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3.
J AAPOS ; 22(4): 323-325, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29550517

RESUMO

Heterozygous mutation in the PACS1 (phosphofurin acidic cluster sorting proteins 1) gene is a known cause of developmental delay, multiple congenital anomalies, dysmorphism, and ocular abnormalities. We present the case of an affected 10-year-old girl, conceived by assisted reproductive technology, who has ocular coloboma and findings characteristic of PACS1 mutation.

4.
Am J Ophthalmol Case Rep ; 7: 102-106, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29260090

RESUMO

Purpose: The genetic causes of anophthalmia, microphthalmia and coloboma remain poorly understood. Missense mutations in Growth/Differentiation Factor 3 (GDF3) gene have previously been reported in patients with microphthalmia, iridial and retinal colobomas, Klippel-Feil anomaly with vertebral fusion, scoliosis, rudimentary 12th ribs and an anomalous right temporal bone. We used whole exome sequencing with a trio approach to study a female with unilateral anophthalmia, kyphoscoliosis and additional skeletal anomalies. Observations: Exome sequencing revealed that the proposita was heterozygous for c.796C > T, predicting p.Arg266Cys, in GDF3. Sanger sequencing confirmed the mutation and showed that the unaffected mother was heterozygous for the same missense substitution. Conclusions and importance: Although transfection studies with the p.Arg266Cys mutation have shown that this amino acid substitution is likely to impair function, non-penetrance for the ocular defects was apparent in this family and has been observed in other families with sequence variants in GDF3. We conclude p.Arg266Cys and other GDF3 mutations can be non-penetrant, making pathogenicity more difficult to establish when sequence variants in this gene are present in patients with structural eye defects.

6.
Hum Mutat ; 37(8): 786-93, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27120018

RESUMO

Retinoic acid (RA) signaling plays a key role in the development and function of several systems in mammals. We previously discovered that the de novo mutations c.1159C>T (p.Arg387Cys) and c.1159C>A (p.Arg387Ser) in the RA Receptor Beta (RARB) gene cause microphthalmia and diaphragmatic hernia. However, the natural history of affected subjects beyond the prenatal or neonatal period was unknown. Here, we describe nine additional subjects with microphthalmia who have de novo mutations in RARB, including the previously described p.Arg387Cys as well as the novel c.887G>C (p.Gly296Ala) and c.638T>C (p.Leu213Pro). Moreover, we review the information on four previously reported cases. All subjects who survived the neonatal period (n = 10) displayed severe global developmental delay with progressive motor impairment due to spasticity and/or dystonia (with or without chorea). The majority of subjects also showed Chiari type I malformation and severe feeding difficulties. We previously found that p.Arg387Cys and p.Arg387Ser induce a gain-of-function. We show here that the p.Gly296Ala and p.Leu213Pro RARB mutations further promote the RA ligand-induced transcriptional activity by twofold to threefold over the wild-type receptor, also indicating a gain-of-function mechanism. These observations suggest that precise regulation of RA signaling is required for brain development and/or function in humans.


Assuntos
Mutação com Ganho de Função , Deficiência Intelectual/genética , Transtornos dos Movimentos/genética , Receptores do Ácido Retinoico/genética , Adolescente , Criança , Pré-Escolar , Distúrbios Distônicos , Feminino , Humanos , Recém-Nascido , Masculino , Modelos Moleculares , Mutação de Sentido Incorreto , Conformação Proteica , Receptores do Ácido Retinoico/química , Ativação Transcricional
7.
Cell ; 161(3): 634-646, 2015 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-25910211

RESUMO

Gestational vitamin A (retinol) deficiency poses a risk for ocular birth defects and blindness. We identified missense mutations in RBP4, encoding serum retinol binding protein, in three families with eye malformations of differing severity, including bilateral anophthalmia. The mutant phenotypes exhibit dominant inheritance, but incomplete penetrance. Maternal transmission significantly increases the probability of phenotypic expression. RBP normally delivers retinol from hepatic stores to peripheral tissues, including the placenta and fetal eye. The disease mutations greatly reduce retinol binding to RBP, yet paradoxically increase the affinity of RBP for its cell surface receptor, STRA6. By occupying STRA6 nonproductively, the dominant-negative proteins disrupt vitamin A delivery from wild-type proteins within the fetus, but also, in the case of maternal transmission, at the placenta. These findings establish a previously uncharacterized mode of maternal inheritance, distinct from imprinting and oocyte-derived mRNA, and define a group of hereditary disorders plausibly modulated by dietary vitamin A.


Assuntos
Oftalmopatias Hereditárias/genética , Mutação de Sentido Incorreto , Proteínas Plasmáticas de Ligação ao Retinol/genética , Sequência de Aminoácidos , Animais , Análise Mutacional de DNA , Feminino , Genes Dominantes , Humanos , Masculino , Troca Materno-Fetal , Dados de Sequência Molecular , Linhagem , Penetrância , Gravidez , Proteínas Plasmáticas de Ligação ao Retinol/química , Alinhamento de Sequência , Deficiência de Vitamina A/metabolismo
8.
Obstet Gynecol ; 125(3): 653-62, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25730230

RESUMO

The Perinatal Quality Foundation and the American College of Medical Genetics and Genomics, in association with the American College of Obstetricians and Gynecologists, the Society for Maternal-Fetal Medicine, and the National Society of Genetic Counselors, have collaborated to provide education for clinicians and laboratories regarding the use of expanded genetic carrier screening in reproductive medicine. This statement does not replace current screening guidelines, which are published by individual organizations to direct the practice of their constituents. As organizations develop practice guidelines for expanded carrier screening, further direction is likely. The current statement demonstrates an approach for health care providers and laboratories who wish to or who are currently offering expanded carrier screening to their patients.


Assuntos
Triagem de Portadores Genéticos , Doenças Genéticas Inatas/diagnóstico , Programas de Rastreamento , Medicina Reprodutiva/tendências , Aconselhamento Genético , Humanos , Consentimento Livre e Esclarecido , Testes para Triagem do Soro Materno , Técnicas de Diagnóstico Molecular
9.
Eur J Hum Genet ; 23(3): 337-41, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24939590

RESUMO

We used exome sequencing to study a non-consanguineous family with two children who had anterior segment dysgenesis, sclerocornea, microphthalmia, hypotonia and developmental delays. Sanger sequencing verified two Peroxidasin (PXDN) mutations in both sibs--a maternally inherited, nonsense mutation, c.1021C>T predicting p.(Arg341*), and a paternally inherited, 23-basepair deletion causing a frameshift and premature protein truncation, c.2375_2397del23, predicting p.(Leu792Hisfs*67). We re-examined exome data from 20 other patients with structural eye defects and identified two additional PXDN mutations in a sporadic male with bilateral microphthalmia, cataracts and anterior segment dysgenesis--a maternally inherited, frameshift mutation, c.1192delT, predicting p.(Tyr398Thrfs*40) and a paternally inherited, missense substitution that was predicted to be deleterious, c.947 A>C, predicting p.(Gln316Pro). Mutations in PXDN were previously reported in three families with congenital cataracts, microcornea, sclerocornea and developmental glaucoma. The gene is expressed in corneal epithelium and is secreted into the extracellular matrix. Defective peroxidasin has been shown to impair sulfilimine bond formation in collagen IV, a constituent of the basement membrane, implying that the eye defects result because of loss of basement membrane integrity in the developing eye. Our finding of a broader phenotype than previously appreciated for PXDN mutations is typical for exome-sequencing studies, which have proven to be highly effective for mutation detection in patients with atypical presentations. We conclude that PXDN sequencing should be considered in microphthalmia with anterior segment dysgenesis.


Assuntos
Antígenos de Neoplasias/genética , Anormalidades do Olho/genética , Microftalmia/genética , Mutação , Receptores de Interleucina-1/genética , Substituição de Aminoácidos , Pré-Escolar , Exoma , Anormalidades do Olho/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Microftalmia/diagnóstico , Linhagem , Peroxidases , Fenótipo
10.
J Community Genet ; 5(3): 223-31, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24415495

RESUMO

The knowledge, attitudes, and barriers to Jewish genetic diseases (JGDs) and screening and their relative importance in reproductive decision-making were assessed in a population-based sample of Ashkenazi Jewish young adults in Florida. These adults attended educational screening fairs hosted by The Victor Center for the Prevention of Jewish Genetic Diseases at the University of Miami. Parametric and nonparametric tests were used as appropriate to analyze data from a single group pretest/posttest design. Four hundred twelve individuals (mean age = 24.9; 54.7 % female, 45.3 % male) completed the questionnaires. Participants' level of knowledge increased from pre- to post-intervention (81.4 vs. 91.0 %; p < 0.0001). Concern about the possibility of being a carrier of a JGD was significantly higher after an educational session (5-point Likert scale mean difference = 0.45; p < 0.0001), as was their level of concern regarding having an affected child (mean difference = 0.20; p < 0.0001). The number of participants who agreed or strongly agreed that the test results would not have any influence on their reproductive behavior was lower after the session (17.2 vs. 20.8 %; p < 0.0001). This study demonstrates that an educational carrier screening program increased knowledge and elucidated awareness of the attitudes and barriers toward JGDs and carrier screening.

11.
Case Rep Pediatr ; 2013: 218124, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23691403

RESUMO

We report a patient with Cat eye syndrome (CES) associated with anatomical asplenia. To the best of our knowledge, there have been no prior reports of this association. Screening for asplenia in CES is potentially important, as asplenia places patients at increased risk for life-threatening bacterial infections. Hence patients with CES without a spleen may require the same routine precautions as any other asplenic patients, with penicillin prophylaxis and immunizations to protect against encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis.

12.
Genet Med ; 15(6): 482-3, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23619275

RESUMO

For years, clinicians have offered gene-by-gene carrier screening to patients and couples considering future pregnancy or those with an ongoing pregnancy early in gestation. Examples include ethnic-specific screening offered to Ashkenazi Jewish patients and panethnic screening for cystic fibrosis and spinal muscular atrophy. Next-generation sequencing methods now available permit screening for many more disorders with high fidelity, quick turnaround time, and lower costs. However, instituting these technologies carries with it perils that must be addressed. The basis for the selection of disorders on expanded carrier screening panels should be disclosed. The information provided about disorders with mild phenotypes, variable expression, low penetrance, and/or characterized by an adult onset should be complete and transparent, allowing patients to opt out of receiving these test results. Patients also must be made aware of the concept of residual risk following negative test results. Laboratories have a duty to participate in and facilitate this information transfer.


Assuntos
Testes Genéticos , Heterozigoto , Diagnóstico Pré-Natal , Adulto , Feminino , Testes Genéticos/ética , Testes Genéticos/normas , Humanos , Guias de Prática Clínica como Assunto , Gravidez , Diagnóstico Pré-Natal/ética , Diagnóstico Pré-Natal/normas
13.
Hum Mol Genet ; 22(16): 3250-8, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23591992

RESUMO

The major active retinoid, all-trans retinoic acid, has long been recognized as critical for the development of several organs, including the eye. Mutations in STRA6, the gene encoding the cellular receptor for vitamin A, in patients with Matthew-Wood syndrome and anophthalmia/microphthalmia (A/M), have previously demonstrated the importance of retinol metabolism in human eye disease. We used homozygosity mapping combined with next-generation sequencing to interrogate patients with anophthalmia and microphthalmia for new causative genes. We used whole-exome and whole-genome sequencing to study a family with two affected brothers with bilateral A/M and a simplex case with bilateral anophthalmia and hypoplasia of the optic nerve and optic chiasm. Analysis of novel sequence variants revealed homozygosity for two nonsense mutations in ALDH1A3, c.568A>G, predicting p.Lys190*, in the familial cases, and c.1165A>T, predicting p.Lys389*, in the simplex case. Both mutations predict nonsense-mediated decay and complete loss of function. We performed antisense morpholino (MO) studies in Danio rerio to characterize the developmental effects of loss of Aldh1a3 function. MO-injected larvae showed a significant reduction in eye size, and aberrant axonal projections to the tectum were noted. We conclude that ALDH1A3 loss of function causes anophthalmia and aberrant eye development in humans and in animal model systems.


Assuntos
Aldeído Oxirredutases/genética , Anoftalmia/genética , Códon sem Sentido/genética , Microftalmia/genética , Quiasma Óptico/anormalidades , Nervo Óptico/anormalidades , Aldeído Oxirredutases/metabolismo , Animais , Anoftalmia/metabolismo , Criança , Pré-Escolar , Exoma , Olho/crescimento & desenvolvimento , Olho/patologia , Feminino , Genoma , Homozigoto , Humanos , Lactente , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Masculino , Microftalmia/metabolismo , Análise de Sequência de DNA , Análise de Sequência de RNA , Peixe-Zebra/embriologia , Peixe-Zebra/genética
14.
J Med Genet ; 49(7): 473-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22791840

RESUMO

BACKGROUND: Holoprosencephaly (HPE), the most common malformation of the human forebrain, may result from mutations in over 12 genes. Sonic Hedgehog (SHH) was the first such gene discovered; mutations in SHH remain the most common cause of non-chromosomal HPE. The severity spectrum is wide, ranging from incompatibility with extrauterine life to isolated midline facial differences. OBJECTIVE: To characterise genetic and clinical findings in individuals with SHH mutations. METHODS: Through the National Institutes of Health and collaborating centres, DNA from approximately 2000 individuals with HPE spectrum disorders were analysed for SHH variations. Clinical details were examined and combined with published cases. RESULTS: This study describes 396 individuals, representing 157 unrelated kindreds, with SHH mutations; 141 (36%) have not been previously reported. SHH mutations more commonly resulted in non-HPE (64%) than frank HPE (36%), and non-HPE was significantly more common in patients with SHH than in those with mutations in the other common HPE related genes (p<0.0001 compared to ZIC2 or SIX3). Individuals with truncating mutations were significantly more likely to have frank HPE than those with non-truncating mutations (49% vs 35%, respectively; p=0.012). While mutations were significantly more common in the N-terminus than in the C-terminus (including accounting for the relative size of the coding regions, p=0.00010), no specific genotype-phenotype correlations could be established regarding mutation location. CONCLUSIONS: SHH mutations overall result in milder disease than mutations in other common HPE related genes. HPE is more frequent in individuals with truncating mutations, but clinical predictions at the individual level remain elusive.


Assuntos
Estudos de Associação Genética/métodos , Proteínas Hedgehog/genética , Holoprosencefalia/genética , Mutação , Feminino , Genótipo , Proteínas Hedgehog/metabolismo , Humanos , Masculino , Prosencéfalo/patologia
15.
JIMD Rep ; 6: 1-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23430931

RESUMO

Biochemical testing of hexosaminidase A (HexA) enzyme activity has been available for decades and has the ability to detect almost all Tay-Sachs disease (TSD) carriers, irrespective of ethnic background. This is increasingly important, as the gene pool of those who identify as Ashkenazi Jewish is diversifying. Here we describe the analysis of a cohort of 4,325 individuals arising from large carrier screening programs and tested by the serum and/or platelet HexA enzyme assays and by targeted DNA mutation analysis. Our results continue to support the platelet assay as a highly effective method for TSD carrier screening, with a low inconclusive rate and the ability to detect possible disease-causing mutation carriers that would have been missed by targeted DNA mutation analysis. Sequence analysis performed on one such platelet assay carrier, who had one non-Ashkenazi Jewish parent, identified the amino acid change Thr259Ala (A775G). Based on crystallographic modeling, this change is predicted to be deleterious, as threonine 259 is positioned proximal to the HexA alpha subunit active site and helps to stabilize key residues therein. Accordingly, if individuals are screened for TSD in broad-based programs by targeted molecular testing alone, they must be made aware that there is a more sensitive and inexpensive test available that can identify additional carriers. Alternatively, the enzyme assays can be offered as a first tier test, especially when screening individuals of mixed or non-Jewish ancestry.

16.
Hum Mutat ; 33(2): 364-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22095910

RESUMO

Vax1 and Vax2 have been implicated in eye development and the closure of the choroid fissure in mice and zebrafish. We sequenced the coding exons of VAX1 and VAX2 in 70 patients with anophthalmia/microphthalmia (A/M). In VAX1, we observed homozygosity for two successive nucleotide substitutions c.453G>A and c.454C>A, predicting p.Arg152Ser, in a proband of Egyptian origin with microphthalmia, small optic nerves, cleft lip/palate, and corpus callosum agenesis. This mutation affects an invariant residue in the homeodomain of VAX1 and was absent from 96 Egyptian controls. It is likely that the mutation results in a loss of function, as the mutation results in a phenotype similar to the Vax1 homozygous null mouse. We did not identify any mutations in VAX2. This is the first description of a phenotype associated with a VAX1 mutation in humans and establishes VAX1 as a new causative gene for A/M.


Assuntos
Agenesia do Corpo Caloso/genética , Fenda Labial/genética , Fissura Palatina/genética , Proteínas de Homeodomínio/genética , Microftalmia/genética , Mutação , Fenótipo , Fatores de Transcrição/genética , Substituição de Aminoácidos , Pré-Escolar , Éxons , Frequência do Gene , Células HEK293 , Homozigoto , Humanos , Masculino
17.
BMC Med Genet ; 12: 172, 2011 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-22204637

RESUMO

BACKGROUND: Anophthalmia/microphthalmia (A/M) is caused by mutations in several different transcription factors, but mutations in each causative gene are relatively rare, emphasizing the need for a testing approach that screens multiple genes simultaneously. We used next-generation sequencing to screen 15 A/M patients for mutations in 9 pathogenic genes to evaluate this technology for screening in A/M. METHODS: We used a pooled sequencing design, together with custom single nucleotide polymorphism (SNP) calling software. We verified predicted sequence alterations using Sanger sequencing. RESULTS: We verified three mutations - c.542delC in SOX2, resulting in p.Pro181Argfs*22, p.Glu105X in OTX2 and p.Cys240X in FOXE3. We found several novel sequence alterations and SNPs that were likely to be non-pathogenic - p.Glu42Lys in CRYBA4, p.Val201Met in FOXE3 and p.Asp291Asn in VSX2. Our analysis methodology gave one false positive result comprising a mutation in PAX6 (c.1268A > T, predicting p.X423LeuextX*15) that was not verified by Sanger sequencing. We also failed to detect one 20 base pair (bp) deletion and one 3 bp duplication in SOX2. CONCLUSIONS: Our results demonstrated the power of next-generation sequencing with pooled sample groups for the rapid screening of candidate genes for A/M as we were correctly able to identify disease-causing mutations. However, next-generation sequencing was less useful for small, intragenic deletions and duplications. We did not find mutations in 10/15 patients and conclude that there is a need for further gene discovery in A/M.


Assuntos
Anoftalmia/genética , Fatores de Transcrição Forkhead/genética , Microftalmia/genética , Mutação , Fatores de Transcrição Otx/genética , Fatores de Transcrição SOXB1/genética , Sequência de Aminoácidos , Sequência de Bases , Análise Mutacional de DNA , Deleção de Genes , Duplicação Gênica , Humanos , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA
18.
Curr Opin Ophthalmol ; 22(5): 309-13, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21825993

RESUMO

PURPOSE OF REVIEW: To summarize recent breakthroughs regarding the genes known to play a role in normal ocular development in humans and to elucidate the role mutations in these genes play in anophthalmia and microphthalmia. RECENT FINDINGS: The main themes discussed within this article are the various documented genetic advances in identifying the various causes of anophthalmia and microphthalmia. In addition, the complex interplay of these genes during critical embryonic development will be addressed. SUMMARY: The recent identification of many eye development genes has changed the ability to identify a cause of anophthalmia and microphthalmia in many individuals. Syndrome identification and the availability of genetic testing underscores the desirability of evaluation by a geneticist for all individuals with anophthalmia and microphthalmia in order to provide appropriate management, long-term guidance, and genetic counseling.


Assuntos
Anoftalmia/genética , Microftalmia/genética , Fatores de Transcrição/genética , Anoftalmia/embriologia , Anoftalmia/etiologia , Análise Mutacional de DNA , Proteínas do Olho/genética , Feminino , Fatores de Transcrição Forkhead/genética , Proteínas de Homeodomínio/genética , Humanos , Microftalmia/embriologia , Microftalmia/etiologia , Mutação/genética , Fatores de Transcrição Otx/genética , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/genética , Gravidez , Proteínas Repressoras/genética , Fatores de Transcrição SOXB1/genética , Fator de Crescimento Transformador beta/genética
19.
PLoS Genet ; 7(7): e1002114, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21750680

RESUMO

Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1(tm1a)) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1(tm1a/tm1a)). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1(tm1a/tm1a) embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice.


Assuntos
Anoftalmia/genética , Proteína Morfogenética Óssea 1/antagonistas & inibidores , Mutação , Osteonectina , Síndrome de Waardenburg/genética , Animais , Proteína Morfogenética Óssea 1/genética , Coloboma/genética , Análise Mutacional de DNA , Extremidades/crescimento & desenvolvimento , Olho/crescimento & desenvolvimento , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Osteonectina/genética , Osteonectina/metabolismo , Linhagem , Sindactilia/genética , Xenopus laevis
20.
Genet Med ; 13(5): 437-42, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21285886

RESUMO

PURPOSE: The goal of our study was to determine whether genomic copy number abnormalities (deletions and duplications) affecting genes involved in eye development contributed to the etiology of anophthalmia, microphthalmia, and coloboma. METHODS: The affected individuals were evaluated for the presence of deletions and duplications in genomic DNA by a very high-resolution array comparative genomic hybridization. RESULTS: Array analysis of 32 patients detected one case with a deletion encompassing the renal-coloboma syndrome associated gene PAX2. Nonpolymorphic copy number changes were also observed at several candidate chromosomal regions, including 6p12.3, 8q23.1q23.2, 13q31.3, 15q11.2q13.1, 16p13.13, and 20q13.13. CONCLUSIONS: This study identified the first patient with the typical phenotype of the renal-coloboma syndrome caused by a submicroscopic deletion of the coding region of the PAX2 gene. The finding suggests that PAX2 deletion testing should be performed in addition to gene sequencing as a part of molecular evaluation for the renal-coloboma syndrome. Array comparative genomic hybridization testing of 32 affected individuals showed that genomic deletions and duplications are not a common cause of nonsyndromic anophthalmia, microphthalmia, or coloboma but undoubtedly contribute to the etiology of these eye anomalies. Therefore, array comparative genomic hybridization testing represents an important and valuable addition to candidate gene sequencing in research and diagnostics of ocular birth defects.


Assuntos
Hibridização Genômica Comparativa , Anormalidades do Olho/genética , Deleção Cromossômica , Duplicação Cromossômica/genética , Variações do Número de Cópias de DNA/genética , Deleção de Genes , Humanos , Fator de Transcrição PAX2/genética
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