Unique association of hypochondroplasia with craniosynostosis and cleft palate in a Mexican family.

Hypochondroplasia (HCH) is a skeletal dysplasia caused by an abnormal function of the fibroblast growth factor receptor 3. Although believed to be relatively common, its prevalence and phenotype are not well established owing to its clinical, radiological, and genetic heterogeneity. Here we report on a molecularly proven HCH family with an affected father and two children. The siblings (male and female) with HCH also had craniosynostosis and cleft palate, respectively. The present report supports the conclusion that the full clinical spectrum of HCH is not completely delineated. It also suggests that secondary, as yet unknown, modifying factors can influence the final phenotype.

Partial and complete trisomy 14 mosaicism: clinical follow-up, cytogenetic and molecular analysis.

BACKGROUND: Trisomy 14 mosaicism is a rare chromosomal abnormality. It is associated with multiple congenital anomalies. We report a 15 year-old female with an unusual karyotype with three cell lines: 47,XX,+mar/47,XX,+14/46,XX. At six months old she had short stature, cleft palate, hyperpigmented linear spots in arms and legs and developmental delay. At present, she has mild facial dysmorphism and moderate mental retardation. METHODS: Cytogenetic analysis was performed in peripheral blood lymphocytes and in the light and dark skin following standard methods. DNAarray - Oligo 180 k was carried out using Agilent Technologies and FISH analysis was accomplished using DNA BACs probes to confirm the result obtained by DNAarray. Methylation-Specific PCR (MS-PCR) of the MEG3 promoter and microsatellite analysis were performed. RESULTS: Microarray analysis confirmed partial trisomy 14 mosaicism; the marker chromosome was found to be from chromosome 14, the result was confirmed with FISH. Methylation (14q32.3) and microsatellite (14q11-14q32.33) analysis were carried out and UPD was discarded. The global result was: mos 47,XX,+del(14)(q11.2)[45]/47,XX,+14[10]/46,XX[45]. CONCLUSIONS: This is a unique case because of the coexistence of two abnormal cell lines, including one with +14 and another with +del(14)(q11.2). To our knowledge, only three patients have been reported with trisomy 14 and another abnormal cell line. The array analysis identified the marker chromosome and characterized the breakpoint. The del(14)(q11.2) does not seem to be related to any particular phenotypic characteristic of the patient; the clinical features of our patient observed until now, can be attributed to trisomy 14 mosaicism. Nevertheless, we cannot discard the manifestation of new symptoms related to her karyotype in the future.

Cytogenomic and phenotypic analysis in low-level monosomy 7 mosaicism with non-supernumerary ring chromosome 7.

We present the literature review of ring chromosome 7 and clinical, cytogenetic and fine molecular mapping of the first postnatal report of a male child with a non-supernumerary ring chromosome 7, r(7). The patient had dysmorphic features, developmental delay, dermatologic lesions with variable pigmentation, hypogenitalism, lumbar dextroscoliosis, cerebellar and ophthalmological abnormalities, and melanocytic congenital nevi. Cytogenetic analysis of peripheral blood and the nevus sample showed the presence of three different cell lines r(7), monosomy 7, and duplicated r(7) (idic r(7)), while findings on fibroblasts from both light and dark skin showed only mosaicism with r(7) and monosomy 7 cell lines in various proportions. FISH assay of the ring chromosome showed subtelomeric loss in both chromosome arms in all tissues studied. Analysis by genome-wide single-nucleotide polymorphism array showed a 0.8 Mb deletion in 7p22.3 (involving eight genes) and a 7.5 Mb deletion in 7q36 (involving 29 genes including some involved in genital and central nervous system development). The combination of results from our karyotypic and array analyses enabled us to establish an accurate genotype-phenotype relationship.

Variabilidad clínica citogenética en doce familias mexicanas con anemia de Fanconi y su relación con el grupo de complementación al que pertenecen / Clinical and cytogenetic variability on twelve Fanconi anemia families and its relationship with complementation group assignment

Objetivo. Describir las caractetísticas clínica y citogenéticas en pacientes mexicanos con anemia de Fanconi y determinar si la variabilidad fenotípica se relaciona con el grupo de complementación. Material y métodos. Se hizo el diagnóstico citogenético por exposición de linfocitos de sangre periférica a mitomicina C y a diepoxibutano. Se clasificaron, la gravedad de la anemia y las manifestaciones clínica utilizando las puntuaciones de alter y Auerbach respectivamente. Se establecieron líneas linfoblastoides de ocho individuos y se determinó el grupo de complementación mediante fusión celular en cuatro casos índices. Resultados. se estudiaron 12 familias con 25 afectados. Los pacientes mostraron frecuencias elevadas de aberraciones cromosómicas espontáneas e inducidas; no existió relación con la gravedad clínica o estado anémico. El cuadro clínico se clasificó como grave en 12 pacientes y como leve en 13. La anemia no se presentó en tres enfermos, fue leve en 13, moderadas en siete y grave en uno. La mortalidad fue del 32 por ciento (8/25). No hubo relación entre puntuación clínica, grado de anemia y defunción. Once pacientes se asignaron al grupo de complementación A con cuadro clínico y anemia leves; sus resultados citogenéticos mostraron variabilidad. Un paciente fue asignado al grupo C, obtuvo una puntuación clínica grave, anemia dependiente de transfusión y alta sensibilidad a mutágenos. Trece sujetos no fueron clasificados, en tres pacientes se obtuvo una línea linfoblastoide resistente a mitomicina C, que sugirió mosaicismo somático. Conclusiones. El grupo de complementación no explica la variabilidad; existen otros factores como el mosaicismo somático que modifica el fenotipo celular