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Introduction: Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are allelic and caused by mutations in the COMP gene. Other mutations in the genes MMP13, AIFM1, B3GALT6, MATN3, COL9A1, COL9A2, COL9A3, and SLC26A2 have also been associated with evidence of dysplasia in the epiphysis, metaphysis, and spine. Case Presentation: We report on the first Mexican patient diagnosed with PSACH. The diagnosis was confirmed by identifying a recurrent heterozygous mutation c.2153G>C (p.Arg718Pro) in the COMP gene using whole-exome sequencing. Discussion: The anterior spindle-shaped vertebral bodies and severe short stature are not observed in patients carrying p.Arg718Pro, identifying another amino acid site associated with clinical heterogeneity. Reporting new cases with clinical heterogeneity in terms of phenotype plays a crucial role in understanding PSACH and MED pathogenesis. The most important aspect of this presentation is providing a new perspective on a recognized clinical scenario, thus setting the standard for better genetic counseling.

The proband in this study was a 16-year-old Mexican girl with psychotic and dyskinetic symptoms, and brain MRI showed at the basal ganglia the 'eye-of-the-tiger' sign. DNA direct sequencing identified a novel compound heterozygous mutation in the PANK2 gene. The diagnosis of pantothenate kinase-associated neurodegeneration (PKAN) disorder was made. This novel change increases the pool of PANK2 mutations. It supports the published data suggesting that PANK2 plays a significant role in patients expressing psychiatric phenotypes in the PKAN syndrome. When a patient presents with dyskinesia and psychiatric symptoms, PANK2 should be investigated as a possible diagnosis, and genetic consultation should be recommended.

Individuals with 3p deletion show a great clinical variability. Apparently, a 1.5-Mb terminal deletion, including the CRBN and CNTN4 genes, is sufficient to cause this syndrome. Partial trisomy 13q is a rare chromosomal abnormality with a variable phenotypic expression, but in most cases, patients have a phenotype resembling complete trisomy 13. The aim of the present study is to describe a 9-month-old Mexican male patient with 3p deletion/13q duplication and a novel clinical finding. He presented with facial dysmorphism and multiple congenital alterations. Echocardiogram revealed cardiac insufficiency with hypertrophic cardiomyopathy and pulmonary hypertension, not previously reported. Karyotype from the patient and his father were 46,XY,add(3)(p26) and 46,XY,t(3;13), respectively. Microarray assay of the proband exhibited an approximately 2.6-Mb loss at terminal 3p26.3 and a 27.7-Mb gain of the long arm in terminal chromosome 13 at q31.1q34. A chromosomal imbalance with a partial trisomy 13q31.1q34 and monosomy 3p26.3 of paternal origin were detected. Microarray assay of both parents were normal. The proband has a cardiomyopathy not previously reported. These data enrich the spectrum of clinical manifestations in 3p deletion/3q duplication chromosomopathy.

BACKGROUND We described the main features of an infant diagnosed with facial dysmorphic, language failure, intellectual disability and congenital malformations to strengthen our understanding of the disease. Currently, treatment is only rehabilitation and surgery for cleft lip and palate. CASE SUMMARY The proband was a 2-years-8-months-old girl. Familial history was negative for congenital malformations or intellectual disability. The patient had microcephaly, upward-slanting palpebral fissures, depressed nasal bridge, bulbous nose and bilateral cleft lip and palate. Brain magnetic resonance imaging showed cortical atrophy and band heterotopia. Her motor and intellectual development is delayed. A submicroscopic deletion in 11p13 involving the elongator acetyltransferase complex subunit 4 gene (ELP4) and a loss of heterozygosity in Xq25-q26.3 were detected. CONCLUSION There is no treatment for the ELP4 deletion caused by a submicroscopic 11p3 deletion. We describe a second case of deletion of the ELP4 gene without aniridia, which confirms the association between ELP4 gene with several defects and absence of this ocular defect. Additional clinical data in the deletion of the ELP4 gene as cleft palate, facial dysmorphism, and changes at level brain could be associated to this gene or be part of the effect of the recessives genes involved in the loss of heterozygosity region of Xq25-26.3.

Anterior segment dysgenesis (ASD) and Axenfeld-Rieger spectrum (ARS) are mainly due to PITX2 and FOXC1 defects, but it is difficult in some patients to differentiate among PITX2-, FOXC1-, PAX6- and CYP1B1-related disorders. Here, we set out to characterize the pathogenic variants (PV) in PITX2, FOXC1, CYP1B1 and PAX6 in nine unrelated Mexican ARS/ASD patients and in their available affected/unaffected relatives.Automated Sanger sequencing of PITX2, FOXC1, PAX6 and CYP1B1 was performed; those patients without a PV were subsequently analyzed by Multiplex Ligation-dependent Probe Amplification (MLPA) for PITX2, FOXC1 and PAX6. Missense variants were evaluated with the MutPred, Provean, PMUT, SIFT, PolyPhen-2, CUPSAT and HOPE programs.We identified three novel PV in PITX2 (NM_153427.2:c.217GA, c.233TC and c.279del) and two in FOXC1 [NM_001453.2:c.274CT (novel) and c.454TA] in five ARS patients. The previously reported FOXC1 c.367CT or p.(Gln123*) variant was identified in a patient with ASD. The ocular phenotype related to FOXC1 included aniridia, corneal opacity and early onset glaucoma, while an asymmetric ocular phenotype and aniridia were associated with PITX2. No gene rearrangements were documented by MLPA analysis, nor were any PV identified in PAX6 or CYP1B1.Heterozygous PV in the PITX2 and FOXC1 genes accounted for 66% (6/9) of the ARS/ASD cases. The absence of PAX6 or CYP1B1 abnormalities could reflect our small sample size, although their analysis could be justified in ARS/ASD patients that present with congenital glaucoma or aniridia.

Background Sensorineural hearing loss (SNHL) is a clinically and genetically heterogeneous disease. In some populations, c.365delG mutation in the GJB2 gene represents the most frequent cause of hereditary SNHL. The great diversity of mutations in the GJB2 gene worldwide highlights the participation of ethnic background in SNHL. Objective To describe the presence of homozygous c.del35G mutation in the GJB2 gene in a Mexican family with SNHL. Materials and methods A Mexican family with SNHL was included in the study. Analysis of the GJB2 gene was performed through whole exome sequencing (WES) and DNA direct sequencing analysis in all members of the family and in 100 normal controls Results Affected sibs showed the homozygous c.del35G mutation in the GJB2 gene. Parents of the families were heterozygous for the molecular defect and had normal audition. Conclusion We describe a homozygous c.del35G mutation in the GJB2 gene through WES analysis, a homozygous mutation with a very low occurrence in Mexican population.

Background Cytochrome P450 2C9 (CYP2C9) is an important enzyme in the metabolism of many drugs, including NSAIDs, antidepressants and anticoagulants. In vitro and in vivo studies have demonstrated that CYP2C9 polymorphisms modify the activity of the enzyme and subsequently the metabolism of different drugs. Objective To characterize the diclofenac pharmacokinetics in healthy subjects with the wild type form of CYP2C9 genotype. Methods Twenty five healthy women were included in the study; a single dose of diclofenac (50 mg) was administered orally. Pharmacokinetic analyses at 12 different times were performed. DNA was extracted from peripheral blood and analyzed through direct sequencing. The CYP2C9*1/*1 allele was found in all subjects. Using the AUC 0-inf parameter, we classified the 25 volunteers as poor, intermediate and extensive metabolizer (2285.421/3217.442/4637.450, respectively). We detected statistical significant differences between the groups, especially between poor metabolizers versus intermediate and extensive metabolizers. Conclusions This data indicate that CYP2C9 is not the only enzyme responsible of the metabolism of diclofenac, so it is important to analyze other cytochromes and their variants potentially involved in the metabolism of this drug.

Craniofrontonasal syndrome (CFNS) is a rare genetic entity with X-linked dominant inheritance. CFNS is due to mutations in the Ephrin-B1 (EFNB1) gene. It is characterized by brachycephaly, frontonasal dysplasia, palate/lip defects, dental malocclusion, short neck, split nails, syndactyly, toe and finger defects, and minor skeletal defects. Intelligence is usually unaffected. CFNS exhibits unexpected manifestations between males and females as the latter are more affected. Cellular or metabolic interference due to X inactivation explains the more severe phenotype in heterozygous females. One family with several members affected with CFNS and 100 healthy controls were examined. DNA from leukocytes was isolated to analyze the EFNB1 gene. We did molecular modeling to assess the impact of the mutation on the EFNB1-encoded protein. DNA sequencing analysis of the EFNB1 gene of the affected members showed the heterozygous missense mutation c.451G>A in the EFNB1 gene (GRcH38, chrX: 68,839,708; GERP score in hg38 of 9.961). This transition mutation resulted in the substitution of Gly at position 151 by Ser. Analysis of the healthy members of the family and 100 unrelated controls showed a normal sequence of the EFNB1 gene. Phenotypes of the patients in this family differ from the classical CFNS due to the decreased size of sulci and fissures, subarachnoid space and ventricles, and the absence of a cleft lip/palate.

Congenital cataract, an important cause of reversible blindness, is due to several causes including Mendelian inheritance. Thirty percent of cataracts are hereditary with participation of the gamma crystallin genes. Clinical and genetic heterogeneity is observed in patients with gene mutations and congenital cataract; about 40 genetic loci have been associated with hereditary cataract. In this study, we identified the underlying genetic cause of an autosomal dominant pulverulent cataract (ADPC) in a large Mexican family. Twenty-one affected patients and 20 healthy members of a family with ADPC were included. Genomic DNA was analyzed by whole exome sequencing in the proband, a normal daughter, and in an affected son, whereas DNA Sanger sequencing was performed in all members of the family. After the bioinformatics analysis, all samples were genotyped using Sanger sequencing to eliminate variants that do not cosegregate with the cataract. We observed a perfect cosegregation of a nonsense mutation c.475C>T (p.Q155*) in exon 6 of the CRYBB2 gene with ADPC. We calculated a logarithm of the odds score of 5.5. This mutation was not detected in healthy members of the family and in 100 normal controls. This is the first Mexican family with ADPC associated with a p.Q155* mutation. Interestingly, this specific mutation in the CRYBB2 gene seems to be exclusively associated with pulverulent/cerulean cataract (with some clinical variability) independent of the population's genetic background.

The aim of this study was to describe a case of severe keratitis-ichthyosis-deafness (KID) syndrome with ocular surface squamous neoplasia.The affected patient underwent complete ocular and systemic examinations. The molecular studies included polymerase chain reaction amplification and automated DNA sequencing of the complete gap junction beta-2 (GJB2) gene coding sequence.A 30-year-old man presented with generalized erythro-hyperkeratosis and deafness and complaints of decreased visual acuity, tearing, and photophobia. Ophthalmic examination showed corneal erosion, vascularization, and a gray gelatinous lesion partially covering the right cornea, suggestive of squamous neoplasia. The clinical features were characteristic of KID syndrome. This diagnosis was confirmed with a DNA analysis showing the pathogenic variant p.D50N in the GJB2 gene. Presumed squamous neoplasia was treated with topical interferon α2b.KID syndrome is a very rare disease that has been reported with an incremental incidence of squamous cell carcinoma of the mucous membranes and skin (12%-15%). Here, we presented a case of severe systemic KID syndrome with ocular surface squamous neoplasia.

The proband in this study was a 4-year-old Mexican girl with Blau syndrome. She and her affected family members had skin rash and arthritis but no uveitis. Exome sequencing and DNA direct sequencing from blood samples revealed a novel nucleotide-binding oligomerization domain-containing protein 2 gene mutation in the affected family members. This study is the first report of a Mexican family with Blau syndrome showing good infliximab treatment response. The novel mutation in the nucleotide-binding oligomerization domain-containing protein 2 gene (c.1808A>G) enriches the mutation spectrum in Blau syndrome. This family represents one of the few cases of autosomal Blau syndrome with no uveitis; because of phenotype variability, it is important to recognize Blau syndrome's clinical spectrum and recommend genetic consultation.

Rearrangements of the distal region of 9p are important chromosome imbalances in human beings. Trisomy 9p is the fourth most frequent chromosome anomaly and is a clinically recognizable syndrome. Kleefstra syndrome, previously named 9q subtelomeric deletion syndrome, is either caused by a submicroscopic deletion in 9q34.3 or an intragenic mutation of EHMT1. We report a Mexican male patient with abnormal development, dysmorphism, systemic anomalies and a complex chromosomal rearrangement (CCR). GTG-banding revealed a 46,XY,add(9)(q34.3) karyotype, whereas array analysis resulted in arr[hg19] 9p24.3p23(203,861-11,842,172)×3, 9q34.3(138,959,881-139,753,294)×3, 9q34.3(139,784,913-141,020,389)×1. Array and karyotype analyses were normal in both parents. Partial duplication of 9p is one of the most commonly detected autosomal structural abnormalities in liveborn infants. A microdeletion in 9q34.3 corresponds to Kleefstra syndrome, whereas a microduplication in 9q34.3 shows a great clinical variability. Here, we present a CCR in a patient with multiple congenital anomalies who represents the first case with partial 9p trisomy, partial 9q trisomy and partial 9q monosomy.

Background Hereditary sensorineural hearing loss (SNHL) is a genetically heterogeneous disorder worldwide. Mutations in the GJB2 gene are a frequent cause of hereditary SNHL. There is a prevalence of certain mutations in various populations which suggests that specific mutations may be influenced by ethnic background. Objective To analyze the prevalence of GJB2 , GJB6 mutations in several geographic areas of Mexico in patients with hereditary SNHL. Materials and methods One hundred and forty Mexican unrelated propositi with prelingual SNHL were included in the study. All patients had three previous generations born in Mexico and belonged to no specific ethnic group. Analyses of the GJB2 and GJB6 genes and mt.1555A Results Twenty-three homozygous mutations, 57 heterozygous mutations, 1 double heterozygous ( GJB2 / GJB6 ) and 59 wild-type genotypes in the GJB2 gene were observed. Three patients had the homozygous c.del35 mutation whereas 26 patients were heterozygous for this gene defect. Only one patient with the GJB6 gene deletion was present (it includes the double heterozygous GJB2 / GJB6 ). The mt.1555A > G mutation was not detected. Conclusion We found a great variety of mutations depending on the analyzed region in patients with SNHL; 57.86% of patients had affection in one or two alleles in GJB2 or GJB6 genes whereas 42.14% were wild-type. In some cases, allele distribution depended on region. Molecular studies of more genes involved in hereditary non-syndromic SNHL are required to completely confirm the molecular basis of hearing loss in Mexican population.

Microdeletions of the long arm of chromosome 13 lead to a characteristic facial appearance with systemic affection; 13q deletion shows a wide phenotypic spectrum that varies with respect to the location and size of the deletion region. The main clinical features are mental retardation, growth retardation, craniofacial dysmorphy and various congenital defects. In the present study we describe the case of an adult female of Mexican origin with microcephaly, facial dysmorphism, short stature, hand anomalies and normal intelligence associated with a de novo 13q31.3-q32.1 microdeletion that involved several genes including the MIR17HG and the GPC5 genes.

Complete monosomy mosaic of chromosome 21 is a rare disorder. The syndromic features are highly variable. This study describes a girl of Mexican origin with complete monosomy 21 in mosaicism with novel findings, including cortical atrophy, macrostomia, pectum excavatum and immune deficiencies. Parental karyotypes were normal. FISH analysis with probes from 21q22.1-q22.2 region and centromere of X DNA probe was performed on peripheral blood lymphocytes whereas 21q22.1-q22.2 and 21q, 4p, 4q subtelomeric DNA probes were tested in fibroblasts. We propose that the monosomy 21 mosaicism is the cause of the survival of children with more than 4 months of age.

Background Autosomal dominant tricho-rhino-phalangeal syndrome I (TRPS I) is due to mutations in the TRPS1 gene. Tricho-rhino-phalangeal syndrome I is characterized by peculiar face and skeletal anomalies. Cone-shaped epiphyses are the characteristic radiographic findings. Objective To describe 2 families with TRPS I and 2 novel mutations in the TRPS1 gene. Patients The study included 2 nonrelated families with TRPS I. All exons of the TRPS1 gene were analyzed from genomic DNA. Results The TRPS1 gene mutation analysis showed in family 1 the c.978C>A nonsense mutation within exon 4 and in family 2 the c.164A>C missense mutation within exon 3. Conclusions We found 2 families with TRPS1 caused by 2 novel mutations in the TRPS gene, particularly a missense mutation in exon 3, outside the GATA zinc finger domain, that leads a mild TRPS phenotype. Our data show a higher genotypic spectrum in the TRPS I and demonstrate that mutations in the amino terminus of the transcription factor result in TRPS I syndrome.

Background Pycnodysostosis, an autosomal recessive skeletal dysplasia, is characterized by short stature, osteosclerosis, delayed cranial suture closure, hypoplastic mandible, acro-osteolysis, hypoplastic clavicle, and dental anomalies. The disorder is caused by CTSK gene defects, a gene localized on 1q21. Purpose To describe the clinical, radiological, and molecular findings in a family with pycnodysostosis. Methods The CTSK gene was analyzed from genomic DNA in a nonconsanguinity Mexican family with 3 affected members with pycnodysostosis and 100 healthy controls. Results and Interpretation We identified the novel homozygous mutation c.908G>A within exon 8 of the CTSK gene. This missense mutation leads to the substitution of the amino acid glycine at position 303 by glutamic acid (G303E) in cathepsin K protease. No genotype/phenotype correlation was present in affected members of the family with pycnodysostosis.

Jacobsen syndrome (JBS) is an uncommon contiguous gene syndrome. About 85-92% of cases have a de novo origin. Clinical variability and severity probably depend on the size of the affected region. The typical clinical features in JBS include intellectual disability, growth retardation, craniofacial dysmorphism as well as craniosynostosis, congenital heart disease, and platelet abnormalities. The proband was a 1 year/3-month-old Mexican male. Oligonucleotide-SNP array analysis using the GeneChip Human Cytoscan HD was carried out for the patient from genomic DNA. The SNP array showed a 14.2-Mb deletion in chromosome 11q23.3q25 (120,706-134,938 Mb), which involved 163 RefSeq genes in the database of genomic variation. We report a novel deletion in JBS that increases the knowledge of the variability in the mutation sites in this region and expands the spectrum of molecular and clinical defects in this syndrome.

Background: Mutations and polymorphisms have been identified in the CYP1B1 gene; while mutations that affect the conserved core structures of cytochrome P4501B1 result in primary congenital glaucoma (PCG), mutations in other regions hold the potential to define differences in estrogen metabolism. In the present study, we analyzed the CYP1B1 gene in Mexican patients with PCG and described four novel mutations. Materials and Methods: The sample included 12 nonrelated cases with PCG. Analysis of coding regions of the CYP1B1 gene was performed through PCR and DNA sequencing analysis from genomic DNA. Results and Discussion: Molecular analysis of the CYP1B1 gene showed the following molecular defects: (1) a novel single-base pair deletion within codon 370 (1454delC) that produces a substitution of leucine instead of proline and a premature stop codon 57 amino acids after the last original amino acid; this family also harbored a novel polymorphic variant of the cytochrome P4501B1 with six single-nucleotide polymorphisms (142C→G; 355G→T; 729G→C; 4326C→G; 4360C→G and 4379C→T); (2) a novel single-base pair deletion within codon 277 (1176delT) that results in a premature stop codon; (3) a novel single-base pair deletion within codon 179 (880delG) that produces a substitution of arginine instead of alanine and a premature stop codon 17 amino acids downstream from the last original amino acid, and (4) a duplication (or insertion) of ten base pairs within codon 404 (1556dupATGCCACCAC) that results in a premature stop codon 26 amino acids after the last original amino acid. We also observed in 2 nonrelated patients a deletion of 13 bp (1410_1422delGAGTGCAGGCAGA) previously reported for other populations. Conclusion: We reported four novel mutations and a novel polymorphic variant in the CYP1B1 gene in PCG in the Mexican population; it has important implications in diagnosis and genetic counseling.

Steroid sulfatase deficiency results in X-linked ichthyosis, an inborn error of metabolism in which the principal molecular defect is the complete deletion of the steroid sulfatase gene and flanking markers. Mosaicism for the steroid sulfatase gene has not yet been reported in X-linked ichthyosis. In this study we describe an X-linked ichthyosis patient with complete deletion of the steroid sulfatase gene and his mother with somatic and germinal mosaicism for this molecular defect. The family (X-linked ichthyosis patient, grandmother, mother, and sister) was analyzed through steroid sulfatase enzyme assay, polymerase chain reaction, DNA markers, and fluorescence in situ hybridization of the steroid sulfatase gene. Steroid sulfatase activity was undetectable in the X-linked ichthyosis patient, very low in the mother, and normal in the grandmother and sister. The X-linked ichthyosis patient showed a 2 Mb deletion of the steroid sulfatase gene and flanking regions from 5'DXS1139 to 3'DXF22S1. The mother showed one copy of the steroid sulfatase gene in 98.5% of oral cells and in 80% of leukocytes. The grandmother and sister showed two copies of the steroid sulfatase gene. The origin of the X chromosome with the deletion of the steroid sulfatase gene corresponded to the grandfather of the proband. We report the first case of somatic and germinal mosaicism of the steroid sulfatase gene in an X-linked ichthyosis carrier and propose DNA slippage as the most plausible mechanism in the genesis of this mosaicism.

The β adrenergic receptors (ADRB) are expressed in the ciliary body and trabecular meshwork, structures involved in aqueous humor production and outflow, respectively. ADRB are members of the adrenergic family of G-protein-coupled receptors. Topic β blockers have a good local and systemic tolerance; they reduce the aqueous humor production and eye strain blocking the ADRB of the ciliary body and interfering with adenylate cyclase. However, the ocular hypotensive response is not the same in all patients and could be mediated by the polymorphisms of the ADRB genes.Seventy-two healthy subjects were studied after treatment with topical betaxolol in both eyes. We analyzed ADRB1 and ADRB2 gene polymorphisms by PCR and automated DNA sequencing.There was statistically significant difference between baseline intraocular pressure (IOP) and final IOP of both eyes (baseline IOP 16.2 ± 1.2 - follow-up IOP 13.6 ± 2.0 (mean difference-2.5 ± 1.3, p 0.001). Gly389 had a higher baseline IOP than Arg389 (17.0 ± 1.2 mmHg versus 16.0 ± 1.2 mmHg; p = 0.02), and conversely Arg389 had a greater magnitude of response than Gly389 to betaxolol therapy (-2.9 ± 1.1 mmHg versus -0.7 ± 0.4 mmHg; p 0.001). Gln27 had a higher response than Glu27 (-2.7 ± 1.3 mmHg versus -1.9 ± 1.0; p = 0.02).Arg389 polymorphism of the ADRB1 gene and Gln27 polymorphism of the ADRB2 gene were associated with the hypotensive response to topic betaxolol in healthy Mexican volunteers.

Purpose To report discordant retinoblastoma in monozygotic twins, confirmed by GeneScan. Methods One twin presented unilateral retinoblastoma that was treated with enucleation; the other twin had no retinoblastoma. To confirm monozygosity, DNA from leukocytes was analyzed through GeneScan with highly polymorphic markers; to exclude 13q14 deletion, FISH analysis was performed in leukocytes and oral cells of both twins and their parents and in retinal tissue of the affected twin with the cDNA LSI RB1 probe. Results GeneScan analysis confirmed monozygosity. 13q14 deletion was observed in homozygous state in retinal tissue and in heterozygous state in oral cells and leukocytes of the affected twin. The nonaffected twin and parents showed no deletion of 13q14. Conclusions These data show unexpected differences in monozygotic twins that could be explained by postzygotic events in embryonic development.

X-linked ichthyosis (XLI) is an inherited disorder due to steroid sulfatase deficiency (STS). Most XLI patients (>90%) have complete deletion of the STS gene and flanking sequences. The presence of low copy number repeats (G1.3 and CRI-S232) on either side of the STS gene seems to play a role in the high frequency of these interstitial deletions. In the present study, we analyzed 80 Mexican patients with XLI and complete deletion of the STS gene. STS activity was measured in the leukocytes using 7-[3H]-dehydroepiandrosterone sulfate as a substrate. Amplification of the regions telomeric-DXS89, DXS996, DXS1139, DXS1130, 5′ STS, 3′ STS, DXS1131, DXS1133, DXS237, DXS1132, DXF22S1, DXS278, DXS1134-centromeric was performed through PCR. No STS activity was detected in the XLI patients (0.00 pmoles/mg protein/h). We observed 3 different patterns of deletion. The first two groups included 25 and 32 patients, respectively, in which homologous sequences were involved. These subjects showed the 5′ STS deletion at the sequence DXS1139, corresponding to the probe CRI-S232A2. The group of 32 patients presented the 3′ STS rupture site at the sequence DXF22S1 (probe G1.3) and the remaining 25 patients had the 3′ STS breakpoint at the sequence DXS278 (probe CRI-S232B2). The third group included 23 patients with the breakpoints at several regions on either side of the STS gene. No implication of the homologous sequences were observed in this group. These data indicate that more complex mechanisms, apart from homologous recombination, are occurring in the genesis of the breakpoints of the STS gene of XLI Mexican patients.

Pycnodysostosis (OMIM # 265800) is an inherited lysosomal disorder due to affection of cathepsin K gene, localised to 1q21. Pycnodysostosis can present with both skeletal and extraskeletal features. The index patient presented with cardinal features of short stature, dental and digital anomalies with history of multiple fractures. He, in addition had an unreported finding of white matter hyperintensity suggesting dysmyelination on neuroimaging. Molecular analysis revealed a homozygous insertion of single nucleotide in exon 5 of the CTSK gene that produces the substitution of phenylalanine instead of leucine at position 160 of protein and a premature termination of protein synthesis due to insertion of a stop codon. This mutation (c.480_481insT), (p.L160fsX173) is a novel frameshift mutation. The index case extends the phenotypic spectrum and the list of previously reported mutations in the CTSK gene.

Objective. To describe the case of a pregnant woman and her fetus with Noonan syndrome (NS) whom were diagnosed through ultrasonography 3D and molecular analysis of the PTPN11 gene.Study design. Case report.Results. We detected in a pregnant woman and her child the G

A 70-year-old male presented with very large, thick, tightly adherent, dark-brown scales on the front of his lower extremities. His face, neck, back, abdomen, upper extremities, flexural areas, palms and soles as well as hair and nails were not involved. Family history was negative for similar lesions. Otherwise, the patient had a normal development. Onset of symptoms occurred during childhood with scales on lower extremities with no more additional features. Treatment included emollients exclusively with partial and temporary remission of cutaneous lesions. Recently, the patient had not received topical or systemic medical treatment. Laboratory investigations were within normal limits. The patient had undetectable levels of STS activity when compared with normal control (0.00 pmol mg(-1) protein h(-1)) which confirmed the diagnosis of X-linked ichthyosis (XLI) . PCR analysis showed deletion of the STS gene, markers DXS1139 and DXF22S1and the 5' end of the VCX3A gene. The patient had scales present on lower extremities only with no medical treatment that corresponded to an unusual clinical manifestation of XLI. Clinical manifestations of XLI are due to a great variety of environmental, genetic and individual factors that should be considered in XLI diagnosis.