Combined immunodeficiency
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Immunodeficiency Main Page |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ali Akram, M.B.B.S.[2], Anmol Pitliya, M.B.B.S. M.D.[3] Anum Gull M.B.B.S.[4]
Overview
Classification
| Combined Immunodeficiency Diseases with associated or syndromic features | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital thromocytopenia | DNA Repair Defects | Immuno-osseous dysplasias | Thymic Defects with additional congenital anomalies | Hyper-IgE syndromes(HIES) | Dyskeratosis congenita (DKC) | Defects of Vitamin B12 and Folate metabolism | Anhidrotic Ectodermodysplasia with ID | Others | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Wiskott Aldrich Syndrome | Ataxia telangiectasia | Cartilage Hair Hypoplasia | DiDeorge Syndrome | Job Syndrome | Dyskeratosis congenita | Transcobalmin 2 deficiency | NEMO deficiency | Purine nucleoside phosphorylase deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| XL thrombocytopenia | Nijmegen breakage Syndrome | Schimke Syndrome | TBX1 deficiency | Comel Netherton Syndrome | COATS plus syndrome | Deficiency causing hereditary folate malabsorption | EDA-ID due to IKBA GOF mutation | ID with multiple intestinal atresias | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| WIP deficiency | Bloom syndrome | MYSM1 deficiency | Chromosome 10p13-p14 deletion Syndrome | PGM3 deficiency | SAMD9 | Methylene-tetrahydrofolate-dehydrogenase 1 deficiency | Hepatic veno-occlusive disease with immunodeficiency | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ARPC1B deficiency | PMS2 deficiency | MOPD1 deficiency | CHARGE Syndrome | SAMD9L | Vici Syndrome | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Immunodeficiency with centromeric instability and facial anomalies(ICF1, ICF2, ICF3, ICF4) | EXTL3 deficiency | HOIL1 deficiency, HOIP1 deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MCM4 deficiency | Calcium Channel Defects(ORAI-1 deficiency, STIM1 deficiency) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| RNF168 deficiency | Hennekam-lymphangiectasia-lymphedema syndrome | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| POLE1 deficiency | STAT5b deficiency | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| POLE2 deficiency | Kabuki Syndrome | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| NSMCE3 deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ERCC6L2(Hebo deficiency) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ligase 1 deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| GINS1 deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Wiskott-Aldrich Syndrome
- Wiskott–Aldrich syndrome (WAS) is a rare X-linked Recessive primary immunodeficiency disorder characterized by the triad of eczema, microthrombocytopenia, and often recurrent infections caused by mutation of WASp gene.[1]
- WASp is involved in actin polymerization and associated coupling of receptor engagement, signaling events, and cytoskeletal rearrangement.[2]
- Allogeneic stem cell transplantation is the only curative treatment for Wiskott-Aldrich syndrome.[3]
X-linked thrombocytopenia (XLT)
Presents with mild eczema and/or infections, it is suspected to be a variant of WAS.Patients with XLT shown to have mutations in the (WAS)Wiskott-Aldrich syndrome protein gene.
X-linked thrombocytopenia (XLT) should be suspected in a male with:
- Congenital thrombocytopenia (5,000-50,000 platelets/mm3).
- Small platelet size (platelet volume <7.5 fL).
- Absence of other clinical findings of Wiskott-Aldrich syndrome.
- Family history of one or more maternally related males with a WAS-related phenotype or disorder.
- Decreased or absent WASP by flow cytometry or western blotting..
- Some affected individuals have near-normal amounts of WAS.
WIP DEFICIENCY
NEED TO COMPLETE THIS (WIP)WISKOTT-ALDRICH-INTERACTING PROTEIN; gene :WIPF1 is located on 2q31.1 . lymphocytes, WASP is almost totally complexed with the WASP-interacting protein (WIP). A major function of WIP is to stabilize WASP and prevent its degradation. WASP protein levels, but not mRNA levels, are severely reduced in T cells [4]
ARPC1B DEFICIENCY
- ARPC1B gene (ACTIN-RELATED PROTEIN 2/3 COMPLEX, SUBUNIT 1B) is located on 7q22.1 and its deficieny leads to PLTEID(Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease)
- The ARP2/3 protein complex is involved in the control of actin polymerization in cells. The human complex consists of 7 subunits, including the actin-related proteins ARP2 and ARP3 .[5]
- PLTEID is an autosomal recessive immune-mediated inflammatory disease with highly variable manifestations. More severely affected individuals have recurrent infections, vasculitis, and thrombocytopenia, whereas other patients have mild vasculitis and normal numbers of small platelets without severe infections.
- Laboratory studies show platelets with abnormal shape, decreased dense granules, and impaired spreading ability, as well as immune dysregulation with increased eosinophils, B cells, IgA and IgE, and autoantibodies [6]
ATAXIA-TELANGIECTASIA
- Ataxia-telangiectasia (AT) is an autosomal recessive characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, radiosensitivity, predisposition to lymphoid malignancies and immunodeficiency
- The ATM gene is related to a family of genes involved in cellular responses to DNA damage and/or cell cycle control with defects in both cellular and humoral immunity [7].
- ATM gene is located on 11q22.3.
- Diagnosis is usually achieved by physical examination and identification of both ataxia and oculo-cutaneous telangiectasia, this is then followed by laboratory tests for low levels of IgA, IgG2, IgG4, and IgE.
- They may also have a low lymphocyte count and other immunological abnormalities.
- This can then be followed by cytogenetic and molecular testing to confirm the diagnosis.
- MRI and CT scans may show signs of cerebellar atrophy.
Nijmegen breakage Syndrome
- Nijmegen breakage syndrome (NBS) is caused by mutation in the NBS1 gene on chromosome 8q21 which is inherited as an Autosomal Recessive disorder.
- It is characterized by microcephaly, growth retardation, immunodeficiency, and predisposition to cancer.
- It is phenotypically indistinguishable from Berlin breakage syndrome.Both are autosomal recessive chromosomal instability syndromes.
- Ataxia-telangiectasia variant-1 is the designation applied to the Nijmegen breakage syndrome.
BLOOM SYNDROME
- It is caused by the mutation in the BLM gene encoding DNA helicase RecQ protein-like-3 (RECQL3) on chromosome 15q26.
- also called Bloom-Torre-Machacek syndrome or congenital telangiectatic erythema, is a rare autosomal recessive inherited disorder characterized by genomic instability and predisposition to the development all types of cancer.
- The most prominent features include growth deficiency of prenatal onset, mild immunodeficiency, excessive photosensitivity with facial lupus-like skin lesions, type 2 diabetes mellitus and hypogonadism.
- Laboratory diagnosis of Bloom syndrome by detecting mutations in BLM .
PMS2 deficiency
- PMS2 stands for POSTMEIOTIC SEGREGATION INCREASED, S. CEREVISIAE,
- PMS2 gene is located on chromosome 7p22.1
- PMS2 is a gene that encodes for DNA repair proteins involved in mismatch repair
- Its Deficiency is inherited as Autosomal Recessive pattern which leads to Colorectal cancer, hereditary nonpolyposis akaMismatch repair cancer syndrome[8]
Immunodeficiency with centromeric instability and facial anomalies(ICF1, ICF2, ICF3, ICF4)
- ICF is caused by mutation in the ZBTB24 gene on chromosome 6q21; ICF3 is caused by mutation in the CDCA7 gene on chromosome 2q31; and ICF4 is caused by mutation in the HELLS gene on chromosome 10q23.
- It is an autosomal recessive disease presenting with immunodeficiency, mild facial dysmorphism, growth retardation, failure to thrive, and psychomotor retardation.
- Serum levels of IgG, IgM, IgE, and/or IgA are low.
- Recurrent infections are the presenting symptom, usually in early childhood.
- The differentials include Bloom syndrome, ataxia-telangiectasia, and Nijmegen breakage syndrome
- Treatment almost always includes regular infusions of immunoglobulins, mostly intravenously
- Recently, bone marrow transplantation has been tried.
MCM4 deficiency
- MCM stands for MINICHROMOSOME MAINTENANCE, S. CEREVISIAE, HOMOLOG OF 4
- Deficiency caused by homozygous mutation in the MCM4 gene located on 8q11.21 [9]
- Tt is a variant of familial glucocorticoid deficiency (FGD), an autosomal recessive form of adrenal failure
- MCM4 is one part of a MCM2-7 complex whic functions as the replicative helicase essential for normal DNA replication and genome stability in all eukaryotes
- It characterized by adrenal insufficiency, short stature, and NK cell deficiency.
- The NK cell deficiency accounts for the patients' recurrent viral illnesses
- Patients have typical biochemical features of FGD, with isolated glucocorticoid deficiency, raised ACTH, and normal renin and aldosterone.
- Affected individuals with adrenal insufficiency requiring corticosteroid replacement therapy
RNF168 deficiency
- IT STANDS FOR RING FINGER PROTEIN 168(RNF168)
- Gene is located on chromosome 3q29
- It codes E3 ubiquitin ligase which is critical for Double strand DNA breaks repair.[10]
- Mutation of this gene leads to RIDDLE syndrome.
- This sydrome is inherited as an Autosomal Recessive pattern
- RIDDLE (radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties) syndrome is an immunodeficiency disorder that primarily manifests as an immunoglobulin deficiency,also present with nonimmunological characteristics including short stature and motor control problems
POLE1 deficiency
- POLYMERASE, DNA, EPSILON-1; POLE1
- Gene location: 12q24.33
- gene function: POLE gene encodes the catalytic subunit of DNA polymerase epsilon
- Inheritance pattern: AR
- Disease:Facial dysmorphism-immunodeficiency-livedo-short stature syndrome (FILS syndrome)[11]
- If the pole gene mutation is inherited as an autosomal dominant patter then it leads to COLORECTAL CANCER, SUSCEPTIBILITY TO, 12
POLE2 deficiency
POLYMERASE, DNA, EPSILON-2; POLE2 14q21.3 involved in both DNA replication and DNA repair, AR Mutation in the POLE2 Gene Causing Combined Immunodeficiency
NSMCE3 deficiency
- NONSTRUCTURAL MAINTENANCE OF CHROMOSOMES ELEMENT 3 HOMOLOG; NSMCE3
- The NSMCE3 gene encodes a component of the SMC5/SMC6complex, which is essential for responses to DNA damage and chromosome segregation during cell division
- 15q13.1
- AR
- Lung disease, immunodeficiency, and chromosome breakage syndrome
- Defective T and B cell function and acute respiratory distress syndrome in early childhood.
ERCC6L2(Hebo deficiency)
- HEBO stands for HELICASE MUTATED IN BONE MARROW FAILURE
- ERCC6L2 gene is located on 9q22.32 ERCC6L2 belongs to a family of helicases
- the gene is involved inchromatin unwinding, transcription regulation, and DNA recombination, translocation, and repair
- Mutation of this gene leads to Bone marrow failure syndrome 2
- It is inherited as an autosomal pattern
- Characterized by trilineage bone marrow failure, learning disabilities, and microcephaly
Ligase 1 deficiency
LIGASE I, DNA, ATP-DEPENDENT; LIG1 19q13.33 LIG1 functions at the replication fork to join Okazaki fragments during replication of lagging strand DNA mutation of this gene leads to RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE (formerly called as DNA LIGASE I DEFICIENCY Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents. [14]
GINS1 deficiency
- gene :GINS1
- location : 20p11.21
- protein: GINS complex
- Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency
Immuno-osseous dysplasias
Cartilage Hair Hypoplasia !
- Also known as METAPHYSEAL CHONDRODYSPLASIA
- It is caused by homozygous or compound heterozygous mutation in the RMRP gene on chromosome 9p13.
- The gene endoribonuclease RNase MRP consists of an RNA molecule bound to several proteins
- It has two functions :cleavage of RNA in mitochondrial DNA synthesis and nucleolar cleaving of pre-rRNA.[16]
- Muatation is nherited as an Autosomal Recessive pattern characterized by short-limbed short stature and fine, sparse hair
- It also includes ligamentous laxity, defective immunity, hypoplastic anemia, and neuronal dysplasia of the intestine.
- CHH is diagnosed clinically by observing fine and often sparse hair in an individual with short stature with disproportionally short limbs.
- Radiographic findings are helpful in the work-up of an individual with suspected skeletal dysplasia.
- The metaphyseal ends are abnormal in CHH and appear as scalloped, irregular surfaces that may contain cystic areas on routine radiographs[17]
- Genetic analysis of the RMRP gene confirms the diagnosis
Schimke Syndrome
- Schimke immuno-osseous dysplasia (SIOD) is a rare autosomal recessive spondylo-epiphyseal dysplasia Schimke immunoosseous dysplasia (SIOD) is caused by homozygous or compound heterozygous mutation in the SMARCAL1 gene on chromosome 2q25.
- Mutations in the gene encoding the chromatin remodeling protein, SMARCAL1 (SWI/SNF2-related matrix-associated, actin-dependent regulator of chromatin
- it is autosomal recessive condition, which features skeletal, renal, and immune abnormalities.[19]
- characterized by short stature (often with prenatal growth deficiency), spondyloepiphyseal dysplasia, defective cellular immunity, and progressive renal failure
- The diagnosis should be considered in patients with short stature and immunodeficiency.
- Renal function should be assessed if the diagnosis is suspected.
- Radiographs for the characteristic bony anomalies should be performed.
MYSM1 deficiency !
- MYSM1 gene is located on 1p32.1
- Myb-like, SWIRM, and MPN domain 1 (MYSM1) is a transcriptional regulator mediating histone deubiquitination[20]
- Its deficiency leads to Bone marrow failure syndrome 4.
- MYSM1 deficiency is associated with developmental aberrations, progressive Bone maarow failure with myelodysplastic features, and increased susceptibility to genotoxic stress.
- Hematopoiteic stem cell transplant is a curative therapy for patients with MYSM1 deficiency.
MOPD1 deficiency
- akaTaybi-Linder syndrome
- RNU4ATAC gene ,encoding a small nuclear RNA (snRNA) component of the U12-dependent(minor) spliceosome on chromosome 2q14.
- It is caused by mutations in the RNU4ATAC gene and is inherited in an autosomal recessive manner
- Microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1) is a genetic condition that is mainly characterized by intrauterine and post-natal growth retardation[21]
- An abnormally small head size (microcephaly); abnormal bone growth (skeletal dysplasia); distinctive facial features; and brain anomalies
- Diagnosis is made on the basis of the clinical and radiological phenotype, with common radiological features including short tubular bones, enlarged metaphyses, vertebral and pelvic anomalies, elongated clavicles, bowing of the long bones and cleft vertebral arches
- There are no specific treatments for MOPD1
- Treatment is supportive only.
- The prognosis is poor with most affected individuals dying within the first year of life
EXTL3 deficiency
- EXTL3 stands for EXOSTOSIN-LIKE GLYCOSYLTRANSFERASE 3
- EXTL3 regulates the biosynthesis of heparan sulfate (HS), important for both skeletal development and hematopoiesis, through the formation of HS proteoglycans (HSPGs)
- Missense mutations in the EXTL3 gene located on chromosome 8p21.1
- Mutation of this gene leads to a syndrome called immunoskeletal dysplasia with neurodevelopmental abnormalities
- Affected individuals presented with variable skeletal abnormalities and neurodevelopmental defects.
Thymic Defects with additional congenital anomalies
DiDeorge Syndrome
- Haploinsufficiency of the TBX1 gene,in particular is responsible for most of the physical malformations
- This deletion leads to efective development of the 3rd and 4th pharyngeal pouch system
- Haploinsufficiency of the TBX1 gene,in particular is responsible for most of the physical malformations
- Chromosome 22q11.2 deletion syndrome (22qDS) includes DGS and other similar syndromes, such as velocardiofacial syndrome
- The classic triad of features of DGS on presentation is conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia, although the phenotype is variable.
- Palatal abnormalities and developmental delay are common Immunodeficiency is common in patients with DGS and can range from recurrent sinopulmonary infections (partial DGS) to severe combined immunodeficiency (SCID; complete DGS).
- The severity of the immunodeficiency is The diagnosis of and evaluation for DGS should occur for any neonate with a conotruncal heart lesion, hypocalcemia, and/or cleft palaterelated to the degree of thymic hypoplasia[23]
- The diagnosis of DGS is based upon reduced numbers of CD3+ T cells, combined with either characteristic clinical findings or a demonstrated deletion in chromosome 22q11.2
- Also detected by SCID newborn screening (NBS) using an assay for T cell receptor excision circles (TRECS), a biomarker of T cell development[24]
- Treatment includes supplementation with vitamin D or calcium and with parathyroid hormone
- Thymus tissue transplantation, bone marrow transplant, stem cell transplant, or transplant of disease-fighting blood cells may be necessary.
- Hematopoietic cell transplantation (HCT) is a suitable, technically easier, and more readily available alternative to thymic transplantation in the patient with complete DGS who has an HLA-identical donor
TBX1 deficiency
- TBX1 gene is located on 22q11.21
- T-box transcription factor TBX1 also known as T-box protein 1
- The TBX1 gene provides instructions for making a protein called T-box 1
- Genes in the T-box family play important roles in the formation of tissues and organs during embryonic development
- CONOTRUNCAL ANOMALY FACE SYNDROME/VELOCARDIOFACIAL SYNDROME and DIGEORGE SYNDROME
Chromosome 10p13-p14 deletion Syndrome
- Chromosome 10, monosomy 10p is a rare chromosomal disorder in which the end (distal) portion of the short arm (p) of chromosome 10 is missing (deleted or monosomic)
- The severity of symptoms may be variable, depending upon the exact size or location of the deletion on chromosome 10p.
- Clinical features often include severe intellectual disability; postnatal growth retardation, distinctive malformations of the skull and craniofacial region.
- A short neck and/or congenital heart defects are also present.
- Monosomy 10p is also frequently associated with growth delays after birth, resulting in short stature
- Several cases have also been reported in which affected individuals have some features of DiGeorge syndrome (DGS)
- A diagnosis of chromosome 10, monosomy 10p may be suggested before birth (prenatally) by tests such as amniocentesis or chorionic villus sampling (CVS)
- The treatment of affected individuals is symptomatic and supportive.
CHARGE Syndrome
CHARGE syndrome stands for CHARGE ASSOCIATION--COLOBOMA, HEART ANOMALY, CHOANAL ATRESIA, RETARDATION, GENITAL AND EAR ANOMALIES
Caused by heterozygous mutation in the CHD7 on chromosome 8q12.
CHD7 is essential for the formation of multipotent migratory neural crest, a transient cell population that is ectodermal in origin but undergoes a major transcriptional reprogramming event to acquire a remarkably broad differentiation potential and ability to migrate throughout the body, giving rise to craniofacial bones and cartilages, the peripheral nervous system, pigmentation, and cardiac structures
Inherited as an Autonsomal Dominant pattern Characterized by a pattern of congenital anomalies including choanal atresia and malformations of the heart, inner ear, and retina
Hyper-IgE syndromes
(HIES)Job Syndrome
- Autosomal dominant hyper-IgE recurrent infection syndrome is caused by heterozygous mutation in the STAT3 gene on chromosome 17q21
- Hyper-IgE recurrent infection syndrome is a primary immunodeficiency disorder characterized by chronic eczema, recurrent Staphylococcal infections, increased serum IgE, and eosinophilia.
- Patients have a distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints, and bone fractures
- STAT3 is important in the signaling induced by multiple families of cytokines, hormones, and growth factors, although the precise mechanisms that unify the infectious, dermatologic, skeletal, and immunologic features of this disorder are not yet known
- Laboratory abnormalities include elevated total serum IgE levels, typically ranging from 1000 to >50,000 int. units/mL, and variable eosinophilia.
- The diagnosis of HIES is based upon the presence of suggestive clinical and laboratory findings.
- The diagnosis can be confirmed by molecular testing.
- Management of patients with HIES is focused on skin care, prevention of infection, prompt and complete treatment of infections, and control of pulmonary complications
Comel Netherton Syndrome
- Rare autosomal recessive disorder of cornification caused by mutations in the serine protease inhibitor of Kazal type 5 gene (SPINK5)on chromosome 5q32.
- SPINK5 encodes a multidomain serine protein kinase known as lymphoepithelial Kazal type inhibitor (LEKTI) expressed in epithelial and mucosal surfaces
- Among the proteases it directly inhibits are several kallikreins, especially kallikrein 5 (KLK5). Kallikreins are critical epidermal proteases, important for regulating skin desquamation
- It is clinically characterized by the classic triad of congenital ichthyosiform erythroderma, a specific hair shaft abnormality termed trichorrhexis invaginata ("bamboo hair"), and an atopic diathesis
- Many NS patients exhibit absent LEKTI staining in the epidermis
- Genetic testing will identify a germline SPINK5 mutation and confirm the diagnosis in approximately 66 to 75 percent of cases
- There is no specific therapy for NS. it is mainly supportive The erythrodermic newborn with NS has a very high risk of potentially life-threatening complications, such as hypernatremic dehydration, sepsis, and hypothermia
PGM3 deficiency
Dyskeratosis congenita (DKC)
Dyskeratosis congenita
- X-linked dyskeratosis congenita (DKCX) is caused by mutation in the DKC1 gene on chromosome Xq28
- The disorder is caused by defects in the maintenance of telomeres
- Mutations in genes that maintain telomere length in rapidly dividing cells lead to premature cell death, senescence, or genomic instability,
- It is characterized as a triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa
COATS plus syndrome
- cerebroretinal microangiopathy with calcifications and cysts-1 (CRMCC1) is also known as COATS plus syndrome
- caused by compound heterozygous mutation in the CTC1 gene on chromosome 17p13.
- Inherited as an Autoosomal recessive pattern
- characterized primarily by intracranial calcifications, leukodystrophy, and brain cysts, resulting in spasticity, ataxia, dystonia, seizures, and cognitive decline
SAMD9
SAMD9L
References
- ↑ Buchbinder D, Nugent DJ, Fillipovich AH (2014). "Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments". Appl Clin Genet. 7: 55–66. doi:10.2147/TACG.S58444. PMC 4012343. PMID 24817816.
- ↑ Buchbinder D, Nugent DJ, Fillipovich AH (2014). "Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments". Appl Clin Genet. 7: 55–66. doi:10.2147/TACG.S58444. PMC 4012343. PMID 24817816.
- ↑ Muñoz A, Olivé T, Martinez A, Bureo E, Maldonado MS, Diaz de Heredia C, Sastre A, Gonzalez-Vicent M (September 2007). "Allogeneic hemopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON)". Pediatr Hematol Oncol. 24 (6): 393–402. doi:10.1080/08880010701454404. PMID 17710656.
- ↑ Pawłowski R (1991). "Distribution of common phenotypes of sperm diaphorase (DIA3) in the Polish population". Hum. Hered. 41 (4): 279–80. doi:10.1159/000154013. PMID 1783416.
- ↑ Volkmann N, Amann KJ, Stoilova-McPhie S, Egile C, Winter DC, Hazelwood L, Heuser JE, Li R, Pollard TD, Hanein D (September 2001). "Structure of Arp2/3 complex in its activated state and in actin filament branch junctions". Science. 293 (5539): 2456–9. doi:10.1126/science.1063025. PMID 11533442.
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- ↑ Nicolaides NC, Papadopoulos N, Liu B, Wei YF, Carter KC, Ruben SM, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM (September 1994). "Mutations of two PMS homologues in hereditary nonpolyposis colon cancer". Nature. 371 (6492): 75–80. doi:10.1038/371075a0. PMID 8072530.
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- ↑ Tamaro M, Dolzani L, Monti-Bragadin C, Sava G (May 1986). "Mutagenic activity of the dacarbazine analog p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt in bacterial cells". Pharmacol Res Commun. 18 (5): 491–501. PMID 3526359.
- ↑ Rickenbacher J (1968). "The importance of the regulation for the normal and abnormal development. Experimental investigations on the limb buds of chick embryos". Biol Neonat. 12 (1): 65–87. PMID 4966312.
- ↑ Tummala H, Kirwan M, Walne AJ, Hossain U, Jackson N, Pondarre C, Plagnol V, Vulliamy T, Dokal I (February 2014). "ERCC6L2 mutations link a distinct bone-marrow-failure syndrome to DNA repair and mitochondrial function". Am. J. Hum. Genet. 94 (2): 246–56. doi:10.1016/j.ajhg.2014.01.007. PMC 3928664. PMID 24507776.
- ↑ Barnes DE, Tomkinson AE, Lehmann AR, Webster AD, Lindahl T (May 1992). "Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents". Cell. 69 (3): 495–503. PMID 1581963.
- ↑ Cottineau J, Kottemann MC, Lach FP, Kang YH, Vély F, Deenick EK, Lazarov T, Gineau L, Wang Y, Farina A, Chansel M, Lorenzo L, Piperoglou C, Ma CS, Nitschke P, Belkadi A, Itan Y, Boisson B, Jabot-Hanin F, Picard C, Bustamante J, Eidenschenk C, Boucherit S, Aladjidi N, Lacombe D, Barat P, Qasim W, Hurst JA, Pollard AJ, Uhlig HH, Fieschi C, Michon J, Bermudez VP, Abel L, de Villartay JP, Geissmann F, Tangye SG, Hurwitz J, Vivier E, Casanova JL, Smogorzewska A, Jouanguy E (May 2017). "Inherited GINS1 deficiency underlies growth retardation along with neutropenia and NK cell deficiency". J. Clin. Invest. 127 (5): 1991–2006. doi:10.1172/JCI90727. PMC 5409070. PMID 28414293.
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