Duplication of Yq- and proximal Yp-arms with deletion of almost all PAR1 (including SHOX) in a young man with non-obstructive azoospermia, short stature and skeletal defects.

Duplications of Yq arm (and AZF) seems to be tolerated by fertile males, while mutations, deletions, duplications or haploinsufficiency of SHOX can originate a wide range of phenotypes, including short stature and skeletal abnormalities. We report a case of non-obstructive azoospermia in a young man with short stature, skeletal anomalies, normal intelligence and hormonal parameters. This male showed a very singular Y-chromosome aberration, consisting of a duplication of Yq and proximal regions of Yp, with a deletion of almost all PAR1 in Yptel, including SHOX.

A case of polimalformed fetus with a microdeletion of CTNNA3 gene.

We report a case of a male fetus of 20 weeks of gestation with plurimalformed observed by transonic scan and confirmed by MR. The karyotype was 46, XY. Molecular analysis showed a microdeletion of about 100 kb in the CTNNA3 gene.

Congenital megaurethra in a fetus with Meckel syndrome and in a fetus with female pseudoermanphroditism. The first report of these occurrences.

Objective: the purpose of this paper is to report the first case of megaurethra in a fetus with Meckel syndrome and in a fetus with femal pseudoermaphroditism.

Results: the former case refers to a fetus of 13 weeks gestation with the three following prominent anomalies, observed by transonic scan and confirmed by autopsy: congenital megaurethra, anal atresia, single umbelical artery. The latter case refers to a fetus of 18 weeks gestation.

Severe myopia with unusual retinal anomalies and Dandy-Walker sequence in two sibs. A distinct new neuro-ocular disorder.

We have observed a male and a female, sibs of non-consanguineous parents, affected by severe myopia with characteristic retinal defects and Dandy-Walker variant. The peculiarity of the retinopathy consists of pathological myopia with anomalous vitreal fenestrated membranes in the retinal periphery. We suppose that these associations may configure a new genetic syndrome.

MRX87 family with Aristaless X dup24bp mutation and implication for polyAlanine expansions.

Background: Cognitive impairments are heterogeneous conditions, and it is estimated that 10% may be caused by a defect of mental function genes on the X chromosome. One of those genes is Aristaless related homeobox (ARX) encoding a polyA-rich homeobox transcription factor essential for cerebral patterning and its mutations cause different neurologic disorders. We reported on the clinical and genetic analysis of an Italian family with X-linked mental retardation (XLMR) and intra-familial heterogeneity, and provided insight into its molecular defect.

Heterozygosity mapping by quantitative fluorescent PCR reveals an interstitial deletion in Xq26.2-q28 associated with ovarian dysfunction.

Background: Deletions of Xq chromosome are reported for a number of familial conditions exhibiting premature ovarian failure (POF) and early menopause (EM).

Methods And Results: We describe the inheritance of an interstitial deletion of the long arm of the X chromosome associated with either POF or EM in the same family. Cytogenetic studies and heterozygosity mapping by quantitative fluorescent PCR revealed a 46,X,del(X)(q26.

Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5.

Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder that affects both the retina and vitreous body. Autosomal recessive FEVR was diagnosed in multiple individuals from three consanguineous families of European descent. A candidate-locus-directed genome scan shows linkage to the region on chromosome 11q flanked by markers D11S905 and D11S1314.

Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation.

X-linked nonspecific mental retardation (MRX) accounts for approximately 25% of mental retardation in males. A number of MRX loci have been mapped on the X chromosome, reflecting the complexity of gene action in central nervous system (CNS) specification and function. Eleven MRX genes have been identified, but many other causative loci remain to be refined to the single gene level.

A t(2;8) balanced translocation with breakpoints near the human HOXD complex causes mesomelic dysplasia and vertebral defects.

Mesomelic dysplasia is a severe shortening of forearms and forelegs, and is found in several distinct human syndromes. Here, we report the cloning of the breakpoints of a human t(2;8)(q31;p21) balanced translocation associated with mesomelic dysplasia of the upper limbs, as well as with vertebral defects. We show that this translocation does not disrupt any gene, hence it most likely exerts its deleterious effect by modifying gene regulation.

Identification of novel RP2 mutations in a subset of X-linked retinitis pigmentosa families and prediction of new domains.

X-linked Retinitis Pigmentosa (XLRP) shows a huge genetic heterogeneity with almost five distinct loci on the X chromosome. So far, only two XLRP genes have been identified, RPGR (or RP3) and RP2, being mutated in approximately 70% and 10% of the XLRP patients. Clinically there is no clearly significative difference between RP3 and RP2 phenotypes.

Mutation in the nerve-specific 5'non-coding region of Cx32 gene and absence of specific mRNA in a CMTX1 Italian family. Mutations in brief no. 195. Online.

Charcot-Marie-Tooth type I demyelinating neuropathies are genetically heterogeneous disorders (chrmosome 17,1,X). There are at least three genes on X chromosome, the more frequently involved being Cx32 in Xq13.1.

Two novel mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in X-linked retinitis pigmentosa (RP3). Mutations in brief no. 172. Online.

Recently a new gene called RPGR (retinitis pigmentosa GTPase regulator) was isolated in Xp21.1 and found to be mutated in patients with RP3 type X-linked retinitis pigmentosa. Two new mutations, the first a single base pair deletion and the other a two base pairs deletion, have been found in one Spanish and one Italian family.

Mutation analysis of the RPGR gene reveals novel mutations in south European patients with X-linked retinitis pigmentosa.

The RPGR (retinitis pigmentosa GTPase regulator) gene has been shown to be mutated in 10-20% of patients with X-linked retinitis pigmentosa (XLRP), a severe form of inherited progressive retinal degeneration. A total of 29 different RPGR mutations have been identified in northern European and United States patients. We have performed mutation analysis of the RPGR gene in a cohort of 49 southern European males affected with XLRP.

Autosomal recessive familial exudative vitreoretinopathy: evidence for genetic heterogeneity.

Two unrelated families with familial exudative vitreoretinopathy (FEVR) show apparent autosomal recessive inheritance rather than the previously reported autosomal dominant or X-linked recessive mode of inheritance. Compared with the other modes of inheritance, the inherited clinical features here include earlier onset (at birth) and a more severe progressive course.

The gene for mesomelic dysplasia Kantaputra type is mapped to chromosome 2q24-q32.

Mesomelic dysplasia Kantaputra type (MDK) (MIM *156232) is a new autosomal dominant skeletal dysplasia characterized by dwarfism, shortening of the forearms/lower-legs, carpal/tarsal synostosis, and dorsolateral foot deviation. We studied a Thai family in which 15 members in 3 generations were affected with MDK. With reference to the breakpoints of a balanced translocation [t(2;8)(q31;p21)] in patients from a previously reported Italian family with a skeletal dysplasia that appears similar to MDK, a linkage analysis was performed in the Thai family using 50 CA-repeat markers mapped to nearby regions (2q22-q34 and 8p24-p21) of the translocation breakpoints.

A further observation of corneal dystrophy and perceptive deafness in two siblings.

We studied two siblings with the rare association of corneal dystrophy and perceptive deafness (Harboyan syndrome). To our knowledge, this is the third description of this hereditary disorder. The results of the clinical, genetic, audiometric, and ocular examination of the two siblings and the type of inheritance, which agree with the previous description of the syndrome, are reported.

Linkage of DFNB1 to non-syndromic neurosensory autosomal-recessive deafness in Mediterranean families.

Recent studies show a susceptibility locus (DFNB1) responsible for non-syndromic neurosensory autosomal-recessive deafness (NSRD) mapping to the pericentromeric region of chromosome 13q. In order to better understand the frequency with which DFNB1 is the gene for deafness in our patient population and the role of DFNB1 in Caucasians, we performed a genetic linkage study with four microsatellite markers linked to DFNB1 in a total of 48 independent Mediterranean families, of which 30 and 18 were of Italian and Spanish descent, respectively. A maximum two-point lod score of 7.

Simultaneous occurrence of tetrasomy 21 and trisomy 8 in a patient with early blastic metamorphosis of chronic myeloproliferative disorder.

We report an unusual hyperdiploid karyotype characterized by the simultaneous occurrence of tetrasomy 21 and trisomy 8 detected during early blastic evolution of a BCR-ABL-negative chronic myeloproliferative disorder. Blast cells from this patient showed a striking response to all-trans-retinoic acid (ATRA)-induced differentiation as evaluated by CD15 expression following in vitro exposure to this inducer. Our report represents the first description of such a composite karyotype in human hematologic malignancies.

A clinical, genetic and echocardiographic study of hypertrophic cardiomyopathy in a large family.

Objectives: To confirm recent reports on the incidence of human lymphocyte antigens (HLA) in familial hypertrophic cardiomyopathy and to better define the genetic patterns found in these patients.

Methods: A large family (31 members, 18M, 13F, age range 6-80 years) with a high incidence of hypertrophic cardiomyopathy was screened for HLA, dermatoglyphic patterns and blood subtyping.

Results: Our finding show variable expression of the disease and reduced penetrance.

CFC syndrome: report on three additional cases.

We describe three patients, originating from three different Italian localities, affected by the cardio-facio-cutaneous (CFC) syndrome. In addition to a varying degree of mental retardation, these patients present characteristics consisting of a peculiar face with bitemporal frontal constriction and other anomalies involving the eyes, nose, ears, hair, skin, and heart that are consistent with this diagnosis.

Neu-Laxova syndrome: pathological, radiological, and prenatal findings in a stillborn female.

We describe a case of Neu-Laxova syndrome in a stillborn female. She was born at 41 weeks of gestation to consanguineous Italian parents, who had had 2 previous stillborn offspring. Pathological, radiological, and prenatal studies are reported.

A malformed girl with a de novo proximal 6q deletion.

An additional case of interstitial deletion of chromosome 6, the first with breakpoints in q12 and q14, is reported. The female infant was the malformed first child of young, healthy parents. A review of proximal 6q deletions is made.

Prenatal ultrasound diagnosis of macroglossia in the Wiedemann-Beckwith syndrome.

We report the ultrasound prenatal diagnosis at the 30th week of macroglossia in two sibs with the Wiedemann-Beckwith syndrome; the syndrome was also present in their mother. A study of high resolution chromosomes did not show any anomaly.