Another patient with 12q13 microduplication.

Interstitial duplication of the long arm of chromosome 12 is a rare cytogenetic condition. While several reports describe distal 12q duplication, only one case report of homogeneous, non-mosaic interstitial 12q13 duplication has been documented to date. The authors of that observation proposed that the associated phenotype represented a phenocopy of Wolf-Hirschhorn syndrome [Dallapiccola et al., 2009]. Only a few other recorded patients with deletion 12q13 → 12q21 involved mosaicism. We describe a new patient with homogeneous 12q13 duplication in a 6-year-old girl who, in early infancy, presented with dysmorphic features suggesting Wolf-Hirschhorn syndrome. What is potentially significant about this patient is that her facial phenotype evolved with age, suggesting a different gestalt in older patients.

Microarray application in prenatal diagnosis: a position statement from the cytogenetics working group of the Italian Society of Human Genetics (SIGU), November 2011.

A precise guideline establishing chromosomal microarray analysis (CMA) applications and platforms in the prenatal setting does not exist. The controversial question is whether CMA technologies can or should soon replace standard karyotyping in prenatal diagnostic practice. A review of the recent literature and survey of the knowledge and experience of all members of the Italian Society of Human Genetics (SIGU) Committee were carried out in order to propose recommendations for the use of CMA in prenatal testing. The analysis of datasets reported in the medical literature showed a considerable 6.4% incidence of pathogenic copy number variations (CNVs) in the group of pregnancies with sonographically detected fetal abnormalities and normal karyotype. The reported CNVs are likely to have a relevant role in terms of nosology for the fetus and in the assessment of reproductive risk for the couple. Estimation of the frequency of copy number variations of uncertain significance (VOUS) varied depending on the different CMA platforms used, ranging from 0-4%, obtained using targeted arrays, to 9-12%, obtained using high-resolution whole genome single nucleotide polymorphism (SNP) arrays. CMA analysis can be considered a second-tier diagnostic test to be used after standard karyotyping in selected groups of pregnancies, namely those with single (apparently isolated) or multiple ultrasound fetal abnormalities, those with chromosomal rearrangements, even if apparently balanced, and those with supernumerary marker chromosomes.

Association of syndromic mental retardation and autism with 22q11.2 duplication.

We describe a 5.3-year-old girl with autism, mental retardation, hypotonia, marked speech delay, and mild dysmorphic features with a 22q11.2 duplication. Her mother carries the same duplication and presents cleft palate, and normal intelligence. The clinical and behavioural phenotype of this relatively new syndrome is very heterogeneous, with high variability also in the familiar cases. Up till now, about 50 cases of 22q11.2 duplication have been reported, but only three of them are associated with autistic disorders. We propose that in addition to 22q13.3 deletion syndrome, also 22q11.2 duplication should be suspected in a patient with unspecified dysmorphisms, mental retardation, autism, hypotonia, and severe speech delay.

Identification of a novel mutation in the SRY gene in a 46, XY female patient.

BACKGROUND: The SRY gene encodes for a testis-specific transcription factor (TDF, testis determining factor) that plays a key role in sexual differentiation and development in males. Several SRY mutations have been described in patients with gonadal dysgenesis, accounting for 10-15% of the sex reversal cases. The reported mutations are both point mutations and deletions, mostly involving the high mobility group (HMG) box domain of SRY, which is a conserved region through the evolution, suggesting that SRY function strictly depends on the HMG box. CASE PRESENTATION: Here we describe the clinical, endocrinological and molecular data of a patient with complete 46, XY gonadal dysgenesis caused by SRY mutation located within the conserved HMG box. Using DNA direct sequencing of the SRY coding region, we identified a single nucleotide insertion at codon 89 with subsequent frameshift of the reading frame sequence, which results in a truncated protein as consequence of an introduction of a stop codon at the position 103. CONCLUSION: A novel SRY mutation has been described in a female with a gonadal dysgenesis associated with a 46, XY karyotype. The described case is of importance for genetic counseling.