Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 894
Filtrar
1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 52-56, 2020 Jan 10.
Artículo en Chino | MEDLINE | ID: mdl-31922597

RESUMEN

OBJECTIVE: To delineate the clinical features,inheritance pattern, and genotype-phenotype correlation of a Chinese patient with a 17q25.3 duplication. METHODS: Whole exome sequencing(WES), chromosomal microarray analysis (CMA), chromosomal karyotyping and fluorescence in situ hybridization (FISH) were employed for the analysis of the proband and his family members. RESULTS: A 5.7 Mb duplication at 17q25.3→qter was identified by WES and CMA in the 4-year-old boy with multiple congenital anomalies, which was classified as a clinically pathogenic variant. This duplication was confirmed by FISH, and was inherited from his unaffected mother who carried a balanced translocation. Further study revealed that his grandmother also carried the balanced translocation but had gestated three healthy children and had no abortion history. His uncle also carried the balanced translocation, while his aunt was normal. CONCLUSION: Above results have enriched the clinical phenotypes of 17q25.3 duplication. Genetic counseling was provided for the family. P4HB, ACTG1, BAIAP2 and TBCD genes may underlie the clinical features for the 17q25.3 duplication.


Asunto(s)
Anomalías Múltiples , Duplicación Cromosómica , Cromosomas Humanos Par 17 , Discapacidades del Desarrollo , Anomalías Múltiples/genética , Adulto , Preescolar , China , Cromosomas Humanos Par 17/genética , Discapacidades del Desarrollo/genética , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Proteínas Asociadas a Microtúbulos , Translocación Genética
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 64-66, 2020 Jan 10.
Artículo en Chino | MEDLINE | ID: mdl-31922600

RESUMEN

OBJECTIVE: To explore the genetic basis of a child with developmental delay and intellectual disability. METHODS: Peripheral blood samples of the child and his parents were collected for routine G-band karyotyping analysis and single nucleotide polymorphism array (SNP array) assay. Amniotic fluid sample was collected during the next pregnancy for prenatal diagnosis. RESULTS: No karyotypic abnormality was found in the child and his parents. SNP array showed that the child has carried a 855.3 kb microduplication in 15q11.2. His mother carried the same duplication but had no phenotypic anomaly. No microdeletion/microduplication was found in his father. Upon prenatal diagnosis, no abnormalities was found with the chromosomal karyotype and SNP array result of the fetus. CONCLUSION: 15q11.2 microduplication may result in developmental delay and intellectual disability, for which CYFIP1 may be a candidate gene. However, the duplication may increase the risk but with a low penetrance. This should attract attention during clinical consultation.


Asunto(s)
Duplicación Cromosómica , Cromosomas Humanos Par 15 , Discapacidad Intelectual , Proteínas Adaptadoras Transductoras de Señales , Niño , Bandeo Cromosómico , Cromosomas Humanos Par 15/genética , Discapacidades del Desarrollo/genética , Femenino , Humanos , Discapacidad Intelectual/genética , Cariotipificación , Masculino , Embarazo , Diagnóstico Prenatal
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(12): 1199-1202, 2019 Dec 10.
Artículo en Chino | MEDLINE | ID: mdl-31813147

RESUMEN

OBJECTIVE: To carry out genetic testing for a boy presenting with mental retardation and hypoplasia. METHODS: Conventional karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism based array (SNP-array) were used to analyze the boy and his parents. RESULTS: SNP-array has detected a 25.7 Mb microduplication at 2q33.3q36.3 in the boy. Chromosomal karyotyping and FISH analysis indicated that his mother had a karyotype of 46,XX,ish ins(11;2) (p15;q33q36), and that the boy has carried an abnormal chromosome 11 derived from the maternal translocation. The karyotype of the boy was ascertained as 46,XY,ish der(11)ins(11;2) (p15;q33q36)mat. CONCLUSION: SNP-array combined with G-banding and FISH can delineate the cryptic translocation and is valuable for the assessment of recurrence risk for subsequent pregnancies.


Asunto(s)
Hipospadias/genética , Discapacidad Intelectual/genética , Cariotipificación , Niño , Bandeo Cromosómico , Duplicación Cromosómica , Femenino , Pruebas Genéticas , Humanos , Hibridación Fluorescente in Situ , Masculino , Polimorfismo de Nucleótido Simple , Embarazo , Translocación Genética
4.
Medicine (Baltimore) ; 98(49): e18258, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31804359

RESUMEN

RATIONALE: Chromosomal duplications are associated with a series of genetic disorders. However, chromosome 5q duplications, especially pure 5q35.3 microduplications, have rarely been reported in the literature. Clinical phenotypes usually depend on the region of chromosome duplicated, its size, and loci. PATIENT CONCERNS: From 2011 to 2017, prenatal amniotic fluid samples were obtained from 6 pregnant women diagnosed with pure 5q35.3 microduplications following different prenatal indications at our center. We followed up the children of these pregnancies and determined their postnatal health conditions. DIAGNOSES: Cytogenetic studies delineated that all patients had normal karyotypes, except for patient 6 who had 46,XX,inv(9)(p11q13). Single-nucleotide polymorphism array results showed 177-269 kb duplications of 5q35.3 (chr5:178728830-178997692) in these cases. All shared similar localization of ADAMTS2. INTERVENTIONS: All pregnant women chose to continue the pregnancies. Follow-up analysis showed that the children presented normal physical and growth developments. OUTCOMES: We described six prenatal cases with similar 5q35.3 duplications involving part of the ADAMTS2 locus with no apparent postnatal phenotypic abnormalities. LESSONS: Our research revealed that partial microduplication of ADAMTS2 (chr5:178728830-178997692) might be benign and not correlate with disorders. And there might exist phenotypic diversities of 5q35.3 duplications.


Asunto(s)
Proteínas ADAMTS/genética , Duplicación Cromosómica , Diagnóstico Prenatal , Adulto , Femenino , Humanos , Recién Nacido , Fenotipo , Polimorfismo de Nucleótido Simple , Embarazo , Resultado del Embarazo
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 989-992, 2019 Oct 10.
Artículo en Chino | MEDLINE | ID: mdl-31598942

RESUMEN

OBJECTIVE: To explore the nature and origin of chromosomal copy number variants (CNVs) in a pedigree affected with mental retardation. METHODS: Genomic CNVs of the proband were analyzed by next generation sequencing (NGS). Chromosomal karyotypes of the proband and his relatives were analyzed with high-resolution karyotyping and fluorescence in situ hybridization (FISH). RESULTS: Clinical phenotypes of the proband and other patients from the pedigree included mental retardation and mild dysmorphism. The results of NGS revealed that the proband carried a 16.24 Mb microduplication at 4p16.3-15.32 and a 2.2 Mb microdeletion at 8p23.3-23.2. Other patients of the pedigree harbored the same variants, while those without the phenotypes did not harbor the variants. The results of high-resolution karyotyping and FISH revealed that the mother of the proband carried a reciprocal translocation between 4p and 8p, and her karyotype was 46,XX,t(4;8)(p16;p23). No karyotypic abnormality was detected in his father. CONCLUSION: The abnormal phenotypes of this pedigree may be attributed to 4p microduplication in conjunct with 8p microdeletion derived from a maternal balanced translocation between 4p and 8p.


Asunto(s)
Aberraciones Cromosómicas , Duplicación Cromosómica , Pruebas Genéticas , Discapacidad Intelectual/genética , Cromosomas Humanos Par 4 , Cromosomas Humanos Par 8 , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Linaje , Fenotipo
6.
Eur J Med Genet ; 62(9): 103558, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31405577

RESUMEN

Microduplications involving 1q32.1 chromosomal region have been rarely reported in literature. Patients with these microduplications suffer from intellectual disability, developmental delay and a number of dysmorphic features, although no clear karyotype/phenotype correlation has yet been determined. In this case report we describe two monochorionic-diamniotic twins with intellectual disability, abnormality of coordination and dysmorphic features associated with a de novo 280 kb mosaic microduplication of 1q32.1 chromosomal region, identified using a Chromosome Microarray Analysis (CMA) and confirmed by quantitative PCR analysis. The duplicated region encompassed entirely three OMIM genes KDM5B (*605393), KLHL12 (*614522), RABIF (*603417) and involved partially SYT2 (*600104). This unique case report allows to redefine the critical 1q32.1 microduplicated region implicated in the ethiopathogenesis of intellectual disability and developmental delay. Furthermore, it suggests that KDM5B gene can have a pivotal role in the development of neurodevelopmental disorders through its demethylase activity.


Asunto(s)
Duplicación Cromosómica , Cromosomas Humanos Par 1/genética , Anomalías Craneofaciales/genética , Discapacidad Intelectual/genética , Histona Demetilasas con Dominio de Jumonji/genética , Trastornos del Neurodesarrollo/genética , Proteínas Nucleares/genética , Proteínas Represoras/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Niño , Anomalías Craneofaciales/patología , Factores de Intercambio de Guanina Nucleótido/genética , Humanos , Discapacidad Intelectual/patología , Masculino , Trastornos del Neurodesarrollo/patología , Sinaptotagmina II/genética , Gemelos
7.
Yi Chuan ; 41(8): 716-724, 2019 Aug 20.
Artículo en Chino | MEDLINE | ID: mdl-31447422

RESUMEN

In order to investigate the genetic variations and the clinical manifestations of a range of congenital ectrodactyly family and to summarize the split hand/foot malformation (SHFM) types and their related pathogenic genes, we conducted phenotypic analyses of patient's limbs by physical and X-ray examination. The haplotypes were analyzed by using the extracted genes from peripheral blood on D10S1709, D10S192, D10S597, D10S1693 and D10S587 loci, and the mutation duplication loci were confirmed by Array-CGH detection. The pathogenic factors and inheritance pattern of SHFM were analyzed based on family investigation and gene analysis. Results demonstrate the proband's phenotype is typically of a congenital SHFM which is manifested by missing bilateral index and middle fingers, short bilateral thumbs, deformed left ring finger with webbing of the skin missing at the middle finger; bilateral big toe with the second and the third toe missing, fourth and fifth toe fusion leading to a deformed toe separated from the first toe by the middle of the foot. The haplotype analyses show that there is a repeat of at least 610 kb in chromosome 10q24.31-10q24.32 region. Array-CGH analysis shows 10q24.31 (102 832 650-103 511 083) ×3. Our results demonstrate that the pathogenic gene variation of ectrodactyly in this family is due to duplication of 10q24.31 (102 832 650~103 511 083). The haplotype 165-251-289-219-102 can be used as a disease marker for detecting 10q24.31~10q24.32 allele for SHFM.


Asunto(s)
Duplicación Cromosómica , Deformidades Congénitas del Pie/genética , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de las Extremidades/genética , Cromosomas Humanos Par 10/genética , Humanos , Linaje
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(7): 724-726, 2019 Jul 10.
Artículo en Chino | MEDLINE | ID: mdl-31302921

RESUMEN

OBJECTIVE: To explore the molecular mechanism of a girl with developmental delay and intellectual disability. METHODS: Chromosomal karotypes of the child and her parents were analyzed with routine G-banding method. Their genomic DNA was also analyzed with array comparative genomic hybridization (aCGH) for chromosomal duplications/deletions. RESULTS: No karyotypic abnormality was detected in the child and her parents, while aCGH has identified a de novo 3.37 Mb deletion at 17p11.2 in the child. CONCLUSION: The child was diagnosed with Smith-Magenis syndrome, for which RAI1 may be the causative gene.


Asunto(s)
Síndrome de Smith-Magenis/genética , Niño , Deleción Cromosómica , Duplicación Cromosómica , Cromosomas Humanos Par 17/genética , Hibridación Genómica Comparativa , Femenino , Humanos , Cariotipificación
9.
Anim Genet ; 50(5): 423-429, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31294880

RESUMEN

A specific white spotting phenotype, termed finching or line-backed spotting, is known for all Pinzgauer cattle and occurs occasionally in Tux-Zillertaler cattle, two Austrian breeds. The so-called Pinzgauer spotting is inherited as an autosomal incompletely dominant trait. A genome-wide association study using 27 white spotted and 16 solid-coloured Tux-Zillertaler cattle, based on 777k SNP data, revealed a strong signal on chromosome 6 at the KIT locus. Haplotype analyses defined a critical interval of 122 kb downstream of the KIT coding region. Whole-genome sequencing of a Pinzgauer cattle and comparison to 338 control genomes revealed a complex structural variant consisting of a 9.4-kb deletion and an inversely inserted duplication of 1.5 kb fused to a 310-kb duplicated segment from chromosome 4. A diagnostic PCR was developed for straightforward genotyping of carriers for this structural variant (KITPINZ ) and confirmed that the variant allele was present in all Pinzgauer and most of the white spotted Tux-Zillertaler cattle. In addition, we detected the variant in all Slovenian Cika, British Gloucester and Spanish Berrenda en negro cattle with similar spotting patterns. Interestingly, the KITPINZ variant occurs in some white spotted animals of the Swiss breeds Evolèner and Eringer. The introgression of the KITPINZ variant confirms admixture and the reported historical relationship of these short-headed breeds with Austrian Tux-Zillertaler and suggests a mutation event, occurring before breed formation.


Asunto(s)
Bovinos/genética , Cromosomas de los Mamíferos , Pigmentación , Proteínas Proto-Oncogénicas c-kit/genética , Animales , Bovinos/clasificación , Duplicación Cromosómica , Estudio de Asociación del Genoma Completo , Variación Estructural del Genoma , Polimorfismo de Nucleótido Simple
10.
Cytogenet Genome Res ; 158(4): 199-204, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31315112

RESUMEN

Here, we report a molecular characterization of a small supernumerary marker chromosome (sSMC) derived from the most proximal region of 13q present in a fetus with coarctation of the aorta at ultrasound examination during prenatal diagnosis. Cultured umbilical cord blood cells showed a de novo extra ring-shaped sSMC in 76% of the cells using a standard banding technique. SNP array revealed a tetrasomy of about 28.4 Mb in the long arm of chromosome 13 from band 13q11 to 13q14.11 in the fetus's cells. Metaphase/interphase FISH using specific probes located at 13q11, 13q12.11, and 13q14.11, respectively, demonstrated that the supernumerary ring chromosome was derived from an inverted duplication of the region 13q11q14.11 with a conventional centromere. To the best of our knowledge, this is the first time that an inverted duplication of the most proximal region 13q11q14.11 in a ring chromosome is characterized. The findings we presented here deepen our understanding of the clinical consequences of tetrasomy in this region and may be of help for further studies of critical regions in chromosome 13.


Asunto(s)
Coartación Aórtica/genética , Duplicación Cromosómica/genética , Cromosomas Humanos Par 13/genética , Enfermedades Fetales/genética , Diagnóstico Prenatal , Cromosomas en Anillo , Tetrasomía/genética , Adulto , Centrómero/genética , Bandeo Cromosómico , Femenino , Enfermedades Fetales/diagnóstico , Feto/metabolismo , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Polimorfismo de Nucleótido Simple/genética , Embarazo
12.
Croat Med J ; 60(3): 273-283, 2019 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-31187956

RESUMEN

AIM: To assess the association between azoospermia factor c microrearrangements and semen quality, and between Y-chromosome background with distinct azoospermia factor c microrearrangements and semen quality impairment. METHODS: This retrospective study, carried out in the Research Center for Genetic Engineering and Biotechnology "Georgi D. Efremov," involved 486 men from different ethnic backgrounds referred for couple infertility from 2002-2017: 338 were azoospermic/oligozoospermic and 148 were normozoospermic. The azoospermia factor c microrearrangements were analyzed with sequence tagged site and sequence family variant markers, quantitative fluorescent polymerase chain reaction, and multiplex ligation probe amplification analysis. The Y-haplogroups of all participants were determined with direct single nucleotide polymorphism typing and indirect prediction with short tandem repeat markers. RESULTS: Our participants had two types of microdeletions: gr/gr and b2/b3; three microduplications: b2/b4, gr/gr, and b2/b3; and one complex rearrangement gr/gr deletion + b2/b4 duplication. Impaired semen quality was not associated with microrearrangements, but b2/b4 and gr/gr duplications were significantly associated with haplogroup R1a (P<0.001 and P=0.003, respectively) and b2/b3 deletions with haplogroup E (P=0.005). There were significantly more b2/b4 duplication carriers in Albanians than in Macedonians with haplogroup R1a (P=0.031). CONCLUSION: Even though azoospermia factor c partial deletions/duplications and Y-haplogroups were not associated with impaired semen quality, specific deletions/duplications were significantly associated with distinct haplogroups, implying that the Y chromosome background may confer susceptibility to azoospermia factor c microrearrangements.


Asunto(s)
Azoospermia/genética , Cromosomas Humanos Y , Oligospermia/genética , Análisis de Semen , Albania/etnología , Deleción Cromosómica , Duplicación Cromosómica , Reordenamiento Génico , Grecia/etnología , Haplotipos , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Estudios Retrospectivos
13.
BMC Med Genet ; 20(1): 108, 2019 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-31200655

RESUMEN

BACKGROUND: Split hand/foot malformation (SHFM) is a group of congenital skeletal disorders which may occur either as an isolated abnormality or in syndromic forms with extra-limb manifestations. Chromosomal micro-duplication or micro-triplication involving 17p13.3 region has been described as the most common cause of split hand/foot malformation with long bone deficiency (SHFLD) in several different Caucasian and Asian populations. Gene dosage effect of the extra copies of BHLHA9 gene at this locus has been implicated in the pathogenesis of SHFLD. CASE PRESENTATION: The proband was a female child born to non-consanguineous parents. She was referred for genetic evaluation of bilateral asymmetric ectrodactyly involving both hands and right foot along with right tibial hemimelia. The right foot had fixed clubfoot deformity with only 2 toes. The mother had bilateral ectrodactyly involving both hands, but the rest of the upper limbs and both lower limbs were normal. Neither of them had any other congenital malformations or neurodevelopmental abnormalities. Genetic testing for rearrangement of BHLHA9 gene by quantitative polymerase chain reaction confirmed the duplication of the BHLHA9 gene in both the proband and the mother. CONCLUSIONS: We report the first Sri Lankan family with genetic diagnosis of BHLHA9 duplication causing SHFLD. This report along with the previously reported cases corroborate the possible etiopathogenic role of BHLHA9 gene dosage imbalances in SHFM and SHFLD across different populations.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Duplicación de Gen , Deformidades Congénitas de las Extremidades/genética , Tibia/anomalías , Duplicación Cromosómica , Cromosomas Humanos Par 17/genética , Hibridación Genómica Comparativa , Ectromelia , Femenino , Deformidades Congénitas del Pie/genética , Dosificación de Gen , Reordenamiento Génico/genética , Estudios de Asociación Genética , Sitios Genéticos , Predisposición Genética a la Enfermedad , Deformidades Congénitas de la Mano/genética , Humanos , Recién Nacido , Deformidades Congénitas de las Extremidades/diagnóstico por imagen , Deformidades Congénitas de las Extremidades/fisiopatología , Tibia/diagnóstico por imagen , Tibia/fisiopatología
14.
Int J Biol Macromol ; 134: 316-329, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31078592

RESUMEN

Cysteine-rich receptor-like kinases (CRK) constitute one of the largest subfamily of receptor-like kinases, which play crucial roles in plant development and stress response. In total, 43, 37, 36, 38 and 170 CRK genes including duplicated genes were identified in the genome of Brachypodium distachyon, Hordeum vulgare, Oryza sativa, Sorghum bicolor and Triticum aestivum, respectively. These CRK proteins were tightly clustered into four phylogenetic groups and exhibited close syntenic relationship among orthologous genes. Majority of CRK proteins contain a transmembrane domain for plasma membrane localization. The organization of exon/intron, domains and motifs were variably conserved. Tissue-specific expression suggested the involvement of certain CRK genes in plant development. Modulated expression revealed their specific stress-responsive functions. Co-expression and interaction analysis indicated their role in signaling. Ks value and divergence time analysis suggested duplication of TaCRK genes before the hybridization of T. aestivum sub-genomes. Expression comparison of duplicated TaCRK genes revealed functional retention, neofunctionalization or pseudo-functionalization. Recombinant expression of a stress-responsive gene TaCRK68-A in Escherichia coli and Saccharomyces cerevisiae displayed enhanced tolerance against heat, drought, cold and salinity stresses. The study suggested vital functions of CRKs during development and stresses, and provides the basis for functional characterization of each gene in future studies.


Asunto(s)
Grano Comestible/enzimología , Grano Comestible/genética , Perfilación de la Expresión Génica , Genómica , Proteínas Quinasas/genética , Duplicación Cromosómica , Grano Comestible/fisiología , Filogenia , Estrés Fisiológico/genética , Sintenía
15.
Genes Chromosomes Cancer ; 58(10): 689-697, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30994215

RESUMEN

The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the new comprehensive cytogenetic scoring system for MDS, chromosome 7 anomalies are no longer generally assigned to poor risk features but are thoroughly separated. However, der(1;7)(q10;p10), hereinafter der(1;7), is merged into the group labeled "any other single" and belongs to the intermediate risk group, just by definition due to lack of adequate clinical data. The aim of our international collaborative was to clarify the "real" prognostic impact of der(1;7) on a homogenous and well-documented data base. We performed detailed analysis of 63 MDS patients with isolated der(1;7) constituting the largest cohort hitherto reported. Furthermore, clinical data are compared with those of patients with isolated del(7q) and isolated monosomy 7. Median overall survival (OS) of patients with der(1;7) is 26 months (hazard ratio (HR) 0.91 for del(7q) vs der(1;7) and 2.53 for monosomy 7 vs der(1;7)). The der(1;7) is associated with profound thrombocytopenia most probably causing the reduced OS which is in striking contrast to the low risk for AML transformation (HR 3.89 for del(7q) vs der(1;7) and 5.88 for monosomy 7 vs der(1;7)). Molecular karyotyping indicates that der(1;7) is generated in a single step during mitosis and that a chromosomal imbalance rather than a single disrupted gene accounts for malignancy. Thus, the current cytogenetic scoring system assigning isolated der(1;7) to the intermediate risk group is now confirmed by a sufficient data set.


Asunto(s)
Biomarcadores de Tumor/genética , Deleción Cromosómica , Duplicación Cromosómica , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 7/genética , Síndromes Mielodisplásicos/genética , Cariotipo Anormal , Adulto , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/patología , Análisis de Supervivencia
16.
Medicine (Baltimore) ; 98(15): e15146, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30985688

RESUMEN

To characterize the etiology underlying a novel case of global developmental delay syndrome (GDDS) identified in a female child, aged 3 years old. This syndrome is a common pediatric presentation estimated to affect 3.65% of children aged 3 to 17 years.The proband's detailed family history was used to infer a likely mode of inheritance for the GDDS. Genomic DNA samples collected from the proband and her parents were evaluated using conventional karyotyping, multiplex ligation-dependent probe amplification (MLPA), comparative genomic hybridization microarray (aCGH), and fluorescent in situ hybridization (FISH) analysis techniques.An analysis of the proband's family history suggested that she inherited the GDDS from her father. The conducted conventional karyotyping and MLPA methods failed to identify a causative defect for the GDDS; however, the aCGH analysis revealed both a 6.6-Mb deletion at p14-p15.3 of chromosome 10 (arr[hg19]; 100,026-6,710,183), and a 6.3-Mb duplication at p11.31-p11.32 of chromosome 18 (arr[hg19]; 136,226-6,406,733) in the proband. The conducted FISH analysis subsequently determined that these mutations resulted from a balanced translocation t(10;18)(p15.3; p11.32) carried by the proband's father. Finally, a bioinformatic analysis of the proband's mutations revealed ZMYND11 as a promising candidate causative gene for this case of GDDS.The present study demonstrates that the aCGH method can be used to effectively identify the location and approximate size of microdeletions and/or microduplications, but not balanced reciprocal translocations. The nonconventional analysis methods used in the present study may be applicable to other GDDS cases with elusive etiology, and likewise, ZMYND11 should be considered as a potential causative gene during the investigation of future GDDS cases.


Asunto(s)
Proteínas Portadoras/genética , Deleción Cromosómica , Duplicación Cromosómica , Discapacidades del Desarrollo/genética , Preescolar , Familia , Femenino , Humanos
17.
Gynecol Obstet Invest ; 84(4): 412-416, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30965333

RESUMEN

INTRODUCTION: X-linked recessive mutations predominantly affect male fetuses with milder or no abnormalities in female siblings. Most reports show only one affected member in the family. We are reporting a family affected with hydrocephalus, stenosis of the aqueduct of Sylvius, dysgenesis of the corpus callosum, and Xp22.33 microduplication. CASE PRESENTATION: Eighteen-year-old patient was evaluated for her 2 pregnancies; the first was a male fetus with severe hydrocephalus and the second a female fetus with mild hydrocephalus. Postnatal MRI evaluation of the male neonate revealed stenosis of the aqueduct of Sylvius, dysgenesis of the corpus callosum, and severe hydrocephalus requiring ventriculoperitoneal shunt. Postnatal MRI evaluation of the female neonate revealed mild hydrocephalus, stenosis of the aqueduct of Sylvius, and mild dysgenesis of the corpus callosum. The female baby did not require surgical intervention. Genetic testing of the mother and the 2 children revealed a 439 Kb duplication of Xp22.33. DISCUSSION: This family demonstrates typical X-linked recessive heritability. X-inactivation is a compensatory mechanism that explains the mild symptoms of the female child and the severe symptoms of the male child. This familial case shows the importance of prenatal testing and genetic counseling and testing, including karyotype and chromosomal microarray.


Asunto(s)
Agenesia del Cuerpo Calloso/genética , Duplicación Cromosómica/genética , Hidrocefalia/genética , Aberraciones Cromosómicas Sexuales , Adolescente , Agenesia del Cuerpo Calloso/patología , Acueducto del Mesencéfalo/patología , Constricción Patológica/genética , Femenino , Genes Recesivos/genética , Genes Ligados a X/genética , Humanos , Hidrocefalia/patología , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Mutación , Embarazo
18.
J Genet ; 982019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30945684

RESUMEN

Microduplications of the X chromosome are a rare cause of X-linked intellectual disability (XLID), a clinically and genetically heterogeneous spectrum of disorders. In the present study, a 950-kb Xp22.12 microduplication including the RPS6KA3 gene was detected in affected members of a family, including the proband (male), his mother and one maternal uncle. Four female carriers had major depression and one of them also had mild intellectual disability. The present and previous cases with overlapping microduplications suggest that Xp22.12 microduplications can be included in the neuropsychiatric copy number variations.


Asunto(s)
Cromosomas Humanos X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Discapacidad Intelectual/genética , Proteínas Quinasas S6 Ribosómicas 90-kDa/genética , Esquizofrenia/genética , Adulto , Duplicación Cromosómica , Variaciones en el Número de Copia de ADN , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Humanos , Discapacidad Intelectual/diagnóstico , Masculino , Persona de Mediana Edad , Linaje , Esquizofrenia/diagnóstico
19.
Cytogenet Genome Res ; 157(3): 141-147, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30947196

RESUMEN

Chromosomal microarray (CMA) is currently considered as a first-tier test in the genetic assessment of patients presenting with intellectual disability and/or multiple congenital abnormalities. The distinction between pathogenic CNVs, polymorphisms, and variants of unknown significance can be a diagnostic dilemma for cytogeneticists. The size of the CNV has been proposed as a useful criterion. We herein report the characterization of a 13.6-Mb interstitial duplication 20p11.1p12.1, found in a child presenting with mild global developmental delay, by standard karyotype and CMA. Unexpectedly, the same CNV was detected in the patient's mother and pregnant sister, who were healthy. On the basis of these results, an implication of this CNV in the neurological problems observed in the proband was considered to be unlikely. This report underlines the complexity of genetic counseling concerning rare chromosomal abnormalities, when little information is available either in the literature or in international cytogenetic databases.


Asunto(s)
Duplicación Cromosómica , Pintura Cromosómica/métodos , Anomalías Congénitas/genética , Discapacidad Intelectual/genética , Niño , Variaciones en el Número de Copia de ADN , Femenino , Asesoramiento Genético , Humanos , Masculino , Madres , Linaje , Hermanos
20.
Cell ; 176(6): 1310-1324.e10, 2019 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-30827684

RESUMEN

DNA rearrangements resulting in human genome structural variants (SVs) are caused by diverse mutational mechanisms. We used long- and short-read sequencing technologies to investigate end products of de novo chromosome 17p11.2 rearrangements and query the molecular mechanisms underlying both recurrent and non-recurrent events. Evidence for an increased rate of clustered single-nucleotide variant (SNV) mutation in cis with non-recurrent rearrangements was found. Indel and SNV formation are associated with both copy-number gains and losses of 17p11.2, occur up to ∼1 Mb away from the breakpoint junctions, and favor C > G transversion substitutions; results suggest that single-stranded DNA is formed during the genesis of the SV and provide compelling support for a microhomology-mediated break-induced replication (MMBIR) mechanism for SV formation. Our data show an additional mutational burden of MMBIR consisting of hypermutation confined to the locus and manifesting as SNVs and indels predominantly within genes.


Asunto(s)
Cromosomas Humanos Par 17 , Mutación , Anomalías Múltiples/genética , Puntos de Rotura del Cromosoma , Trastornos de los Cromosomas/genética , Duplicación Cromosómica/genética , Variaciones en el Número de Copia de ADN , Reparación del ADN/genética , Replicación del ADN , Reordenamiento Génico , Genoma Humano , Variación Estructural del Genoma , Humanos , Mutación INDEL , Modelos Genéticos , Polimorfismo de Nucleótido Simple , Recombinación Genética , Análisis de Secuencia de ADN/métodos , Síndrome de Smith-Magenis/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA