Biallelic variants in genes previously associated with dominant inheritance: CACNA1A, RET and SLC20A2.

A subset of families with co-dominant or recessive inheritance has been described in several genes previously associated with dominant inheritance. Those recessive families displayed similar, more severe, or even completely different phenotypes to their dominant counterparts. We report the first patients harboring homozygous disease-related variants in three genes that were previously associated with dominant inheritance: a loss-of-function variant in the CACNA1A gene and two missense variants in the RET and SLC20A2 genes, respectively. All patients presented with a more severe clinical phenotype than the corresponding typical dominant form. We suggest that co-dominant or recessive inheritance for these three genes could explain the phenotypic differences from those documented in their cognate dominant phenotypes. Our results reinforce that geneticists should be aware of the possible different forms of inheritance in genes when WES variant interpretation is performed. We also evidence the need to refine phenotypes and inheritance patterns associated with genes in order to avoid failures during WES analysis and thus, raising the WES diagnostic capacity in the benefit of patients.

Application of QF-PCR for the prenatal assessment of discordant monozygotic twins for fetal sex.

OBJECTIVE: To establish the utility of quantitative fluorescent polymerase chain reaction (QF-PCR) in order to determine the zygosity of multiple pregnancies, as well as to define the origin of the most frequent aneuploidies in amniotic fluid samples. METHODS: We describe the case of a monochorionic (MC) diamniotic (DA) pregnancy with phenotypically discordant twins (nuchal cystic hygroma and non-immune hydrops in twin A and no anomalies in twin B). QF-PCR was performed for rapid prenatal diagnosis in uncultured amniocytes and subsequently in cultured cells. Polymorphic markers for chromosomes X, Y, 13, 18 and 21 were used for determination of zygosity as well as sex chromosome aneuploidy. RESULTS: Twin A showed a Turner Syndrome (TS) mosaicism pattern by QF-PCR in uncultured amniocytes. The monozygotic origin of the pregnancy was determined. Interphase fluorescence in situ hybridization (I-FISH) in this sample showed a mosaicism X0/XY (83/17%). Cytogenetic analysis revealed a 45,X0 karyotype in twin A and a 46,XY karyotype in twin B. CONCLUSIONS: QF-PCR is a reliable tool for the determination of the zygosity independently of the chorionicity and the fetal sex in case of twin pregnancy. Testing both direct and cultured cells can provide useful results for genetic counselling in chromosomal mosaicisms.

[Pneumonia in elder institutionalized patients:derivation and/or prognostic classification criterion]. / Neumoní en el anciano institucionalizado: criterios de derivación y/o clasificación pronóstica.

OBJECTIVE: To know the clinical features of nursing home residents with pneumonia comparing with patients with Community-acquired pneumonia and identify the main prognostic index of mortality. MATERIAL AND METHODS: Longitudinal prospective study including all the elderly patients hospitalized in Cantoblanco Hospital of Madrid during the year 2001 for pneumonia and classified according to the Fine prognosis index and the SEPAR criteria. RESULTS: Of the 78 patients with pneumonia, 27 came from Residence, with an average of age of 86.85(+/- 6.43) years old, opposite to 83.11 (+/- 5.87) years in patients with Community acquired pneumonia ( p<0.05). Of all of them, 33,3% belonged to class IV and 66.7% to class V of Fine. Of all the variables studied, only the age (p= 0.03) and the hypoxemia (p= 0.03) were statistical significant. CONCLUSIONS: Nursing home residents with pneumonia are older and have more prevalence of morbi-mortality than those with Community acquired pneumonia. In our study, the age and the hypoxemia were the two independent prognosis factors associate to more mortality.

Neumonía en el anciano institucionalizado: criterios de derivación y/o clasificación pronóstica / Pneumonia in elder institutionalized patients: derivation and/or prognostic classification criterion

Objetivo: Conocer el perfil clínico de los pacientes con neumonía procedentes de Residencia comparándolo con los de neumonía adquirida en la comunidad (NAC) no institucionalizados e identificar los principales índices pronósticos de mortalidad. Material y métodos: Estudio prospectivo longitudinal de todos los ancianos ingresados en el Hospital de Cantoblanco de Madrid durante el año 2001 diagnosticados de neumonía y clasificados según el índice pronóstico de Fine y los criterios de la SEPAR. Resultados: De los 78 pacientes con neumonía, 27 procedían de Residencia, con una edad media de 86,85 (ñ 6,43) años, frente a 83,11 (ñ 5,87) años en los procedentes de domicilio (p<0,05). De ellos, el 33,3 por ciento pertenecían a la clase IV y el 66,7 por ciento a la clase V de Fine. De todas las variables estudiadas, sólo la edad (p= 0,03) y la hipoxemia (p= 0,01) fueron estadísticamente significativas. Conclusiones: Los pacientes con neumonía procedentes de Residencia tienen mayor edad y mayor prevalencia de morbi-mortalidad que los procedentes de su domicilio. En nuestro estudio, la edad y la hipoxemia son los dos factores pronósticos independientes asociados a mayor mortalidad (AU)

Karyotype and prognosis in adult Spanish acute lymphoblastic leukemia.

The aim of the study was to define the frequency and prognostic significance of acquired chromosomal abnormalities in our adult population and to ascertain whether karyotype represents a significant prognostic factor in adult patients with acute lymphoblastic leukemia (ALL) independently of the new intensive chemotherapy programs and initial clinical characteristics.

[Genetics of congenital cardiopathies]. / Genética de las cardiopatías congénitas.

Congenital heart malformations are the most common of all birth defects, affecting 0.5-1% of all live births. Some of these malformations are due to genetic anomalies. Patterns of autosomal dominant, autosomal recessive and X-linked inheritance have been described. Mitochondrial inheritance and chromosomal anomalies can also be responsible for congenital heart malformations. Several genes for congenital heart defects have been identified. We review current knowledge on the genetic etiology of congenital heart disease.

Transient congenital hypoparathyroidism and 22q11 deletion.

CATCH-22 syndrome represents a spectrum of abnormalities associated with microdeletions of chromosome 22q11. We report a patient with transient congenital hypoparathyroidism, with severe neonatal hypocalcemia and spontaneous resolution in infancy, tetralogy of Fallot and thymic hypoplasia. Genetic confirmation of chromosome 22q11 deletion was made. Newborns with congenital hypoparathyroidism need genetic analysis and examination for anomalies associated with CATCH-22 syndrome.

Genética de las cardiopatías congénitas / Congenital heart malformations

Las cardiopatías son las malformaciones congénitas más frecuentes, afectan al 0,5-1 por ciento de los recién nacidos vivos. Una parte son de origen genético. Se han visto patrones de herencia autosómica dominante, autosómica recesiva, herencia ligada al cromosoma X y herencia mitocondrial. Pueden ser también causadas por anomalías cromosómicas. Se han identificado varios genes responsables de cardiopatías congénitas. En este artículo revisamos el estado actual de conocimiento de las cardiopatías congénitas de origen genético (AU)