RESUMO
Deletions in the azoospermia factor region AZFa on the human Y chromosome and, more specifically, in the region that encompasses the ubiquitin-specific peptidase 9, Y-linked gene USP9Y have been implicated in infertility associated with oligospermia and azoospermia. We have characterized in detail a deletion in AZFa that results in an absence of USP9Y in a normospermic man and his brother and father. The association of this large deletion with normal fertility shows that USP9Y, hitherto considered a candidate gene for infertility and azoospermia, does not have a key role in male reproduction. These results suggest that it may not be necessary to consider USP9Y when screening the Y chromosome of infertile or subfertile men for microdeletions.
Assuntos
Deleção de Genes , Genes Ligados ao Cromossomo Y , Infertilidade Masculina/genética , Espermatogênese/genética , Ubiquitina Tiolesterase/genética , Adulto , Azoospermia/genética , Cromossomos Humanos Y , RNA Helicases DEAD-box/genética , Fertilidade/genética , Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Masculino , Microscopia Eletrônica de Transmissão , Antígenos de Histocompatibilidade Menor , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Contagem de Espermatozoides , Espermatozoides/ultraestruturaRESUMO
Partial or complete duplication of 5p is a rare chromosomal abnormality in which genotype-phenotype correlation studies are hampered by other commonly associated chromosomal abnormalities. We report on a new patient in whom a complete de novo trisomy 5p in all metaphases represented the only chromosomal aberration. The present case further contributes to delineate the typical clinical picture of the trisomy 5p syndrome. Long-term clinical follow-up demonstrated low levels of secretory immunoglobulin A (IgA) on several occasions and likely related to the patient's recurrent respiratory infections (RRIs), a main clinical feature of the trisomy 5p syndrome. An extensive neuroradiological study detected a progressive triventricular hydrocephalus during the fist year of life with subsequent stabilization. Neuronal migration disorders were also present and probably account for the drug-resistant epilepsy presented by the patient.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 5 , Hidrocefalia/genética , Encéfalo/patologia , Pré-Escolar , Feminino , Humanos , Hidrocefalia/patologia , Hibridização in Situ Fluorescente , Cariotipagem , Imageamento por Ressonância Magnética , Neurônios/patologia , SíndromeRESUMO
Pontocerebellar hypoplasia type 2 (PCH2) is a very rare autosomal recessive disorder. We report two unrelated female patients born to consanguineous parents presenting with this condition. Patient 1 showed a classical clinical/neuroradiological phenotype of PCH2 with dyskinesia/dystonia. Patient 2 had a neonatal onset of PCH2 with polyhydramnios, apneic spells, myoclonus, and an akinetic/rigidity condition. Neuroradiologically, patient 2 showed extensive pancerebral degeneration. Based on these observations, and in accordance with the published cases, two groups of PCH2 patients may be defined: (a) patients with dyskinesia/dystonia, severe hypoplasia of the infratentorial structures and less severe involvement of the supratentorial brain; and (b) patients with polyhydramnios, neonatal onset with tremulousness (hyperekplexia), no spontaneous activity, absence of dyskinesia and pancerebral degeneration. Finally, we report a dramatic positive response of the patient with dyskinesia/dystonia to levodopa treatment, and discuss the associated physiopathological implications.
Assuntos
Cerebelo/anormalidades , Cerebelo/patologia , Vias Neurais/anormalidades , Vias Neurais/patologia , Atrofias Olivopontocerebelares/patologia , Atrofias Olivopontocerebelares/fisiopatologia , Ponte/anormalidades , Ponte/patologia , Cerebelo/fisiopatologia , Criança , Pré-Escolar , Transtornos Cromossômicos/patologia , Transtornos Cromossômicos/fisiopatologia , Feminino , Genes Recessivos/genética , Humanos , Imageamento por Ressonância Magnética , Mutação/genética , Vias Neurais/fisiopatologia , Linhagem , Fenótipo , Ponte/fisiopatologia , Prosencéfalo/anormalidades , Prosencéfalo/patologia , Prosencéfalo/fisiopatologiaRESUMO
Schinzel-Giedion syndrome (SGS) is a rare disorder with a likely autosomal recessive pattern of inheritance which is characterized by several facial dysmorphisms, midface hypoplasia, multiple skeletal anomalies including short and sclerotic skull base, short neck, and post-axial polydactyly. Cardiac and urogenital malformations are also present. Thirty-three cases have been described so far. We report on a boy affected by SGS in whom a long-term EEG follow-up showed a progressive deterioration of the background bioelectric activity ending, at the age of 19 months, with a hypsarrhythmic pattern clinically correlated with severe and refractory infantile spasms. EEG deterioration and neuroradiological findings, which showed progressive brain atrophy, confirm the neurodegenerative nature of SGS. We also re-evaluated all the published cases and found that 33% of patients with SGS experienced neonatal seizures and another 25% developed West syndrome in the following months. The seizures appeared extremely refractory to several anticonvulsive treatments. In conclusion, we believe that SGS should be included among the causes of secondary West syndrome.
Assuntos
Anormalidades Múltiplas/fisiopatologia , Espasmos Infantis/etiologia , Anormalidades Múltiplas/diagnóstico , Anormalidades Craniofaciais/fisiopatologia , Eletroencefalografia , Cardiopatias Congênitas/fisiopatologia , Hirsutismo/fisiopatologia , Humanos , Recém-Nascido , Deficiência Intelectual/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Microcefalia/fisiopatologia , Convulsões/etiologia , Espasmos Infantis/fisiopatologia , SíndromeRESUMO
We report a patient with mental retardation, epilepsy, overgrowth, delayed bone age, peculiar facial features, corpus callosum hypoplasia, enlarged cisterna magna and right cerebellar hypoplasia. Array-CGH analysis revealed the presence of a de novo 3.2 Mb interstitial deletion of the long arm of chromosome 7 involving bands q22.2-q22.3. The rearrangement includes 15 genes and encompasses a genomic region that represents a site of frequent loss of heterozygosity in myeloid malignancies. Four genes are implicated in the control of cell cycle: SRPK2, MLL5, RINT1 and LHFPL3. Haploinsufficiency of these genes might therefore be associated with overgrowth and could confer susceptibility to cancers or other tumours, so that attention to this possibility would be appropriate during regular medical review. In conclusion, array-CGH analysis should be performed in patients with overgrowth where the known causes have already been excluded, because some still unclassified overgrowth syndromes may be caused by subtle genomic imbalances.