Mucopolysaccharidosis type II: identification of 30 novel mutations among Latin American patients.

In this study, 103 unrelated South-American patients with mucopolysaccharidosis type II (MPS II) were investigated aiming at the identification of iduronate-2-sulfatase (IDS) disease causing mutations and the possibility of some insights on the genotype-phenotype correlation The strategy used for genotyping involved the identification of the previously reported inversion/disruption of the IDS gene by PCR and screening for other mutations by PCR/SSCP. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. By using this strategy, we were able to find the pathogenic mutation in all patients. Alterations such as inversion/disruption and partial/total deletions of the IDS gene were found in 20/103 (19%) patients. Small insertions/deletions/indels (<22 bp) and point mutations were identified in 83/103 (88%) patients, including 30 novel mutations; except for a higher frequency of small duplications in relation to small deletions, the frequencies of major and minor alterations found in our sample are in accordance with those described in the literature.

Pallister-Killian syndrome: tetrasomy of 12pter-->12p11.22 in a boy with an analphoid, inverted duplicated marker chromosome.

Supernumerary marker chromosomes (SMCs) without detectable alphoid DNA are predicted to have a neocentromere and have been referred to as mitotically stable neocentromere marker chromosomes (NMCs). Here we report the molecular cytogenetic characterization of a new case of Pallister-Killian syndrome (PKS) in a boy with an analphoid, inverted duplicated NMC derived from 12pter-->12p11.22 in his fibroblasts by using high-resolution comparative genetic hybridization (HR-CGH), multiplex fluorescent in situ hybridization (FISH) and bacterial artificial chromosome (BAC)-FISH mapping analyses with various alpha-satellite DNA probes, subtelomere probes and BAC-DNA probes. Precise identification of SMCs and NMCs is of essential importance in genetic counseling. HR-CGH is a more informative and often a faster way of precisely identifying the origin of SMCs. This case is the third report of PKS with an NMC containing an inverted duplication of partial 12p with available clinical data. These observations may help to determine the critical region for PKS and the mechanisms leading to the origin of the NMC derived from 12pter-->12p11.22 - a region that appears to be susceptible to the formation of neocentromeres. The use of subtelomeric probe PCP12p in buccal cells appears superior to the use of the centromere probe D12Z3 for the diagnosis of the PKS.

Characterization of an analphoid supernumerary marker chromosome derived from 15q25-->qter using high-resolution CGH and multiplex FISH analyses.

Supernumerary marker chromosomes (SMCs) without detectable alphoid DNA are predicted to have a neocentromere and have been referred to as mitotically stable neocentromere marker chromosomes (NMCs). We report the molecular cytogenetic characterization of a new case with analphoid NMC derived from 15q25-->qter using high-resolution comparative genomic hybridization (HR-CGH) and multiplex fluorescence in situ hybridization analyses with various alpha-satellite DNA probes, all-human-centromere probe (AHC), whole chromosome painting probes, and a subtelomere probe. The propositus is a dysmorphic infant who, at age 3 months, showed accelerated growth, partial deafness, and a phenotype similar to that of the eight previously reported cases of distal 15q tetrasomy. Chromosome studies showed that he had a de novo extra SMC in 80% of cells examined. HR-CGH revealed rev ish enh(15)(q25qter). Molecular cytogenetic analysis and molecular DNA polymorphism study demonstrated that this extra SMC is an NMC containing an inverted duplication of the distal long arm of chromosome 15 (tetrasomy 15q25-->qter) which originated paternally, i.e. ish der(15)(qte-->q25::q25[neocen]-->qter)(AHC-, CEP15-, WCP15+, PCP15q++). This case further elucidates the phenotype related to tetrasomy of this specific chromosome segment and represents a new report of a neocentromere on distal chromosome 15q suggesting that this region appears to be susceptible to the formation of neocentromeres.

Multiple anomalies possibly caused by a human homologue to the mouse disorganization (Ds) gene.

We describe a female infant with a combination of hamartomas and limb reduction anomalies, which might be caused by a human gene homologous to the mouse mutant disorganization (Ds) gene. The family history suggests a paternal uncle may also have been affected.

Paternal age as a risk factor for Down syndrome.

Although the effect of maternal age as a risk factor for Down syndrome (DS) is well known, the role of paternal age in the cause of DS has not been clearly established. To investigate this phenomenon we conducted a case-control study between July 1989 and February 1990. The cases were 318 children and teenagers with DS studied at the Specialized Educational Institutions of Lima City, Perú. They were paired with 1,196 control individuals that were selected from the birth records of 2 general hospitals of the city. For each case we tried to obtain 4 controls, paired by their date of birth, sex, and maternal age. The means of paternal age in the 2 groups were compared, first globally and then by groups of maternal age (< 21 years, 21-29 years, 30-34 years, 35-39 years and > 39 years). None of the comparisons gave a statistically significant difference between the 2 groups, using either the Student t-test or the Mann-Whitney U-test. The results obtained in this study give no evidence that paternal age can be considered a risk factor for the conception of a child with DS.

Trisomy 8: an additional case with unique manifestations [correction].

We report on an infant with multiple congenital anomalies and mosaic trisomy 8 [corrected]. Clinical findings are presented, and compared with those of the 24 cases previously reported. Some unusual characteristics found in this patient include macrocephaly, an extreme degree of palatal hypoplasia, and abnormally shaped long bones.

A new case of proximal 10q partial trisomy.

We report on a girl with mild phenotypic abnormalities and duplication of chromosome 10q11----10q22. The similarities to two previously reported cases with an identical chromosomal aberration provide further support for the delineation of this entity as a specific, clinically recognisable syndrome.

[Genealogic evidence of genetic control in Down syndrome]. / Evidencia genealógica de control genético en el síndrome de Down.

The aim of this work is to reevaluate the hypothesis of the existence of a possible genetic control of nondisjunction of chromosome 21. The population under study was the families trisomy (TLI) as diagnosed in the Medical Genetic Unit of LUZ from 1971 to 1988. The control population was the families of 418 individuals with no apparent genetic pathology (CON), approximately matched in age with the patients. The frequency of consanguineous unions in parents (UCPM), maternal grandparents (UCAM) and paternal grandparents (UCAP) of both patients and controls was determined. The results indicated that UCPM was significantly greater in TLI than CON while the UCAM and UCAP were more frequent in CON. The coefficient of consanguinity in parents of TLI was three times greater than in parents of CON. The results of this investigation suggest that the consanguinity should be considered another risk factor for the nondisjunction of chromosome 21 and it is independent of maternal age and support the hypothesis that there exists an autosomal recessive gene that, in the homologous state, results in a predisposition toward nondisjunction of chromosome 21 in the first mitotic division.

Double chromosome anomaly: interstitial deletion 5q and reciprocal translocation (1;11)(p22;q21).

We describe a girl with multiple congenital abnormalities and developmental delay; her karyotype showed an apparently balanced translocation between the short arm of chromosome 1 and the long arm of chromosome 11, and an interstitial deletion of the long arm of chromosome 5 (q15q31). The clinical findings are compared with those described in other cases of 5q deletion, and the origin of the chromosome rearrangements is briefly discussed.

Terminal deletion 4q in a severely retarded boy.

We report a boy with a de novo terminal deletion of chromosome 4q, (q31----qter) and compare him to 17 previously reported cases with the same anomaly. This case contributes further to the delineation of the del(4)(q31) phenotype, which seems to be clinically recognizable.