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Hereditary spastic paraplegias are clinically and genetically heterogeneous degenerative disorders, and pathological variants in the autosomal recessive ZFYVE26 gene are considered as very rare causes. We describe a novel mutation in ZFYVE26 gene found in a patient with autosomal recessive spastic paraplegias. The use of a 'target-gene' approach allowed us to expand the clinical spectrum associated with hereditary spastic paraplegias.

Spinal muscular atrophy (SMA) is an autosomal-recessive neuromuscular disorder characterized by motor neuron degeneration in the anterior horn of the spinal cord and brain stem, resulting in progressive muscle weakness and atrophy. The responsible survival motor neuron gene (SMN1; HGNC: 11117) is localized in 5q11.2-13.3. Screening for carriers of SMA is necessary for effective clinical/prenatal diagnosis and genetic counselling. In this study, the copy number of SMN1 gene was determined from a southern Italian population to estimate carrier frequency. This is the first report addressing the estimation of SMA carrier frequency in an Italian population. Our results show that the SMA carrier frequency in Sicily is higher than in the European populations and lower than in Mediterranean/Middle Eastern countries. The carrier testing could be a helpful tool for genetic counselling, to individuals with a positive family history. SMA is the second most common severe autosomalrecessive disorder after cystic fibrosis and the most frequent genetic cause of infant mortality, with an incidence of one per 6000–10,000 live births (Pearn 1980). Mutations in the survival motor neuron gene (SMN1; HGNC: 11117), localized in 5q11.2-13.3 within a large inverted duplicated element, cause SMA types I, II, III and IV (Lefebvre et al. 1995). Further, between 95% and 98% of individuals with recessive SMA have two deletion mutations (deletion of exons 7–8) and the remaining 2–5% have one deletion mutation (exons 7–8) and a second, different type of mutation (Ogino and Wilson 2002). People generally have between one and three copies of the SMN1 gene. Usually, people with two copies

Down’s syndrome (DS) is one of the most common numer- ical chromosomal aberrations, usually caused by trisomy of chromosome 21, and is frequently complicated with congen- ital heart defects, duodenal obs truction and other conditions including undescended testis (UDT) (Fonkalsrud 1970). The incidence of undescended testes in DS was reported to be 6.52% (Chew and Hutson 2004) while the incidence of UDT in the first year is approximately 0.2%–0.8% in the nor- mal population (Benson et al . 1991; Ichiyanagi et al . 1998). Rapley et al . (2000) provided evidence for a testicular germ- cell tumours (TGCT) predisposition locus at Xq27; the au- thors obtained an hlod score of 4.7 from families with at least one bilateral case, corresponding to a genome-wide signifi- cance level of P = 0 . 034. The proportion of families with undescended testis linked to this locus was 74%. SPANX (sperm protein associated with the nucleus in the X chro- mosome) gene family maps in the same chromosomal region and seven highly homologous genes belonging to this fam- ily have been described ( SPANX-A1, SPANX-A2, SPANX-B1, SPANX-B2, SPANX-C, SPANX-D and SPANX-E ) according to the human genome database build 36.2. These genes, made up of two exons separated by a small intron of ≈ 650 bp, are expressed in sperm cells (Westbrook et al . 2000) and in many tumours (Wang et al . 2003; Zendman et al . 2003; Westbrook et al . 2004). Moreover, expression of SPANX genes has been demonstrated in TGCT (Salemi et al . 2006). The function of SPANX gene-encoded proteins is currently unknown, and it is also not known if all the members or some of them are normally expressed in the testis (West- brook et al . 2000). Evidence suggests that CTp11 ,which is 100% homologous to SPANX-C , is expressed in tumours such as melanoma (Zendman et al . 2003), and SPANX-B in myeloma and other haematological malignancies (Wang et al . 2003; Zendman et al . 2003). SPANX-C mRNA was found expressed in normal tissues and in embryonal carcinomas of the testis (Salemi et al . 2006). Further, it is very di ffi cult to design primers adequate for gene-specific PCR amplification within the SPANX locus. For this reason, we decided to fo- cus our study on SPANX-C and SPANX-B genes. The aim of this study is to evaluate the genetic variability of SPANX-B and SPANX-C in D.UDT (Down’s syndrom patients a ff ected by undescended testis) compared with D (Down’s syndrom patients without undescended testis) and Nm (normal popu- lation).

In forensic science and in legal medicine Y chromosomal typing is indispensable for sex determination, for paternity testing in the absence of the father and for distinguishing males in multiple rape cases. Another potential application is the estimation of paternal geographic origin or family name from a crime stain to narrow down the range of suspects and thus reduce costs of mass screenings. However, Y typing alone cannot provide a sufficiently resolved DNA fingerprint as required for court convictions. Thus, there is a dilemma whether or not to sacrifice valuable material for the sake of extensive Y chromosomal investigations when stain DNA is limited (typically allowing only few PCR amplifications). We here describe a Y-chromosome-specific nucleotide insertion in the duplicate short tandem repeat (STR) locus DXYS156 which allows us to distinguish males from females as does the commonly used amelogenin system, but with the advantage that this locus is multi-allelic, thus substantially contributing towards DNA fingerprinting of a sample and furthermore enabling the detection of sample contamination. Yet another bonus is that both the X and the Y copies of DXYS156 have alleles specific to different parts of the world, offering separate estimates of maternal and paternal descent of that sample. We therefore recommend the inclusion of DXYS156 in standard multiplexing kits for forensic, archaeological and genealogical applications.

When the mtDNA profile of a crime scene matches that of a suspect, it is necessary to determine the probability of a chance match by consulting the frequencies of the identified allele in a "reference population". The ceiling principle suggests that that population should be chosen in which the allele of the suspect is found at the highest frequency, in order to give the suspect the maximum benefit of doubt. Recently, we advocated the use of a worldwide mitochondrial database combined with a geographical information system to identify the regions of the world with the highest frequencies of matching mtDNA types. Here, we demonstrate that the alternative approach of defining a ceiling reference population on the basis of continent or phenotype (race) is too coarse for a non-negligible percentage of mtDNA control region types.

The forensic application of mtDNA typing requires large databases which are regionally well defined. To further this aim, we have typed mtDNA in a sample of 111 French and 106 Sicilians. The French were typed for both hypervariable segments (HVR1 and HVR2) of the mtDNA control region, whereas the Sicilians were only typed for HVR1, but in addition for the coding region RFLP markers for mtDNA groups H, I, J, K, L, M, T, U, V and X. In both samples, the predominant sequence type by far was the Cambridge reference sequence. Comparing HVR1 sequences, we found that the French sample was twice as diverse as the Sicilian sample as measured by sequence matches. A further set of sequence match comparisons including the French, Sicilian, and the published British mtDNA samples, demonstrate that sequence matching probabilities within samples differ by less than a factor of 2 from the matching probabilities between samples.

Lack of association of HOXA1 and HOXB1 mutations and autism in Sicilian (Italian) patients

A consistent finding of many studies describing the spectrum of mutant phenylalanine hydroxylase (PAH) alleles underlying hyperphenylalaninemia is the impossibility of achieving a 100% mutation ascertainment rate using conventional gene-scanning methods. These methods include denaturing gradient gel electrophoresis (DGGE), denaturing high performance liquid chromatography (DHPLC), and direct sequencing. In recent years, it has been shown that a significant proportion of undetermined alleles consist of large deletions overlapping one or more exons. These deletions have been difficult to detect in compound heterozygotes using gene-scanning methods due to a masking effect of the non-deleted allele. To date, no systematic search has been carried out for such exon deletions in Italian patients with phenylketonuria or mild hyperphenylalaninemia. We used multiplex ligation- dependent probe amplification (MLPA), comparative multiplex dosage analysis (CMDA), and real-time PCR to search for both large deletions and duplications of the phenylalanine hydroxylase gene in Italian hyperphenylalaninemia patients. Four deletions removing different phenylalanine hydroxylase (PAH) gene exons were identified in 12 patients. Two of these deletions involving exons 4-5-6-7-8 (systematic name c.353-?_912 + ?del) and exon 6 (systematic name c.510-?_706 + ?del) have not been reported previously. In this study, we show that exon deletion of the PAH gene accounts for 1.7% of all mutant PAH alleles in Italian hyperphenylalaninemics.