG, IFIH1, IFNAR1, IFNAR2, IFNG, IFNGR1, IFNGR2, IGHM, IGKC, IGLL1, IKBKB, IKBKG*, IKZF1, IKZF2, IKZF3, IKZF5, IL10, IL10RA, IL10RB, IL12B, IL12RB1, IL12RB2, IL17F, IL17RA, IL17RC, IL18BP, IL18RAP, IL1RN, IL21, IL21R, IL23R, IL2RA, IL2RB, IL2RG, IL36RN, IL6R, IL6ST, IL7, IL7R, INO80, INSYN1, INVS, IRAK1, IRAK4, IRF2, IRF2BP2, IRF3, IRF4, IRF5, IRF7, IRF8, IRF9, ISG15, ITCH, ITGA2B, ITGAM, ITGB2, ITK, ITPKB, JAGN1, JAK1, JAK2, JAK3, KAT6A, KCNN4, KDM1A, KDM6A, KIF23, KLF1, KMT2A, KMT2D, KRAS, LAG3, LAMTOR2, LAT, LCK, LCP2, LCT, LIG1, LIG4, LIPA, LPIN2, LRBA, LRRC56, LRRC8A, LSM11, LYN, LYST, LZTR1, MAD2L2, MAGT1, MALT1, MAN2B1, MAN2B2, MANBA, MAP1LC3B2, MAP2K1, MAP2K2, MAP3K14, MAPK8, MASP1, MASP2, MASTL, MAT2A, MBL2, MCIDAS, MCM10, MCM4, MECOM, MEFV, MLH1, MLPH, MOGS, MPIG6B, MPL, MPLKIP, MPO, MRAS, MRE11, MRTFA, MS4A1, MSH2, MSH6, MSN, MTHFD1, MVK, MYD88, MYH9, MYO5A, MYO5B, MYSM1, NAF1, NBAS, NBEAL2, NBN, NCF1*, NCF2, NCF4, NCKAP1L, NCSTN, NEUROG3, NF1*, NFAT5, NFE2L2, NFIL3, NFKB1, NFKB2, NFKBIA, NHEJ1, NHP2, NLRC4, NLRP1*, NLRP12, NLRP3, NME8, NOD2, NOP10, NOS2, NPC1, NRAS, NSMCE3, NUP214, OAS1, ODAD1/CCDC114, ODAD2/ARMC4*, ODAD3/CCDC151, ODAD4/TTC25, OFD1, ORAI1, OSTM1, OTUD6B, OTULIN, PALB2, PARN, PAX1, PAX5, PDCD1, PEPD, PGM3, PIGA, PIK3CD, PIK3CG, PIK3R1, PLCG2, PLEKHM1*, PLG, PLVAP, PMM2*, PMS2, PNP, POLA1, POLD1, POLD2, POLE, POLE2, POLR3A, POLR3C, POLR3F, POMP, POT1, POU2AF1, PRF1, PRG4, PRKACG, PRKCD, PRKDC, PSEN1, PSENEN, PSMA3, PSMB10, PSMB4, PSMB8, PSMB9, PSMG2, PSTPIP1, PTEN, PTPN11, PTPRC, PTX3, PUS1, RAB27A, RAC2, RAD50, RAD51, RAD51C, RAF1, RAG1, RAG2, RANBP2, RAP1A, RAP1B, RASA2, RASGRP1, RBCK1, RBM8A*, RC3H1, RECQL4, REL, RELA, RELB, RFWD3, RFX5, RFXANK, RFXAP, RHOG, RHOH, RIGI/DDX58, RIPK1, RIT1, RMRP, RNASEH2A, RNASEH2B, RNASEH2C, RNF113A, RNF168, RNF31, RNU4ATAC, RORC, RPGR*, RPL10, RPL11, RPL15, RPL18, RPL19, RPL26, RPL27, RPL31, RPL35A, RPL36, RPL5, RPS10, RPS19*, RPS24, RPS26, RPS27A, RPS28, RPS29, RPS7, RPS9, RPSA, RRAS, RSPH1, RSPH3, RSPH4A, RSPH9, RTEL1, RUNX1, SAMD9, SAMD9L, SAMHD1, SAR1B, SASH3, SBDS*, SBF2, SCO2, SEC23B, SEC61A1, SEMA3E, SERPING1, SH2B3, SH2D1A, SH3BP2, SH3KBP1, SHOC2, SI, SIAE, SKIC2/SKIV2L, SKIC3/TTC37, SLC10A2, SLC19A2, SLC25A38, SLC26A3, SLC29A3, SLC35A1, SLC35C1, SLC37A4, SLC39A4, SLC39A7, SLC46A1, SLC5A1, SLC7A7, SLC9A3, SLCO2A1, SLFN14, SLX4, SMARCAL1, SMARCD2, SNORA31, SNX10, SOCS1, SOCS4, SOS1, SOS2, SP110, SPAG1, SPI1, SPINK5, SPINT2, SPPL2A, SRC, SRP54, SRP72, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, STIM1, STING1/TMEM173, STK36, STK4, STN1, STX11, STX3, STXBP2, STXBP3, SYK, TAFAZZIN/TAZ, TAOK2, TAP1, TAP2, TAPBP, TBK1, TBX1, TBX21, TBXAS1, TCF3, TCIRG1, TCN2, TERC, TERF2, TERF2IP, TERT, TET2, TFRC, TGFB1, TGFBR1, TGFBR2, THBD, THPO, THRA, THRB, TICAM1, TIMM50, TINF2, TIRAP, TLR3, TLR7, TLR8, TMC6, TMC8, TNFAIP3, TNFRSF11A, TNFRSF13B, TNFRSF13C, TNFRSF1A, TNFRSF4, TNFRSF6B, TNFRSF9, TNFSF11, TNFSF12, TNFSF13, TNFSF4, TOM1, TONSL, TOP2B, TP53, TP63, TPP2, TRAC, TRADD, TRAF3, TRAF3IP2, TREX1, TRIM22, TRNT1, TSR2, TTC7A, TUBB1, TYK2, UBA1, UBE2T, UNC119, UNC13D**, UNC45A, UNC93B1, UNG, USB1, USP18*, VAV1, VPS13B, VPS45, VSIG4, VTN, WAS, WDR1, WIPF1, WRAP53, XIAP, XRCC2, ZAP70, ZBTB24, ZCCHC8, ZMYND10, ZNF341, ZNFX1

Primary Ciliary Dyskinesia (PCD)  – 56 genes

CCDC103, CCDC39, CCDC40, CCDC65, CCNO, CFAP221, CFAP298, CFAP300, CFAP54, CFAP57, CFAP74, CFTR*, CLXN, DNAAF1, DNAAF11, DNAAF2, DNAAF3, DNAAF4, DNAAF5, DNAAF6, DNAH1, DNAH11, DNAH5, DNAH9, DNAI1, DNAI2, DNAJB13, DNAL1, DRC1, FOXJ1, GAS2L2, GAS8, HYDIN*, IFT74, LRRC56, MCIDAS, NEK10, NME5, NME8, ODAD1, ODAD2*, ODAD3, ODAD4, OFD1, RPGR*, RSPH1, RSPH3, RSPH4A, RSPH9, SPAG1, SPEF2, STK36, TP73, TTC12, TUBB4B, ZMYND10

*Gene with known pseudogenes that may impact ability to detect variants or have additional limitations resulting in low coverage.

**The UNC13D 253 kb inversion described in the literature (Meeths et al., 2011) is outside of the target region and will not be detected by this assay.

Reference Range

Interpretive report will be provided. Variants are classified using the ACMG/AMP guidelines (PMID: 25741868). Variants are that are considered neutral, risk alleles, or associated with carrier status for recessive disorders are not routinely reported.

Clinical Utility

While individually rare, immune disorders are a significant health burden. This is not a complete list, but genetic testing may be considered in individuals when the clinical differential diagnosis includes:

  • Dyskeratosis congenita
  • SCID
  • Bloom syndrome
  • CHARGE syndrome
  • Bone Marrow Failure
  • Roifman-Chitayat syndrome
  • SHORT syndrome
  • IMAGE-I syndrome
  • RIDDLE syndrome
  • Trichohepatoenteric syndrome
  • Wiskott-Aldrich syndrome

References

  • Bride K and Teachey D. Autoimmune lymphoproliferative syndrome: more than a FAScinating disease. F1000Res. 2017 Nov 1;6:1928, PMID: 29123652.
  • Bleesing JJH, et al. Autoimmune Lymphoproliferative Syndrome. 2006 Sep 14 [updated 2017 Aug 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301287.
  • Shah S, et al. Autoimmune lymphoproliferative syndrome: an update and review of the literature. Curr Allergy Asthma Rep. 2014 Sep;14(9):462, PMID: 25086580.
  • Bowen RA, et al. Elevated vitamin B₁₂ levels in autoimmune lymphoproliferative syndrome attributable to elevated haptocorrin in lymphocytes. Clin Biochem. 2012 Apr;45(6):490-2, PMID: 22306884.
  • Meeths M, et al. Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) caused by deep intronic mutation and inversion in UNC13D. Blood. 2011 Nov 24;118(22):5783-93, PMID: 21931115.

Requisition

Molecular Genetics