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1.
Am J Med Genet A ; 167A(4): 786-90, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25655674

RESUMO

The 10q26 deletion syndrome is a clinically heterogeneous disorder. The most common phenotypic characteristics include pre- and/or postnatal growth retardation, microcephaly, developmental delay/intellectual disability and a facial appearance consisting of a broad nasal bridge with a prominent nose, low-set malformed ears, strabismus, and a thin vermilion of the upper lip. In addition, limb and cardiac anomalies as well as urogenital anomalies are occasionally observed. In this report, we describe three unrelated females with 10q26 terminal deletions who shared clinical features of the syndrome, including urogenital defects. Cytogenetic studies showed an apparently de novo isolated deletion of the long arm of chromosome 10, with breakpoints in 10q26.1, and subsequent oligo array-CGH analysis confirmed the terminal location and defined the size of the overlapping deletions as ∼ 13.46, ∼ 9.31 and ∼ 9.17 Mb. We compared the phenotypic characteristics of the present patients with others reported to have isolated deletions and we suggest that small 10q26.2 terminal deletions may be associated with growth retardation, developmental delay/intellectual disability, craniofacial features and external genital anomalies whereas longer terminal deletions affecting the 10q26.12 and/or 10q26.13 regions may be responsible for renal/urinary tract anomalies. We propose that the haploinsufficiency of one or several genes located in the 10q26.12-q26.13 region may contribute to the renal or urinary tract pathogenesis and we highlight the importance of FGFR2 and probably of CTBP2 as candidate genes.


Assuntos
Deficiências da Aprendizagem/diagnóstico , Anormalidades Urogenitais/diagnóstico , Adolescente , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 10/genética , Hibridização Genômica Comparativa , Fácies , Feminino , Estudos de Associação Genética , Humanos , Deficiências da Aprendizagem/genética , Anormalidades Urogenitais/genética
2.
Genomics ; 103(4): 288-91, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24607569

RESUMO

Complex chromosome rearrangements (CCRs) are extremely rare in humans. About 20% of the apparently balanced CCRs have an abnormal phenotype and the degree of severity correlates with a higher number of breakpoints. Several studies using FISH and microarray technologies have shown that deletions in the breakpoints are common although duplications, insertions and inversions have also been detected. We report a patient with two simultaneous reciprocal translocations, t(3;4) and t(2;14;18), involving five chromosomes and six breakpoints. He showed dysmorphic features, preaxial polydactyly in the left hand, brachydactyly, postnatal growth retardation and developmental delay. The rearrangement was characterized by FISH analysis which detected an interstitial segment from chromosome 14 inserted in the derivative chromosome 2, and by whole genome array which revealed an interstitial deletion of approximately 4.5 Mb at the breakpoint site on chromosome 3. To our knowledge this microdeletion has not been previously reported and includes ~12 genes. The haploinsufficiency of one or several of these genes is likely to have contributed to the clinical phenotype of the patient.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 3 , Hibridização Genômica Comparativa/métodos , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 2 , Face/anormalidades , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Polidactilia/genética , Translocação Genética
3.
Am J Med Genet A ; 161A(9): 2369-75, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23894102

RESUMO

San Luis Valley syndrome, which is due to a recombinant chromosome 8 (SLV Rec8) found in Hispanic individuals from Southwestern United States, is a well-established syndrome associated with intellectual disabilities and, frequently, severe cardiac anomalies. We report for the first time on a Moroccan girl with a recombinant chromosome 8 prenatally diagnosed as SLV Rec8 by conventional cytogenetic studies. At birth, an oligo array-CGH (105 K) defined the breakpoints and the size of the imbalanced segments, with a deletion of ≈ 2.27 Mb (8p23.2-pter) and a duplication of ≈ 41.93 Mb (8q22.3-qter); thus this recombinant chromosome 8 differed from that previously reported in SLV Rec8 syndrome. The phenotypic characteristics associated with this SLV Rec8 genotype overlap those commonly found in patients with 8q duplication reported in the literature. We review SLV Rec8 and other chromosome 8 aberrations and suggest that the overexpression of cardiogenic genes located at 8q may be the cause of the cardiac defects in this patient.


Assuntos
Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Duplicação Cromossômica , Inversão Cromossômica , Recombinação Genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Adulto , Bandeamento Cromossômico , Cromossomos Humanos Par 8/genética , Hibridização Genômica Comparativa , Fácies , Feminino , Humanos , Hibridização in Situ Fluorescente , Fenótipo , Gravidez , Diagnóstico Pré-Natal
4.
Artigo em Inglês | MEDLINE | ID: mdl-37559368

RESUMO

One-month old breastfeeding infant, full-term birth, with normal anthropometric measurements at birth is referred to Pediatric Nephrology due to a nephrocalcinosis. The patient presents dysmorphic features and heart disease. A metabolic study is conducted on blood and urine yielding results within normal parameters, except for renal concentration test and acidification test. At 6 months of age, patient presents overgrowth, which along with other clinical signs arouse suspicion of Sotos Syndrome. Molecular genetic testing detects heterozygous deletion in 5q35 between bands q35.2 and q35.3, affecting genes NSD1, SLC34A1 and FGFR4, which is compatible with this syndrome and with nephrocalcinosis as a rare association.

5.
Am J Med Genet A ; 152A(10): 2670-80, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20799321

RESUMO

We report on newborn baby with microcephaly, facial anomalies, congenital heart defects, hypotonia, wrist contractures, long fingers, adducted thumbs, and club feet. Cytogenetic studies revealed an inverted duplication with terminal deletion (inv dup del) of 2q in the patient and a paternal 2qter deletion polymorphism. Microsatellite markers demonstrated that the inv dup del was maternal in origin and intrachromosomal. Intra or interchromosomal rearrangements may cause this aberration either by a U-type exchange (end-to-end fusion), an unequal crossover between inverted repeats (non-allelic homologous recombination: NAHR), or through breakage-fusion-bridge (BFB) cycles leading to a sister chromatid fusion by non-homologous end joining (NHEJ). A high-resolution oligo array-CGH (244 K) defined the breakpoints and did not detect a single copy region with a size exceeding 12.93 Kb in the fusion site. The size of the duplicated segment was 38.75 Mb, extending from 2q33.1 to 2q37.3 and the size of the terminal deletion was 2.85 Mb in 2q37.3. Our results indicate that the inv dup del (2q) is likely a non-recurrent chromosomal rearrangement generated by a NHEJ mechanism. The major clinical characteristics associated with this 2q rearrangement overlap with those commonly found in patients with 2q duplication reported in the literature.


Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Inversão Cromossômica , Cromossomos Humanos Par 2 , Rearranjo Gênico , Duplicações Segmentares Genômicas , Bandeamento Cromossômico , Hibridização Genômica Comparativa , Pai , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Masculino , Mães , Análise de Sequência com Séries de Oligonucleotídeos
6.
Am J Med Genet A ; 149A(11): 2513-21, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19842199

RESUMO

Two syndromes with abnormalities of the short arm of chromosome 5 have been described: cri-du-chat (resulting from 5p deletion) and trisomy 5p. We report for the first time a patient with both syndromes, resulting from a complex chromosomal rearrangement with an inverted duplication of 5p13.1-p14.2, a deletion of 5p14.2-pter, and a duplication of 5p12, characterized by array-CGH and BAC clones. The patient showed phenotypic characteristics of both syndromes and died at 3 months of age as a result of cardiorespiratory failure, probably associated with the clinical severity of the trisomy 5p syndrome. We propose a potential causative mechanism for this rearrangement.


Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 5/genética , Síndrome de Cri-du-Chat/genética , Trissomia/genética , Adulto , Bandeamento Cromossômico , Cromossomos Artificiais Bacterianos/genética , Evolução Fatal , Feminino , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Masculino , Meiose , Fenótipo , Gravidez , Síndrome
7.
Gene ; 497(2): 292-7, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22342398

RESUMO

Rapp-Hodgkin Syndrome (RHS) is a genetic disorder resulting from mutations in the TP63 gene encoding p63 transcription factor. p63 is directly associated with a cis-regulatory element on chromosome 7q21 that controls the expression of DLX5 and DLX6 genes which are involved in craniofacial abnormalities and ectrodactyly or split hand/foot malformation (SHFM). Chromosomal deletions on 7q21 locus can result in loss of DXL5/DLX6 and/or in loss/disruption of cis-regulatory elements, at which p63 binds. We report two patients that have in common a p63-Dlx5/Dlx6 pathway dysregulation. One showed growth retardation, craniofacial dysmorphism, syndactyly, developmental delay and a de novo deletion (~8.5Mb) on chromosome 7q21.13-q21.3, including DLX5 and DLX6. The second patient with a clinical diagnosis of RHS showed a de novo heterozygous missense mutation, c. 401G>A (p.G134D), in TP63 (exon 4). Our findings may contribute to a greater understanding of the pathogenic mechanisms underlying disorders caused by TP63 mutations.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Displasia Ectodérmica/genética , Proteínas de Homeodomínio/genética , Complexo de Endopeptidases do Proteassoma/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Fenda Labial/metabolismo , Fissura Palatina/metabolismo , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/metabolismo , Displasia Ectodérmica/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Lactente , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/metabolismo , Masculino , Mutação de Sentido Incorreto/genética , Deleção de Sequência/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
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