ResearchPad - clinical-reports https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Expansion of the phenotype of lateral meningocele syndrome]]> https://www.researchpad.co/article/elastic_article_8284 Lateral meningocele syndrome (LMS) is due to specific pathogenic variants in the last exon of NOTCH3 gene. Besides the lateral meningoceles, this condition presents with dysmorphic features, short stature, congenital heart defects, and feeding difficulties. Here, we report a girl with neurosensorial hearing loss, severe gastroesophageal reflux disease, congenital heart defects, multiple renal cysts, kyphosis and left‐convex scoliosis, dysmorphic features, and mild developmental delay. Exome sequencing detected the previously unreported de novo loss‐of‐function variant in exon 33 of NOTCH3 p.(Lys2137fs). Following the identification of the gene defect, MRI of the brain and spine revealed temporal encephaloceles, inner ears anomalies, multiple spinal lateral meningoceles, and intra‐ and extra‐dural arachnoid spinal cysts. This case illustrates the power of reverse phenotyping to establish clinical diagnosis and expands the spectrum of clinical manifestations related to LMS to include inner ear abnormalities and multi‐cystic kidney disease.

]]>
<![CDATA[Paternal mosaicism for a novel <i>PBX1</i> mutation associated with recurrent perinatal death: Phenotypic expansion of the <i>PBX1</i>‐related syndrome]]> https://www.researchpad.co/article/elastic_article_7108 Autosomal dominant (de novo) mutations in PBX1 are known to cause congenital abnormalities of the kidney and urinary tract (CAKUT), with or without extra‐renal abnormalities. Using trio exome sequencing, we identified a PBX1 p.(Arg107Trp) mutation in a deceased one‐day‐old neonate presenting with CAKUT, asplenia, and severe bilateral diaphragmatic thinning and eventration. Further investigation by droplet digital PCR revealed that the mutation had occurred post‐zygotically in the father, with different variant allele frequencies of the mosaic PBX1 mutation in blood (10%) and sperm (20%). Interestingly, the father had subclinical hydronephrosis in childhood. With an expected recurrence risk of one in five, chorionic villus sampling and prenatal diagnosis for the PBX1 mutation identified recurrence in a subsequent pregnancy. The family opted to continue the pregnancy and the second affected sibling was stillborn at 35 weeks, presenting with similar severe bilateral diaphragmatic eventration, microsplenia, and complete sex reversal (46, XY female). This study highlights the importance of follow‐up studies for presumed de novo and low‐level mosaic variants and broadens the phenotypic spectrum of developmental abnormalities caused by PBX1 mutations.

]]>
<![CDATA[Novel compound heterozygous stop‐gain mutations of <i>LRBA</i> in a Vietnamese patient with Common Variable Immune Deficiency]]> https://www.researchpad.co/article/elastic_article_6649 We describe the clinical, immunological, and genetic analyses of a Vietnamese patient presenting with typical and atypical symptoms of common variable immune deficiency. Whole exome sequencing revealed novel compound stop‐gain mutations of LRBA. Our findings also expand the already broad range of known CVID clinical phenotypes and contribute to the understanding of phenotype–genotype correlation in LRBA deficiency.

]]>
<![CDATA[Clinical and genetic data of 22 new patients with <i>SMAD3</i> pathogenic variants and review of the literature]]> https://www.researchpad.co/article/elastic_article_6643 Pathogenic SMAD3 variants are responsible for a cardiovascular phenotype, mainly thoracic aortic aneurysms and dissections, with variable expressivity and incomplete penetrance. To investigate the clinical variability observed within SMAD3 patients, we reviewed the data of 22 new patients from our Centre and of 133 patients reported in the literature. We first aimed to delineate an estimated frequency of the main clinical signs associated with SMAD3 pathogenic variants and, then, to look for genotype‐phenotype correlations. We showed herein the absence of correlation between the SMAD3 variant type and the occurrence of an aortic phenotype in patients. This report brings additional data for the genotype‐phenotype correlations of SMAD3 variants and the need to explore in more detail the effects of genetic modifiers that could influence the phenotype.

]]>
<![CDATA[Profound intellectual disability caused by homozygous TRAPPC9 pathogenic variant in a man from Malta]]> https://www.researchpad.co/article/elastic_article_6639 A man previously diagnosed with autism spectrum disorder secondary to intellectual disability, absent speech and repetitive behaviors was found to have homozygous pathogenic variants in TRAPPC9. In the context of the currently reported 48 known cases of TRAPPC9 pathogenic variants, his phenotype is consistent with previously reported phenotypes. Interestingly, it is found that, although the known pathogenic variants do not cluster in respect to location within the gene, the known cases all appears to be from a localized geographic area.

]]>
<![CDATA[A preliminary computational outputs versus experimental results: Application of sTRAP, a biophysical tool for the analysis of SNPs of transcription factor‐binding sites]]> https://www.researchpad.co/article/elastic_article_6626 We tested sTRAP to do some analysis on DNA variations in the cognate binding sites of specific transcription factors, for which there were the results of the experimental approaches, in the literature. At the same time, we compared the results of both of the procedures with the data of another bioinformatics model RAVEN, as an alternative one.

]]>
<![CDATA[Novel compound heterozygous pathogenic variants in <i>ASCC1</i> in a Chinese patient with spinal muscular atrophy with congenital bone fractures 2 : Evidence supporting a "Definitive" gene‐disease relationship]]> https://www.researchpad.co/article/elastic_article_6622 Spinal muscular atrophy with congenital bone fractures 2.

]]>
<![CDATA[Rapid detection by <i>hydrops panel</i> of Noonan syndrome with <i>PTPN11</i> mutation (p.Thr73Ile) and persistent thrombocytopenia]]> https://www.researchpad.co/article/elastic_article_6615 Nonimmunological hydrops fetalis (NIHF) is still a challenging diagnosis. The success of identifying a cause depends on the thoroughness of efforts to establish a diagnosis. We report a premature with NIHF. The hydrops panel revealed Noonan syndrome (NS) with a mutation in PTPN11 c.218C>T (p.Thr73Ile). The variant of c.218C>T (p.Thr73Ile) has not yet been described in literature relating to NIHF. Only a few case reports of this variant are known.

]]>
<![CDATA[Acute renal failure in SARS patients: more than rhabdomyolysis]]> https://www.researchpad.co/article/Nbbfed95f-6d43-44a8-b16b-eae50d3a58c3 ]]> <![CDATA[Severe acute respiratory syndrome in haemodialysis patients: a report of two cases]]> https://www.researchpad.co/article/N158221e7-56aa-48d1-80f3-e83a15978391 ]]> <![CDATA[Clinical efficacy of irinotecan plus raltitrexed chemotherapy in refractory esophageal squamous cell cancer]]> https://www.researchpad.co/article/Ned7d0368-9077-4603-b9da-9bdbf8b41742

Our retrospective study assessed the efficacy and safety of irinotecan plus raltitrexed in esophageal squamous cell cancer (ESCC) patients who were previously treated with multiple systemic therapies. Between January 2016 and December 2018, records of 38 ESCC patients who underwent irinotecan plus raltitrexed chemotherapy after at least one line of chemotherapy were reviewed. Efficacy assessment was performed every two cycles according to the RECIST version 1.1. A total of 95 cycles of chemotherapy were administered, and the median course was 3 (range 2–6). There was no treatment-related death. Nine patients had partial response, 21 had stable disease and eight had progressive disease. The overall objective response rate was 23.68% (9/38) and the disease control rate was78.94% (30/38). After a median follow-up of 18.5 months, the median progression-free survival and overall survival were 105 and 221 days, respectively. There were five patients (13.15%) with grade 3/4 leukopenia, three patients (7.89%) with grade 3/4 neutropenia and one patient (2.63%) with grade 3/4 diarrhea. The combination of irinotecan plus raltitrexed was effective for pretreated ESCC patients. Further studies are needed to determine the optimal dose of the two drugs.

]]>
<![CDATA[A Syrian patient with Steel syndrome due to compound heterozygous COL27A1 mutations with colobomata of the eye]]> https://www.researchpad.co/article/Na7068733-8a24-4fe8-a99d-b515021d59c7

Abstract

The joint occurrence of short stature, congenital dislocation of the hip, carpal coalition, dislocation of the radial head, cavus deformity, scoliosis, and vertebral anomalies was first described in 1993 by Steel et al. (OMIM #615155) in 23 children from Puerto Rico. The condition is caused by a deficient matrix protein, collagen type XXVII alpha 1 chain, due to bi‐allelic loss of function mutations in the gene COL27A1. Outside of Puerto Rico, only four families have been described, in three of which the patients also had hearing loss. However, structural eye defects have not yet been reported in conjunction with this rare autosomal recessive syndrome. Here, we describe a 9‐year‐old girl born to nonconsanguineous Syrian parents with the characteristic features of Steel syndrome, including short stature, massive malalignment of large joints, kyphoscoliosis, hearing loss, and typical facial dysmorphism. However, she was also born with bilateral colobomata of the irides and choroido‐retinae with unilateral affection of the macula. Whole exome sequencing identified two pathogenic compound heterozygous variants in COL27A1: c.93del, p.(Phe32Leufs*71) and c.3075del, p.(Lys1026Argfs*33). There was no discernible alternative cause for the colobomata. Our findings might indicate an association of this exceptionally rare disorder caused by COL27A1 mutations with developmental defects of the eye from the anophthalmia/microphthalmia/coloboma spectrum.

]]>
<![CDATA[Possible mitochondrial dysfunction in a patient with deafness, dystonia, and cerebral hypomyelination (DDCH) due to BCAP31 Mutation]]> https://www.researchpad.co/article/Ne0d84645-73e1-4368-a9b6-b5dfcde0024a

Abstract

Background

Deafness, dystonia, and cerebral hypomyelination (DDCH) is an X‐linked disorder due to hemizygous mutations of BCAP31.

Methods

We report an 8‐year‐old boy with DDCH who possibly accompanied mitochondrial dysfunction. Clinical evaluation, respiratory chain enzyme assay, and whole exome sequencing analysis were performed.

Results

Mitochondrial dysfunction was suspected by respiratory chain enzyme assay on his cultured skin fibroblasts which showed significantly decreased complex I enzyme activity. Whole exome sequencing analysis revealed a recurrent BCAP31 mutation (c.97C>T:p.Gln33*) which confirmed the diagnosis of DDCH for the patient.

Conclusion

We speculate that mitochondrial dysfunction may be a feature in patients with DDCH.

]]>
<![CDATA[MeCP2_e2 partially compensates for lack of MeCP2_e1: A male case of Rett syndrome]]> https://www.researchpad.co/article/N063677fe-31a0-4e55-8cd1-c2a62a069201

Abstract

Background

Rett syndrome (RTT) is a neurodevelopmental disorder that predominantly affects girls. Its causative gene is the X‐linked MECP2 encoding the methyl‐CpG‐binding protein 2 (MeCP2). The gene comprises four exons and generates two isoforms, namely MECP2_e1 and MECP2_e2. However, it remains unclear whether both MeCP2 isoforms have similar function in the brain.

Methods

We report a case of a boy with typical RTT. Male cases with MECP2 variants have been considered inviable, but somatic mosaicism of the variants can cause RTT in males. Whole‐exome sequencing was performed to search for the genetic background.

Results

A novel nonsense and mosaic variant was identified in exon 1 of MECP2, and the variant allele fraction (VAF) was 28%. Our patient had the same level of VAF as that in reported male cases with mosaic variants in MECP2 exon 3 or 4, but manifested RTT symptoms that were milder in severity compared to those in these patients.

Conclusion

This is probably because the variants in MECP2 exon 3 or 4 disrupt both isoforms of MeCP2, whereas the variant in exon 1, as presented in this study, disrupts only MeCP2_e1 but not MeCP2_e2. Therefore, our findings indicate that MeCP2_e2 may partially compensate for a deficiency in MeCP2_e1.

]]>
<![CDATA[Split‐Sided Chest Study of Skin Rejuvenation Comparing Low‐Energy, 1,927‐nm Thulium Fractional Laser Treatment Prior to Photodynamic Therapy Versus Photodynamic Therapy Alone]]> https://www.researchpad.co/article/Nf36cfa1d-095a-4714-b91c-be9b269bd46b

Background and Objectives

Treatment of photoaging and intrinsic aging of the chest, with the associated concerns of skin roughness, uneven pigmentation, laxity, atrophy, and telangiectasias, can be problematic because of the potential for worsened esthetic outcomes with existing treatments. This study assessed the efficacy and safety of using nonablative fractional laser therapy (FLT) pretreatment with photodynamic therapy (PDT) versus PDT alone for chest rejuvenation.

Study Design/Materials and Methods

In a randomized, evaluator‐blinded, split‐sided study, adult female patients with photodamage to the chest received three treatment courses over an 8‐week period with follow‐up visits at Weeks 12 and 20. FLT was applied to one side of the chest, randomly assigned at baseline, followed by aminolevulinic acid‐based PDT, delivered using a thermal, short incubation, broad area technique, to both sides of the chest. In‐person and photographic assessments were conducted using five‐point scales to evaluate outcomes including rhytides, pigmentation, skin texture, and telangiectasias.

Results

Eleven adults completed the study, of whom 11 had improved scores for rhytides and 10 had improved scores for skin texture at Week 20. There was no significant difference in any efficacy outcome between FLT and PDT and standard PDT alone. The severity of adverse events was rated significantly greater with the combined FLT–PDT treatment vs PDT alone.

Conclusions

Significant improvements were observed vs baseline for both sides of the chest treated with FLT–PDT or standard PDT following three treatment sessions. No significant difference in efficacy was observed between treatment approaches, although adverse events were more severe on the FLT‐pretreated side. This study was not registered as it qualified as a nonsignificant risk study. Lasers Surg. Med. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

]]>
<![CDATA[Increased Tattoo Fading in a Single Laser Tattoo Removal Session Enabled by a Rapid Acoustic Pulse Device: A Prospective Clinical Trial]]> https://www.researchpad.co/article/N13d5f654-9079-4d72-8308-4f75afb8d251

Background and Objectives

The ability to provide improved tattoo fading using multiple laser passes in a single office laser tattoo removal session is limited. In part, this is due to the loss of laser effectiveness caused by epidermal and dermal vacuole “whitening” generated during the initial laser pass at the tattoo site. The Rapid Acoustic Pulse (RAP) device generates acoustic shock wave pulses that clear epidermal and dermal vacuoles to enable multiple laser passes in a single office laser tattoo removal session. The objectives of this study were to determine if the RAP device, when used as an accessory to the 1064 nm Nd:YAG Q‐switched (QS) laser can enable delivery of multiple laser passes in a single office laser tattoo removal session, and therefore result in increased tattoo fading compared to the clinical standard single‐pass QS laser tattoo removal session.

Study Design/Materials and Methods

The RAP device was evaluated in a single‐center (SkinCare Physicians), prospective, IRB approved study. A total of 32 black ink tattoos, from 21 participants, were divided into three zones and treated with either multiple QS laser passes, each followed by 1 minute of RAP device application (Laser + RAP) in zone one and single‐pass QS laser treatment (Laser‐Only) in zone two, separated by an untreated control zone. The treatment sites were assessed for the number of laser passes and adverse events immediately, 6 weeks, and 12 weeks following the treatment session. Photographs of the treatment sites were assessed for percent fading at 12 weeks post‐treatment by three blinded reviewers.

Results

When the RAP device was applied as an accessory to the QS laser in a multi‐pass laser tattoo removal treatment, an average of 4.2 laser passes were delivered in a single session, with no unexpected or serious RAP device‐related adverse events. At the 12‐week follow‐up, tattoos treated with Laser + RAP showed a statistically significant increase in average fading (44.2%) compared with tattoos treated with Laser‐Only (24.8%) (P < 0.01). Additionally, a significantly higher overall proportion of tattoos treated with Laser + RAP (37.5%) had a response of >50% fading compared with tattoos treated with QS Laser‐Only (9.4%) (P < 0.01) as well as a response of >75% fading from Laser + RAP treatment (21.9%) compared with Laser‐Only treatment (3.1%) (P < 0.05).

Conclusions

The RAP device, applied as an accessory to the 1064 nm Nd:YAG QS laser, safely enables multiple QS laser treatments in a single office laser tattoo removal session by clearing the whitening caused by the previous QS laser pass. Enabling multiple QS laser passes results in a statistically significant increase in tattoo fading in a single office laser tattoo removal session compared to the clinical standard single‐pass QS laser tattoo removal session. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

]]>
<![CDATA[Survival outcomes of adjuvant chemotherapy with modified weekly nab-paclitaxel and carboplatin for completely resected nonsmall cell lung cancer: FAST-nab]]> https://www.researchpad.co/article/N0d8e2ec8-9a97-4ca4-a145-6125abb29302

The relatively low toxicity profile of nab-paclitaxel plus carboplatin and its feasibility as an adjuvant administration was reported previously. This study aimed to evaluate the survival efficacy for completely resected patients with stage IB, II, and IIIA nonsmall cell lung cancer (NSCLC). Twenty-nine eligible patients with NSCLC who received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-paclitaxel (nab-P) (100 mg/m2) on days 1 and 8 followed by carboplatin area (area under the curve = 6) on day 1 were prospectively enrolled and assessed for survival outcomes against patients with the same stages who received other postoperative adjuvant chemotherapy regimens during the same period. There were no significant differences in clinicopathological features, including age, gender, smoking status, performance status, surgical procedures, tumor histology, and pathological stage between the two groups. The cumulative overall survival (OS) rates at 5 years of the experimental and control groups in pathological stage IB–IIIA were 85.4% and 63.9%, respectively (P = 0.598), while recurrence-free survival (RFS) rates in these groups at 5 years were 65.2% and 34.8%, respectively (P = 0.344). Moreover, the cumulative OS rates of the experimental and control groups in pathological stage II–IIIA were 83.6% and 63.6%, respectively (P = 0.970), while RFS rates in these groups at 5 years were 61.1% and 37.3%, respectively (P = 0.460). This new regimen was considered an attractive alternative postoperative adjuvant chemotherapy option with relatively low toxicity and moderate survival outcomes for completely resected NSCLC.

]]>
<![CDATA[Prehospital Ground Transport Rapid Sequence Intubation for Trauma and Traumatic Brain Injury Outcomes]]> https://www.researchpad.co/article/5c8bf7d4d5eed0c484b1e815 ]]> <![CDATA[Tumor calcification as a prognostic factor in cetuximab plus chemotherapy-treated patients with metastatic colorectal cancer]]> https://www.researchpad.co/article/5c8010b9d5eed0c484a97edf

Supplemental Digital Content is available in the text.

]]>
<![CDATA[Dyssegmental dysplasia, Silverman‐Handmaker type: A challenging antenatal diagnosis in a dizygotic twin pregnancy]]> https://www.researchpad.co/article/5b5b78fc463d7e1e0134c315

Abstract

Background

Dyssegmental dysplasia Silverman‐Handmaker (DDSH; MIM 224410) type is an extremely rare skeletal dysplasia caused by functional null mutations in the perlecan gene. Less than forty cases are reported in the literature, of which only four were prenatally detected.

Methods

We report on a dizygotic twin pregnancy from consanguineous parents for which one of the twins presented prenatally with severe micromelia, limb bowing and scoliosis, and postnatally with clinical and radiological features compatible with a diagnosis of dyssegmental dysplasia. Molecular studies were undertaken to confirm the clinical diagnosis of DDSH.

Results

Molecular analysis results revealed a novel homozygous variant in the HSPG2 gene (MIM 142461), NM_005529.6(HSPG2):c.4029 + 1G>A, consistent with a diagnosis of DDSH.

Conclusion

To the best of our knowledge, the current report is only the seventh molecularly confirmed case of DDSH.

]]>