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Scientific collaboration yields many advantages, especially in fields that require interdisciplinary approaches, as it fosters the sharing of knowledge and resources and is essential for the implementation of complex projects. The concept of scientific internationalism emerged around the 1900s, emphasizing that science surpasses national boundaries and promotes global peace and collaboration. International scientific cooperation is halted by geopolitical tensions and conflicts, such as World War II and the Cold War. Nevertheless, many examples show that scientific collaboration can surpass conflicts and bring scientific and society development, such as in the cases of the Tick-borne Encephalitis vaccine, the Apollo-Soyuz test project and more recently the international endeavour for COVID-19 vaccine development. In this contest, UN and WHO have an imporant role to promote peace and scientific cooperation, examplified by the 16th Sustainable Development Goal, to “Promote just, peaceful and inclusive societies”.

Scientific collaboration is more common now than it was before. In many areas of biomedical science, collaborations between researchers with different scientific backgrounds and perspectives have enabled researchers to address complicated questions and solve complex problems.

Analytical laboratory results greatly influence medical diagnosis, about 70% of medical decisions are based on laboratory results. Quality assurance and quality control are designed to detect and correct errors in a laboratory’s analytical process to ensure both the reliability and accuracy of test results. Unreliable performance can result in misdiagnosis and delayed treatment. Furthermore, improved quality guarantees increased productivity at a lower cost. Quality assurance programmes include internal quality control, external quality assessment, proficiency surveillance and standardization. It is necessary to try to ensure compliance with the requirements of the standards at all levels of the process. The sources of these standards are the International Standards Organization (ISO), national standards bodies, guidelines from professional organisations, accreditation bodies and governmental regulations. Laboratory networks increase the performance of laboratories in support of diagnostic screening programme. It is essential that genetic laboratories of a network have procedures underpinned by a robust quality assurance system to minimize errors and to reassure the clinicians and the patients that international standards are being met. This article provides an overview of the bases of quality assurance and its importance in genetic tests and it reports the EBTNA quality assurance system which is a clear and simple system available for access to adequate standardization of a genetic laboratory’s network.

Cardiovascular disorders include various conditions characterized by morphological and functional defects of the heart and vascular system. Molecular biology techniques (in particular DNA sequencing) have recently offered new insights into the etiology of cardiovascular defects, revealing their association with germline as well as somatic mutations.

Ventricular septal defects (VSDs) are the commonest heart malformations and may affect the membranous or the muscular septum. Clinical presentation depends on the amount of interventricular flow, which is determined by the size of the defect and the relative resistances of the pulmonary and systemic vascular beds. The prevalence of VSD is estimated at about 5% among infants. Many small malformations present at birth may later undergo spontaneous closure. VSD may have autosomal dominant or autosomal recessive inheritance and may exist as isolated forms or as part of a syndrome. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Large-caliber vessels are those with a diameter of 10 mm or more. Most aneurysms remain asymptomatic until they expand or rupture. Aortic aneurysms are of special interest for physicians and scientists because of their prevalence. Aortic aneurysms and dissections account for 1-2% of all deaths in western countries. Expansion and rupture of vascular aneurysms show a strong correlation with hyperlipidemia, hypertension, smoking, sex and age. Heritability estimates have been as high as 70%. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Vascular anomalies (VAs) have phenotypic variability within the same entity, overlapping clinical features between different conditions, allelic and locus heterogeneity and the same disorder can be inherited in different ways. Most VAs are sporadic (paradominant inheritance or de novo somatic or germline mutations), but hereditary forms (autosomal dominant or recessive) have been described. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. The genetic test is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Bicuspid aortic valve (BAV) is a congenital defect in which the aortic valve has two rather than three leaflets. In many patients valve function may be normal but valve decompensation may occur due to other associated congenital abnormalities and secondary valve and aortic complications. Decompensation manifests as stenosis or regurgitation and thoracic aortic aneurysm and dissection. Cystic medial necrosis plays an important role in the pathogenesis of BAV. Prevalence of BAV is estimated at 0.5-2.0%. In children, 70-85% of stenotic aortic valves are bicuspid, compared to at least 50% in adults. BAV has autosomal dominant inheritance. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Marfan-like disorders are inherited conditions with features resembling Marfan syndrome but without a pathogenic variant in FBN1, and/or without a clinical diagnosis of Marfan syndrome according to the Revised Ghent criteria, and/or with a pathogenic variant in a different disease gene. Marfan-like disorders are clinically and genetically heterogeneous and have variable prognosis. They may have autosomal dominant or autosomal recessive patterns of inheritance. The prevalence of most Mar-fan-like disorders is unknown. This Utility Gene Test was prepared on the basis of an analysis of the literature and existing diagnostic protocols. Molecular testing is useful for diagnosis confirmation, as well as differential diagnosis, appropriate genetic counselling and access to clinical trials.

Lymphatic malformations (LMs) show phenotypic variability, as well as clinical and genetic heterogeneity. Inheritance is autosomal dominant, recessive or X-linked and major genes involved in predisposition for LMs are continuously being discovered. The literature also indicates that somatic mutations play an important role in the development of LMs. In fact, activating somatic mutations in PIK3CA have been reported in lymphatic endothelial cells obtained from patients with different kinds of LM. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Cystic hygroma (CH) is characterized by abnormal accumulation of fluid in the region of the fetal neck and is a major anomaly associated with aneuploidy. Morphologically characterized by failure of the lymphatic system to communicate with the venous system in the neck, the clinical manifestations of CH depend on its size and location. Incidence is estimated at one case per 6000-16,000 live births. CH has autosomal dominant or autosomal recessive inheritance. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Stroke is defined as a focal or at times global neurological impairment of sudden onset and presumed vascular origin. 85% of strokes are due to cerebral ischemia and the other 15% to primary intracerebral hemorrhage.

Lesch-Nyhan Disease (LND) is a rare X-linked genetic disease with hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency, due to mutation in the encoding gene, located on the X-chromosome. LND patients exhibit hyperuricemia with stones due to unrecycled purine accumulation and increased synthesis, and a devastating neurological syndrome with dystonia and self-injurious behaviour, choreoathetosis and spasticity. In spite of biochemical and molecular research, the fine connection between the neurological syndrome and HGPRT deficiency is still unclear, though there is consensus regarding brain neurotransmitter dysfunction with few dopaminergic neuron terminals in the striatum. The rarity of the disease makes it difficult to obtain homogeneous population of patients to study. The aim of this paper is to contribute to the understanding of the connection between genotype and phenotype in a cohort of Italian patients, to propose a reliable method of identifying carrier women in affected families, and to provide evidence of a possible link between HGPRT deficiency and altered adenosinergic and serotonergic neurotransmission. Biochemical and mutation analysis is reported in 28 LNS Italian patients from 25 families, with virtually no HGPRT activity and typical LNS phenotype. Genetic analysis identified 24 HPRT mutations, nine of which had never previously been reported, and no mutation hotspots. Carrier females were identified by a new semiquantitative real-time PCR. Studies performed by real-time PCR on knockout mice demonstrated altered adenosinergic and serotonergic pathways, with greatly increased ADORA1A receptor expression, slightly decreased ADORA2A expression and unchanged ADORA2B expression. Increased HTRC2 expression with no significant difference in mRNA editing suggested serotonergic involvement. The different approaches used allowed us to study certain aspects of LND, focusing on mutation analysis in patients and carriers and on simultaneous analysis of biochemical and genetic features. Mouse models elucidated the possible involvement of adenosine and serotonine receptors in the neurotransmission aberration occurring in HGPRT deficiency.

MAGI is concerned with research and diagnosis of rare genetic diseases. It has been operating since 2006 in Italy and abroad. Today it has three centers in Italy, including a medical genetics laboratory specialized in next generation sequencing in Bolzano, a medical genetics laboratory specialized in MLPA in Rovereto (Trento) and a genetic diseases information center at San Felice del Benaco (Brescia). MAGI has also invested outside Italy, setting up non-profit genetics laboratories in countries such as Albania, Russia and in the near future, Kazakhstan.

Inherited eye diseases are a group of conditions with genetic and phenotypic heterogeneity. Advances in ocular genetic research have provided insights into the genetic basis of many eye diseases. Genetic and technological progress is improving the management and care of patients with inherited eye diseases. Diagnostic laboratories continue to develop strategies with high specificity and sensitivity that reduce the costs and time required for genetic testing. The introduction of next generation sequencing technologies has significantly advanced the identification of new gene candidates and has expanded the scope of genetic testing. Gene therapy offers an important opportunity to target causative genetic mutations. There are clinical trials of treatments involving vector-based eye gene therapies, and a significant number of loci and genes now have a role in the diagnosis and treatment of human eye diseases. Applied genetic technology heralds the development of individualized treatments, ushering ophthalmology into the field of personalized medicine. Many therapeutic strategies have demonstrated efficacy in preclinical studies and have entered the clinical trial phase. In this paper we review the topic of genetic testing in inherited eye diseases. We provide some background information about genetic counseling and genetic testing in ophthalmology and discuss how genetic testing can be helpful to patients and families with inherited eye diseases.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for Mendelian glaucomas, a large heterogeneous group of inherited disorders, classified according to age of onset as congenital glaucoma, juvenile glaucoma and age-related glaucoma. Variations in the TEK, MYOC, ASB10, NTF4, OPA1, WDR36 and OPTN genes are inherited in an autosomal dominant manner and variations in the CYP1B1 and LTBP2 genes have autosomal recessive inheritance. The prevalence of congenital glaucoma is estimated at 1-9 per 100 000, that of juvenile glaucoma at 1 per 50 000, while there is insufficient data to establish the prevalence of age-related glaucoma. Clinical diagnosis is based on clinical findings, age of onset, family history, ophthalmological examination, intraocular pressure, gonioscopy and fundoscopy. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

The main constituents of the genus Sideritis are various terpenoids, sterols, coumarins, flavonoid aglycones and glycosides. Sideritis species have been traditionally used as infusions or flavoring agents and in medicine as anti-inflammatory, antiulcer, antimicrobial, antioxidant, antispasmodic and analgesic agents. This paper includes the following sections: Introduction, Description and distribution of Sideritis spp, Pharmacological effects, Toxicity tests, Rationale for use of Sideritis spp. in ophthalmology and Conclusions. The aim is to provide a comprehensive overview on the botanical, phytochemical and pharmacological aspects of the genus Sideritis, and to establish the scientific basis of its pharmacological use. New approaches to using officinal plants have recently yielded significant results. The paper also reviews this information and provides a critical view on the options for exploiting the potential of Sideritis spp. in ophthalmology.

We reviewed the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for non syndromic retinitis pigmentosa (NSRP). NSRP is determined by variations in the ABCA4, AGBL5, ARL2BP, ARL6, BBS2, BEST1, C2orf71, C8orf37, CA4, CDHR1, CERKL, CLRN1, CNGA1, CNGB1, CRB1, CRX, DHDDS, EYS, FAM161A, FSCN2, GUCA1B, HGSNAT, IDH3B, IFT140, IFT172, IMPDH1, IMPG2, KIZ, KLHL7, LRAT, MAK, MERTK, NEK2, NR2E3, NRL, OFD1, PDE6A, PDE6B, PDE6G, POMGNT1, PRCD, PROM1, PRPF3, PRPF31, PRPF4, PRPF6, PRPF8, PRPH2, RBP3, RDH12, RGR, RHO, RLBP1, ROM1, RP1, RP2, RP9, RPE65, RPGR, SAG, SEMA4A, SLC7A14, SNRNP200, SPATA7, TOPORS, TTC8, TULP1, USH2A, ZNF408 and ZNF513 genes. Its overall prevalence is 1 per 4000. It is mostly inherited in an autosomal recessive manner, fewer genes have autosomal dominant or X-linked recessive transmission. Clinical diagnosis is based on clinical findings, ophthalmological examination, best corrected visual acuity (BCVA), slit lamp biomicroscopy, fundus autofluorescence, electroretinography, color vision testing and optical coherence tomography. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of the genetic test for corneal dystrophies and other Mendelian corneal diseases (CDs). CDs are mostly inherited in an autosomal dominant manner (autosomal recessive inheritance is rare). The overall prevalence is currently unknown. CDs are caused by mutations in the AGBL1, CHST6, COL8A2, DCN, GSN, KRT12, KRT3, NLRP1, PAX6, PIKFYVE, PRDM5, SLC4A11, TACSTD2, TCF4, TGFBI, UBIAD1, VSX1, ZEB1, and ZNF469 genes. Clinical diagnosis is based on clinical findings, ophthalmological examination, confocal microscopy and slit-lamp biomicroscopy. The genetic test is useful for confirming diagnosis and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of the genetic test for Mendelian cataract (MC). MC is caused by variations in the AGK, BFSP1, BFSP2, CHMP4B, CRYAA, CRYAB, CRYBA1, CRYBA2, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD, CRYGS, EPHA2, EYA1, FYCO1, FOXE3, FTL, GALK1, GCNT2, GJA3, GJA8, HSF4, LEMD2, LIM2, LSS, MAF, MIP, NHS, PITX3, PAX6, SIPA1L3, SLC16A12, TDRD7, UNC45B, VIM, VSX, and WFS1 genes. The overall prevalence of congenital forms is 71 per 100 000, whereas there is insufficient data to determine the prevalence of the juvenile and age-related forms. Clinical diagnosis is based on clinical findings, age of onset, family history, ophthalmological examination and slit-lamp examination. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by telangiectases and arteriovenous malformations. These lesions cause bleeding, particularly in the nose, gastrointestinal tract and brain. HHT has incomplete penetrance, variable expressivity and genetic heterogeneity. De novo mutations associated with the onset of sporadic HHT have been reported. This Utility Gene Test was prepared on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Tetralogy of Fallot (ToF) combines congenital cardiac defects including ventricular septal defect, pulmonary stenosis, an overriding aorta and right ventricular hypertrophy. Clinical manifestation of this defect depends on the direction and volume of shunting of blood through the ventricular septal defect and the associated right ventricular and pulmonary artery pressures. ToF accounts for 3-5% of congenital heart defects or 0.28 cases every 1000 live births. ToF has autosomal dominant inheritance. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Cavernous cerebral malformations (CCM) are vascular malformations of the brain and spinal cord. CCM affect up to 0.5% of the general population, predisposing to headaches, seizures, cerebral hemorrhage and focal neurological deficit. CCM may be familial or sporadic. Familial forms have autosomal dominant inheritance. This Utility Gene Test was prepared on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Pulmonary stenosis (PS) is a congenital pulmonary valve malformation. It can be classified as valvular, subvalvular or supravalvular. Isolated forms of PS are rare. PS is associated with the development of massive pulmonary arterial dilatation. Patients with PS have a high consanguinity rate and the disorder is highly familial, which is why knowing the genetic aetiology of this defect is important. Prevalence is estimated at about 4/10,000 live births, and incidence at about 10% of all children with congenital heart defects. PS has prevalently autosomal dominant and rarely autosomal recessive inheritance. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Ehlers-Danlos syndrome (EDS) is an umbrella term for various inherited connective tissue disorders associated with mutations in genes involved in extracellular matrix formation. “The 2017 International Classification of Ehlers-Danlos Syndromes and related disorders” identifies 13 clinical types with mutations in 19 distinct genes. The present module focuses on forms with major vascular involvement: vascular EDS (vEDS) caused by heterozygous mutations in COL3A1, “vascular-like” EDS (vlEDS) caused by recurrent mutations in COL1A1, classical EDS with vascular fragility associated with heterozygous mutations in COL5A1, and kyphoscoliotic EDS associated with recessive variations in PLOD1 and FKBP14. The overall prevalence of EDS is estimated between 1/10,000 and 1/25,000 and vEDS accounts for about 5 to 10% of all EDS cases. This Utility Gene Test was prepared on the basis of an analysis of the literature and existing diagnostic protocols. Molecular testing is useful for diagnosis confirmation, as well as differential diagnosis, appropriate genetic counselling and access to clinical trials.

Emberger Syndrome (ES) is a very rare genetic disorder associated with primary lymphedema, myelodysplasia and immunodeficiency. The syndrome has autosomal dominant inheritance with incomplete penetrance. Sporadic cases caused by de novo germinal mutations in the GATA2 gene have also been described. We developed the test protocol on the basis of the latest research findings and diagnostic protocols on lymphatic malformation in ES. The genetic test is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Coarctation of the aorta (CoA) is an inherited narrowing of the proximal descending thoracic aorta. Histological features include localized medial thickening and infolding with superimposed neointimal tissue. CoA is diagnosed by detection of a murmur or hypertension during routine examination. Typical clinical features are delayed or absent femoral pulses and difference in blood pressure between the arm and legs. These symptoms may appear in the first weeks of life or after the neonatal period. CoA accounts for 4-6% of all congenital heart defects and has a reported prevalence of about 4 per 10,000 live births. It is more common in males than females (59% vs 41%). This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Atrioventricular septal defect (AVSD) is a congenital heart defect characterized by a shared atrioventricular junction coexisting with deficient atrioventricular septation. The main morphological characteristic of AVSD is a common atrioventricular canal. The prevalence of AVSD is estimated at 0.31/1000 live births and is higher among subjects with PTPN11 mutations. ASD may have autosomal dominant or autosomal recessive inheritance. This Utility Gene Test was prepared on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Hennekam Syndrome (HS) is a combination of congenital lymphatic malformation, lymphangiectasia and other disorders. It is a very rare disorder with autosomal recessive inheritance. We developed the test protocol “Hennekam Syndrome” on the basis of the latest research findings and diagnostic protocols on lymphatic malformation in HS. The genetic test is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Variants affecting the function of genes in the RAS–mitogen-activated protein kinase (MAPK) signal transduction pathway have been identified as responsible for a group of developmental syndromes known as RASopathies. Noonan (NS) and cardiofaciocutaneous syndromes (CFC) represent the most frequent and best characterized RASopathies. Many cases of RASopathies are associated with lymphatic malformations that finally may result in lymphedema. We developed the test protocol “Lymphedema in RASopathies” on the basis of the latest research findings and diagnostic protocols on lymphatic malformation in RASopathies. The genetic test is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Aortic valve stenosis (AVS) is a congenital aortic defect in which the aortic lumen narrows due to thickening or calcification of the aortic valve without obstructing left ventricular outflow. Depending on the site of obstruction, AVS is classified as valvular, sub-valvular or supra-valvular. The prevalence of AVS is about 3% and increases with age. One in eight persons over the age of 75 years has moderate or severe AVS. AVS has autosomal dominant inheritance. It can be associated with mutations in the following genes: NOTCH1, SMAD6, SMAD4, and ELN. This Utility Gene Test was developed on the basis of the analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials, when available.

We studied the scientific literature and disease guidelines to summarize the clinical utility of genetic testing for lymphedema distichiasis (LD) syndrome. LD is inherited in an autosomal dominant manner, and has unknown prevalence. It is caused by variations in the FOXC2 gene. Clinical diagnosis involves clinical examination, targeted at identifying primary lymphedema (chronic swelling of the extremities) and distichiasis (double row of eyelashes). The genetic test is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

Ebstein anomaly (EA) is a rare congenital tricuspid valve malformation, characterized by downward displacement of the septal leaflet and an atrialized right ventricle. About 80% of cases of EA are non-syndromic; in the other 20%, the anomaly is associated with a chromosomal or Mendelian syndrome. The prevalence of EA is estimated at about 1 per 20,000 live births, and accounts for less than 1% of all congenital heart defects. EA has autosomal dominant inheritance. Likely causative genes are: NKX2-5, MYH7 and TPM1. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, potential risk assessment and access to clinical trials.

Marfan syndrome (MFS) is an inherited connective tissue disorder caused by heterozygous mutations in the FBN 1 gene. Clinical manifestations of MFS include aortic dilatation and dissection, as well as cardiac valvular, ocular, skeletal and neurological manifestations. Prevalence varies from 6 to 20 per 100,000 individuals. Revised Ghent Nosology (2010) is used to establish a clinically based suspected diagnosis to be confirmed by molecular testing. This Utility Gene Test was prepared on the basis of an analysis of the literature and existing diagnostic protocols. Molecular testing is useful for diagnosis confirmation, as well as differential diagnosis, appropriate genetic counselling and access to clinical trials.

Primary lymphedema can be familial (in which more than one member of the same family has a lymphedema phenotype), syndromic (in which lymphedema is one symptom of a complex clinical syndrome) or sporadic (in which an isolated family member has lymphedema). All types of lymphedema are determined by genetic alteration of one or more genes. Not all the genes involved are known.

Molecular diagnosis relieves patients of uncertainty, aids informed decisions about health and reproductive choices, and helps them join clinical trials or access available therapy. Genetic testing by next generation sequencing (NGS) is the suggested choice for a wide variety of disorders with heterogeneous phenotypes, alleles and loci. The development of a NGS service at MAGI Balkans, through the support of a partner, increases the availability of forefront genetic testing in Albania with great advantages for patients and their families. Here we report the NGS tests performed in collaboration with MAGI Euregio, Italy, for the diagnosis of rare genetic disease in seven probands and their families. The diseases/manifestations included ichthyosis, familial adenomatous polyposis, diabetes, syndromic craniosynostosis, fronto-temporal dementia, fragile X syndrome and ataxia. We obtained an overall detection rate of 57%. For 4/7 probands we identified a pathogenic or likely pathogenic variant, while for the others, the results did not completely explain the phenotype. All variants were confirmed by Sanger sequencing. Segregation of the variant with the affected phenotype was also evaluated.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of the genetic test for Best vitelliform macular dystrophy (BVMD). BVMD is mostly inherited in an autosomal dominant manner (autosomal recessive transmission is rare). The overall prevalence is currently unknown. BVMD is caused by mutations in the BEST1 gene. Clinical diagnosis is based on clinical findings, ophthalmological examination, optical coherence tomography, electrooculography and electroretinography. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for ocular coloboma (COI). COI is inherited in an autosomal dominant manner associated with variations in the PAX6, ABCB6 and FZD5 genes and in an autosomal recessive manner associated with variations in the SALL2 gene. Overall prevalence is 1 per 100,000 live births. Clinical diagnosis is based on clinical findings, ophthalmogical examination, family history, fundus examination and electroretinography. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for achromatopsia. The disease has autosomal recessive inheritance, a prevalence of 1/30000-1/50000, and is caused by mutations in the CNGB3, CNGA3, GNAT2, PDE6C, ATF6 and PDE6H genes. Clinical diagnosis is by ophthalmological examination, color vision testing and electrophysiological testing. Genetic testing is useful for confirming diagnosis and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for Bardet- Biedl syndrome (BBS). The disease has autosomal recessive inheritance, a prevalence varying from one in 13 500 to one in 160 000, and is caused by mutations in the ARL6, BBIP1, BBS1, BBS2, BBS4, BBS5, BBS7, BBS9, BBS10, BBS12, CEP290, IFT172, IFT27, LZTFL1, MKKS, MKS1, NPHP1, SDCCAG8, TRIM32, TTC8 and WDPCP genes. The clinical diagnosis of BBS is based on four primary features or three primary features plus two secondary features. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of the genetic test for Bietti crystalline dystrophy (BCD). The disease has autosomal recessive inheritance, a prevalence of 1 per 67 000, and is caused by mutations in the CYP4V2 gene. Clinical diagnosis is based on clinical findings, ophthalmological examination, electroretinography and optical coherence tomography. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of the genetic test for congenital stationary night blindness (CSNB). CSNB is inherited in an autosomal dominant manner in the case of mutations in the GNAT1, PDE6B and RHO genes, in an autosomal recessive manner in the case of mutations in the CABP4, GNB3, GPR179, GRM6, LRIT3, SAG, SLC24A1, TRPM1 and genes and in an X-linked recessive manner in the case of mutations in the CACNA1F and NYX genes. The overall prevalence of CSNB is not known. Clinical diagnosis is based on clinical findings, ophthalmological examination, visual evoked potentials and electroretinography. The genetic test is useful for confirming diagnosis and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for color vision deficiency (CVD). Deuteranopia affects 1 in 12 males and is inherited in an X-linked recessive manner. It is associated with variations in the OPN1LW (OMIM gene: 300822; OMIM disease: 303900) and OPN1MW (OMIM gene: 300821; OMIM disease: 303800) genes. Tritanopia has a prevalence of 1 in 10 000, is inherited in an autosomal dominant manner, and is related to variations in the OPN1SW (OMIM gene: 613522; OMIM disease: 190900) gene. Blue cone monochromatism has a prevalence of 1 in 100 000, is inherited in an X-linked recessive manner and is related to mutations in the OPN1LW (OMIM gene: 300822; OMIM disease: 303700) and OPN1MW (OMIM gene: 300821; OMIM disease: 303700) genes. Clinical diagnosis is based on clinical findings, ophthalmogical examination, family history, electroretingraphy, color vision testing and dark adaptometry. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of the genetic test for cone rod dystrophies (CORDs). CORDs are caused by variations in the ABCA4, ADAM9, AIPL1, C8orf37, CACNA1F, CACNA2D4, CDHR1, CNGA3, CRX, DRAM2, GUCA1A, GUCY2D, HRG4, KCNV2, PDE6C, PITPNM3, POC1B, PROM1, PRPH2, RAB28, RAX2, RIMS1, RPGRIP1, RPGR SEMA4A, TTLL5 genes, with an overall prevalence of 1 per 40 000. Most genes have autosomal recessive inheritance; the others have autosomal dominant or X-linked recessive transmission. Clinical diagnosis is based on clinical findings, color vision testing, ophthalmological examination and electroretinography. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of the genetic test for central areolar choroidal dystrophy (CACD). CACD is mostly inherited in an autosomal dominant manner. Transmission is rarely autosomal recessive. Overall prevalence is currently 1-9 per 100 000. CACD is caused by mutations in the PRPH2 and GUCY2D genes. Clinical diagnosis is based on clinical findings, ophthalmological examination, fluorescein angiography, electroretinography (showing cone dystrophy) and stereo fundus photography. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for Norrie disease. The disease is caused by variations in the NDP gene. Its prevalence is currently unknown. Inheritance is X-linked recessive. Clinical diagnosis is based on clinical findings, color vision testing, optical coherence tomography, ophthalmological examination and electroretinography. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

We reviewed the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for Refsum disease. The disease has autosomal recessive inheritance, unknown prevalence, and is caused by variations in PEX7 and PHYH genes. Clinical diagnosis is based on clinical findings, ophthalmological examination, electroretinography, optical coherence tomography and phytanic acid assay. The genetic test is useful for confirming diagnosis, for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for X-linked juvenile retinoschisis (XJR). The disease has X-linked inheritance, a prevalence that varies from one in 5000 to one in 25000 males, and is caused by mutations in the RS1 gene. Clinical diagnosis is based on clinical findings, ophthalmological examination, electroretinography and optical coherence tomography. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for Doyne honeycomb retinal dystrophy (DHRD). The disease has an autosomal dominant inheritance and is caused by variations in the EFEMP1 gene. There is insufficient data to establish the prevalence of DHRD. Clinical diagnosis is based on clinical findings, ophthalmological examination, electroretinography, fluorescein angiography and optical coherence tomography. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for retinitis punctata albescens/fundus albipunctatus (RPA/FA). RPA and FA are reported to have autosomal dominant or autosomal recessive inheritance and are associated with variations in the PRPH2, RHO, RLBP1 and RDH5 genes. There is insufficient data to establish their prevalence. Clinical diagnosis is based on clinical findings, ophthalmological examination, optical coherence tomography, visual field testing and undetectable or severely reduced electroretinogram amplitudes. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.