Phenotype of Patients With Charcot-Marie-Tooth With the p.His123Arg Mutation in GDAP1 in Northern Finland

Background and ObjectivesMutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene cause autosomal dominant or autosomal recessive forms of Charcot-Marie-Tooth disease (CMT). Our aim was to study the clinical phenotype of patients with CMT caused by heterozygous p.His123Arg in GDAP1.MethodsTwenty-three Finnish patients were recruited from a population-based cohort and through family investigation. Each patient was examined clinically and electrophysiologically. The Neuropathy Symptom Score and the Neuropathy Disability Score (NDS) were used in clinical evaluation.ResultsThe median age at onset of symptoms was 17 years among patients with p.His123Arg in GDAP1. Motor symptoms were markedly more common than sensory symptoms at onset. All patients had distal weakness in lower extremities, and 17 (74%) patients had proximal weakness. Muscle atrophy and pes cavus were also common. Nineteen (82%) patients had sensory symptoms such as numbness or pain. The disease progressed with age, and the NDS increased 8.5 points per decade. Electrodiagnostic testing revealed length-dependent, sensory and motor axonal polyneuropathy. EDx findings were asymmetrical in 14 patients. Genealogic study of the families suggested a founder effect.DiscussionWe found that CMT in patients with p.His123Arg in GDAP1 is relatively mild and slow in progression.

Pulmonary Alveolar Microlithiasis - Report of Two New Cases and Review of the Literature

INTRODUCTION: Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disease characterized by the intra-alveolar accumulation of spherical calcified microliths, of a phospho-calcium nature, in the absence of any problem of phosphocalcium metabolism. The majority of patients are asymptomatic. The disease is often diagnosed on routine radiological examination.CASE REPORTS: We report two cases of PAM; A 17-year-old girl with three generations of consanguinity, who consulted for bronchial syndrome. Auscultation revealed very fine diffuse ronchi. The X-ray showed a bilateral alveolar syndrome, especially on the right, a bilateral bronchointerstitial syndrome, and diffuse bilateral calcifications. The thoracic CT scan showed calcified micro and macronodules with thickening of the septa, middle section involvement with fibrosing remodeling, fibrosis, and tractional bronchiectasis of the bases, pleural and pericardial calcifications. Respiratory function tests showed a restrictive syndrome with a vital capacity of 70% and normal GDS. This radiological and scanographic picture made us think of PAM. We then decided to carry out a family investigation with chest radiographs. All family members had normal radiographs, except for a sister who was three years old, with no particular history, no functional respiratory signs, and no particular complaints. Her chest radiograph showed the famous sandstorm appearance of microcalcifications, with pulmonary distension at the apexes and retractions at the bases. Spirometry and blood gases were normal. Chest CT found microcalcifications, with bilaterally distributed and diffuse ground-glass aspects, with a slight right-hand predominance.CONCLUSION: MLA is known to be radio-clinically dissociative. The diagnosis can be made by radiology alone in typical cases; sometimes, Transbronchial or surgical lung biopsies are needed. The prognosis is compromised in the long term. The only effective treatment nowadays is lung transplantation.

Applied Research of Distinguishing Similar Y-STR Haplotypes by Y Chromosome Complete Sequencing

Background: To explore a technical method to distinguish similar Y-STR haplotypes and its value in deducing the differentiation the males in paternal line, we used a complete genome sequence of Y chromosome using streptavidin–biotin magnetic particle-based capture methodology (Y chromosome liquid phase probe capture next generation sequencing technique (NGS)) to detect male individuals with similar Y-STR haplotypes. Based on our independently developed mathematical model and the new topological structure of Y chromosome mutation sites as well as haplogroups and pedigree trees updated by the International Society of Genealogy (ISOGG) every year, we distinguished the coancestry of male individuals with similar Y-STR haplotypes and Results: Identifying differences between the judgment results of Y full sequencing and the pedigree survey results allowed for the estimation whether the individuals have close relation within 3~5 generations or not. Y chromosome liquid phase probe capture NGS technique could capture the 16M region and effectively analyze tens of thousands of Y-SNP loci. Among them, the coancestry obtained by analysis of 8 sample cases was consistent with the actual total case time obtained by family investigation. Conclusions: Detecting the Y-STR haplotype similarity between male individuals and conducting the previously reported mathematical model analysis by using Y chromosome liquid phase probe capture NGS technology can uncover the coancestry of the different male individuals. These results provide the foundation for further investigation of the similar Y-STR haplotype males in the Y-STR database.

Mothers' and fathers' quantitative and qualitative parenting in relation to children's emotional adjustment: A between- and within-family investigation

This longitudinal study of Australian families (n = 1884, from age 6-12) examined how fathers' and mothers' quantitative involvement (time spent on childcare) and qualitative involvement (specific parenting behaviors) relate to children's emotional adjustment development. We used dynamic structural equation modeling to disentangle stable between-family differences from within-family fluctuations in qualitative parenting and emotional adjustment, allowing us to investigate the direction of effects between parents and children. Because fathers have been theorized to contribute uniquely to emotional adjustment development, we examined differences between mothers and fathers, and the interplay between parent- and child sex. We further examined whether between-family differences in quantitative involvement, operationalized as joint (total) and relative (one parent does more) involvement, predict qualitative parenting behaviors and emotional adjustment, and moderate the within-family interplay between them. Results revealed between-family correlations of qualitative involvement with emotional adjustment. Evidence for significant average within-family effects was limited to a parenting effect of maternal warmth, and several child effects, which indicated that emotional adjustment evokes changes in parenting. Parenting effects varied substantially across families however, especially for fathers. Between-family differences in quantitative involvement explained some of these differences. When joint quantitative involvement was higher, both parents engaged in more desirable qualitative parenting. When mothers were relatively more involved than fathers, fathers displayed less desirable qualitative parenting, and children were less well-adjusted. There was some limited evidence that within-family predictive effects were moderated by quantitative involvement, particularly relative involvement. These findings suggest that all family members benefit from a more equal childcare distribution.

Genome-Wide HMG Family Investigation and Its Role in Glycoalkaloid Accumulation in Wild Tuber-Bearing Solanum commersonii

Steroidal glycoalkaloids (SGAs) are a class of nitrogen-containing glycosides occurring in several plant families and biosynthesized through a specific pathway. HMG-CoA reductase is the first enzyme of this pathway, and its transcription can be regulated by biotic and abiotic stressors and even in a tissue-specific manner. This study aimed to characterize the HMG genes family in a tuber-bearing potato species, Solanum commersonii, using transcriptional and functional approaches. Our results provided evidence that four ScHMGs with different tissue-specificities represent the HMG gene family in S. commersonii and that they originated from ScHMG1 through segmental duplications. Phylogenetic analysis suggests that ScHMG1 is the direct ortholog of AtHMG1, which is associated with SGAs accumulation in plants. Its overexpression in S. commersonii revealed that this gene plays a key role in the accumulation of glycoalkaloids regulating the production of dehydrocommersonine.

Hereditary angioedema: the challenges of cross-border family investigation and treatment

Hereditary angioedema (HAE) is a rare genetic disorder characterised by recurrent swellings involving subcutaneous and submucosal tissue that can be potentially life threatening in cases involving the upper airway. In this case report, we present a Syrian refugee family with HAE who have lived in Denmark since 2014. The index patient is an 8-year-old girl diagnosed with HAE after being hospitalised in Denmark with an angioedema attack. Her younger sister and father were diagnosed later, following investigation of the family. Exploring the family history, deaths due to suffocation were described in previous generations and other family members based in Sweden, Germany, Turkey, Saudi Arabia, USA and Syria could also potentially be affected. This highlights the need for a cross-border effort to diagnose and treat this inherited disorder.