Assuntos
Leucemia Linfocítica Crônica de Células B , Mutação , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
We describe a 6-year-old boy with a de novo 12 Mb interstitial duplication of chromosome 17q11.1q12, identified by oligo array-CGH. The patient shows psychomotor developmental and language delay, dolicocephaly, minor facial anomalies, hypotonia and renal megacalicosis. The duplication involves the neurofibromatosis type I (NF1) gene and overlaps with long-range unusual deletions of the NF1 region, extending over 17q12 region and associated with renal cysts and diabetes (RCDA). To our knowledge this is the first case of a patient carrying a large-sized duplication involving the 17q11.2q12 region. In the duplicated chromosomal segment there are about 130 annotated genes. Among them, several genes which have been already proposed as candidate for mental retardation (MR) in patients with partially overlapping deletions may be responsible for neurological impairment in our patient. In addition, other genes within the duplicated region are of interest for possible correlation with a few clinical features of the patient.
Assuntos
Duplicação Cromossômica , Cromossomos Humanos Par 17/genética , Transtornos do Desenvolvimento da Linguagem/genética , Transtornos Psicomotores/genética , Criança , Hibridização Genômica Comparativa , Humanos , Deficiência Intelectual/genética , Masculino , Hipotonia Muscular/genética , Neurofibromatose 1/metabolismoRESUMO
The introduction of array-CGH analysis is allowing the identification of novel genomic disorders. However, this new high-resolution technique is also opening novel diagnostic challenges when inherited private CNVs of unclear clinical significance are found. Oligo array-CGH analysis of 84 patients with mild to severe mental retardation associated with multiple congenital anomalies revealed 10 private CNVs inherited from a healthy parent. Three were deletions (7q31, 14q21.1, Xq25) and seven duplications (12p11.22, 12q21.31, 13q31.1, 17q12, Xp22.31, Xq28) ranging between 0.1 and 3.8Mb. Six rearrangements were not polymorphic. Four overlapped polymorphic regions to the extent of 10-61%. In one case the size was different between the proband and the healthy relative. Three small rearrangements were gene deserts. The remaining seven had a mean gene content of five (ranging from 1 to 18). None of the rearranged genes is known to be imprinted. Three disease-genes were found in three different cases: KAL1 in dupXp22.31, STS in another dupXp22.31 and TCF2 in dup17q12. The patient carrying the last duplication presents sex reversal, Peters' anomaly and renal cysts and the duplication is located 4Mb away from the HSD17B1 gene, coding a key enzyme of testosterone biosynthesis. Considering the overlap with polymorphic regions, size-identity within the family, gene content, kind of rearrangement and size of rearrangement we suggest that at least in five cases the relationship to the phenotype has not to be excluded. We recommend to maintain caution when asserting that chromosomal abnormalities inherited from a healthy parent are benign. A more complex mechanism may in fact be involved, such as a concurrent variation in the other allele or in another chromosome that influences the phenotype.
Assuntos
Deleção de Genes , Duplicação Gênica , Deficiência Intelectual/genética , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Feminino , Heterozigoto , Humanos , Cariotipagem , Masculino , Hibridização de Ácido Nucleico , FenótipoRESUMO
The MURCS association [Müllerian Duct aplasia or hypoplasia (M), unilateral renal agenesis (UR) and cervicothoracic somite dysplasia (CS)] manifests itself as Müllerian Duct aplasia or hypoplasia, unilateral renal agenesis and cervicothoracic somite dysplasia. We report on a 22-year-old woman with bicornuate uterus, right renal agenesis, C2-C3 vertebral fusion (MURCS association) and 22q11.2 deletion. Angio-MRI revealed the aberrant origin of arch arteries. Hashimoto thyroiditis, micropolycystic ovaries with a dermoid cyst in the right ovary and mild osteoporosis were also diagnosed. Accurate revision of radiographs enabled us also to identify thoracolumbar and lumbosacral vertebral-differentiation defects. Audiometry and echocardiogram were normal. Bone densitometry showed osteoporosis. As per our evaluation, the patient had short stature, obesity (BMI 30.7) and facial features suggestive of the 22q11 deletion syndrome. Multiplex ligation-dependent probe amplification analysis showed a de-novo 22q11.2 deletion confirmed by array-comparative genomic hybridization analysis. We discuss whether this is a casual association or whether it is an additional syndrome owing to the well known phenotype extensive variability of the 22q11 deletion syndrome.