Mesoaxial synostotic syndactyly with phalangeal reduction (MSSD) is an extremely rare autosomal recessive limb abnormality characterized by the fusion of third and fourth fingers. To date, only ...homozygous missense and frameshift mutations have been reported in BHLHA9 associated to MSSD. In this study, we report a patient who presented with clinical and radiological features of MSSD. A customized skeletal dysplasia NGS panel revealed the presence of two novel compounds heterozygous variants in BHLHA9: NM_001164405.1: c.226A>T269G>C; p.(Lys76*)(Arg90Pro). Thus, this is the first case of MSSD in a nonconsanguineous family.
Ectodermal dysplasias (ED) are a group of genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives. An attenuated phenotype is considered a non-syndromic ...trait when the patient is affected by only one impaired ectodermal structure, such as in non-syndromic tooth agenesis (NSTA) disorder. Hypohidrotic ectodermal dysplasia (HED) is the most highly represented ED. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common subtype, with an incidence of 1/50,000-100,000 males, and is associated with the EDA gene (Xq12-q13.1); the dominant and recessive subtypes involve the EDAR (2q13) and EDARADD (1q42.3) genes, respectively. The WNT10A gene (2q35) is associated more frequently with NSTA. Our goal was to determine the mutational spectrum in a cohort of 72 Spanish patients affected by one or more ectodermal derivative impairments referred to as HED (63/72) or NSTA (9 /72) to establish the prevalence of the allelic variants of the four most frequently associated genes. Sanger sequencing of the EDA, EDAR, EDARADD and WNT10A genes and multiplex ligation-dependent probe amplification (MLPA) were performed.
A total of 61 children and 11 adults, comprising 50 males and 22 females, were included. The average ages were 5.4 and 40.2 years for children and adults, respectively. A molecular basis was identified in 51/72 patients, including 47/63 HED patients, for whom EDA was the most frequently involved gene, and 4/9 NSTA patients, most of whom had variants of WNT10A. Among all the patients, 37/51 had variants of EDA, 8/51 had variants of the WNT10A gene, 4/51 had variants of EDAR and 5/51 had variants of EDARADD. In 42/51 of cases, the variants were inherited according to an X-linked pattern (27/42), with the remaining showing an autosomal dominant (10/42) or autosomal recessive (5/42) pattern. Among the NSTA patients, 3/9 carried pathogenic variants of WNT10A and 1/9 carried EDA variants. A total of 60 variants were detected in 51 patients, 46 of which were different, and out of these 46 variants, 12 were novel.
This is the only molecular study conducted to date in the Spanish population affected by ED. The EDA, EDAR, EDARADD and WNT10A genes constitute the molecular basis in 70.8% of patients with a 74.6% yield in HED and 44.4% in NSTA. Twelve novel variants were identified. The WNT10A gene has been confirmed as the second molecular candidate that has been identified and accounts for one-half of non-EDA patients and one-third of NSTA patients. Further studies using next generation sequencing (NGS) will help to identify other contributory genes in the remaining uncharacterized Spanish patients.
Cell suffer structural and metabolic changes in stress situations,which allow them to maintain an adequate homeostasis and avoid death . This bibliographic review had the objective of describing the ...main morph-physiological changes which occur in cardiac failure and cardiac-pulmonary-cerebral resuscitation. The method was documentary reviewing (database Regional SciELO, PubMed, Cochrane and Infomed), developed during the first semester of 2018. Twenty eight references were selected. It was concluded that there are cellular changes during circulatory stop, the procedures of resuscitation and re-perfusion. In cardiac failure, cellular changes are expressed in all the organelles. And may cause death due to necroses. During re-perfusion new structural changes occur, for calcium entrance, sodium disturbances, production of free radicals and swelling. Morph.physiological changes depend on previous metabolic condition, time of cardiac failure and the successful establishment of resuscitation measures.
Las células realizan transformaciones estructurales y metabólicas ante situaciones de estrés, lo que les permite mantener una adecuada homeostasis y evitar la muerte. La presente revisión ...bibliográfica tuvo como objetivo describir los principales cambios morfofisiológicos celulares que acontecen en la parada cardiaca y reanimación cardiopulmocerebral. El método incluyó una revisión documental (bases de datos SciELO Regional, PubMed, Cochrane e Infomed), realizada durante el primer semestre del 2018. Fueron seleccionadas 28 referencias. Se concluye que existen cambios celulares durante el cese circulatorio, las maniobras de resucitación y en la reperfusión. En la parada cardiaca, los cambios celulares se expresan en todos los organelos y puede llevar a muerte por necrosis. Durante la reperfusión se producen nuevos cambios estructurales, por entrada de calcio, alteraciones en sodio, producción de radicales libres e inflamación. Los cambios morfofisiológicos dependerán del estado metabólico previo, el tiempo de parada cardiaca y la instauración eficaz de medidas de resucitación.
Phelan-McDermid syndrome (PMS, OMIM# 606232) results from either different rearrangements at the distal region of the long arm of chromosome 22 (22q13.3) or pathogenic sequence variants in the
gene.
...codes for a structural protein that plays a central role in the formation of the postsynaptic terminals and the maintenance of synaptic structures. Clinically, patients with PMS often present with global developmental delay, absent or severely delayed speech, neonatal hypotonia, minor dysmorphic features, and autism spectrum disorders (ASD), among other findings. Here, we describe a cohort of 210 patients with genetically confirmed PMS. We observed multiple variant types, including a significant number of small deletions (<0.5 Mb, 64/189) and
sequence variants (21 cases). We also detected multiple types of rearrangements among microdeletion cases, including a significant number with post-zygotic mosaicism (9.0%, 17/189), ring chromosome 22 (10.6%, 20/189), unbalanced translocations (
or inherited, 6.4%), and additional rearrangements at 22q13 (6.3%, 12/189) as well as other copy number variations in other chromosomes, unrelated to 22q deletions (14.8%, 28/189). We compared the clinical and genetic characteristics among patients with different sizes of deletions and with
variants
Our findings suggest that
plays an important role in this syndrome but is probably not uniquely responsible for all the spectrum features in PMS. We emphasize that only an adequate combination of different molecular and cytogenetic approaches allows an accurate genetic diagnosis in PMS patients. Thus, a diagnostic algorithm is proposed.
Drug‐induced lupus erythematosus (DILE) is a less severe variant of systemic lupus erythematosus (SLE) that generally resolves within weeks or months after the withdrawal of the implicated drug. DILE ...is unusual during childhood, with the most frequent age of presentation being at 50–70 years of age. Among different drugs, most commonly procainamide and hydralazine have been implicated as a cause of DILE. However carbamazepine (CBZ) is considered a low‐risk drug and very few cases have been reported in children. We describe the case of CBZ‐induced SLE in a 9‐year‐old girl following 3 years of CBZ therapy. This case report shows that drug‐induced SLE is an important side‐effect to be considered, even after long‐term treatment with CBZ, and also during childhood.
Postaxial polydactyly (PAP) is a frequent limb malformation consisting in the duplication of the fifth digit of the hand or foot. Morphologically, this condition is divided into type A and B, with ...PAP‐B corresponding to a more rudimentary extra‐digit. Recently, biallelic truncating variants in the transcription factor GLI1 were reported to be associated with a recessive disorder, which in addition to PAP‐A, may include syndromic features. Moreover, two heterozygous subjects carrying only one inactive copy of GLI1 were also identified with PAP. Herein, we aimed to determine the level of involvement of GLI1 in isolated PAP, a condition previously established to be autosomal dominantly inherited with incomplete penetrance. We analyzed the coding region of GLI1 in 95 independent probands with nonsyndromic PAP and found 11.57% of these subjects with single heterozygous pathogenic variants in this gene. The detected variants lead to premature termination codons or result in amino acid changes in the DNA‐binding domain of GLI1 that diminish its transactivation activity. Family segregation analysis of these variants was consistent with dominant inheritance with incomplete penetrance. We conclude that heterozygous changes in GLI1 underlie a significant proportion of sporadic or familial cases of isolated PAP‐A/B.
![[Recensão a] Rubén Castro R...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0870-4147/small "[Recensão a] Rubén Castro Redondo, Entre colmos, rebolas e dobres varas de medir: conflitos por medidas na Galicia moderna (séculos XVI-XIX)")
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