Differential mutational profiles of familial Mediterranean fever in North Africa

Familial Mediterranean fever (FMF) is a recessive autoinflammatory disease, mainly occurring in the eastern Mediterranean. In these populations, the five FMF founder mutations are differently distributed. In Algeria, the FMF-causing variants remain poorly explored. This retrospective study aims to report the mutational profile of Algerian FMF patients and to compare it with North African FMF patients. One hundred eighty-three unrelated patients clinically suspected of FMF were recruited from various Algerian hospitals (2007–2015) and tested for mutations in exon 10 of MEFV gene. Molecular analysis identified 144 mutant alleles among 87 of 183 patients (47.5%). p.M694I was the most prevalent pathogenic allele, accounting for 63.2% of mutant alleles, followed by p.M694V and p.M680I occurring with a same frequency (14.5%). Others, p.A744S (6.2%) and p.I692del (1.3%), are less frequent. Interestingly, p.M694I was the most recurrent in patients with renal AA-amyloidosis. Our results provide the first genetic data on FMF in Algeria, demonstrating the predominance of p.M694I and the absence of p.V726A, compared to other North African countries (Morocco, Tunisia, and Egypt). In conclusion, North African FMF patients display differential mutational profiles that may result from the difference in ethnic origin and the genetic heterogeneity among these populations.     

Novel APP K724M mutation causes Chinese early-onset familial Alzheimer's disease and increases amyloid-β42 to amyloid-β40 ratio

Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly individuals. Although there are several million cases of AD estimated in China with the most population in the world, no Chinese early-onset familial AD caused by new APP gene mutation has ever been reported. Here, we first described a Chinese family with early-onset AD that was inherited in autosomal dominant manner, and the age of onset was 46.6 ± 7.7 years (n = 5; range, 40–58 years). By using genetic analysis of 3 collected patients' DNA samples, we identified a heterozygous APP gene mutation (g.275363A>T, K724M according to APP770). Finally, when APP695 with K724M mutation was ectopically expressed in HEK293 cell, the ratio of amyloid-β42 to amyloid-β40 was 2.23-fold higher than that of wild-type control. Together, our data suggest that APP K724M gene mutation may contribute to the cause of this Chinese early-onset familial AD.     

Unusual variability of PRRT2 linked phenotypes within a family

BackgroundMutations in the proline-rich transmembrane protein 2 (PRRT2) gene on chromosome 16p11.2 have recently been identified as a cause of paroxysmal kinesigenic dyskinesias (PKD), infantile convulsions and choreoathetosis (ICCA) syndrome or infantile convulsions (IC).AimsHere, we describe a family with four affected members. They all suffer from different diseases: febrile convulsion, epileptic seizures, PKD or headache.MethodsThe whole coding region of PRRT2 gene has been analyzed.ResultsMolecular testing revealed the PRRT2 gene mutation c649.delC in exon 2 for all three sibs as well as for the mother.ConclusionOur presented family case shows the great variability within PRRT2 linked phenotypes even within the same family. Further and more detailed studies will be needed before genetic findings enter into the daily diagnostic and the daily genetic counseling with all its consequences.     

Possible Neoangiogenesis in Achilles Tendon Xanthoma with Familial Hypercholesterolemia: A Novel Approach to Achilles Tendon Xanthoma

Achilles tendon xanthoma (ATX) is one of the typical features of familial hypercholesterolemia (FH). The morphological evaluation of ATX by X-ray radiography is widely recognized; however, the utility of other imaging modalities remains unclear. We herein report two cases of FH in which Doppler ultrasound imaging demonstrated a microvascular flow in ATX that only rarely could be observed in normal Achilles tendons. Neoangiogenesis accompanies chronic inflammation and it may play an important role in the deposition of cholesterol crystals leading to ATX. In addition to the morphological evaluation of ATX, the assessment of neoangiogenesis may therefore be essential for the evaluation of ATX.     

Sponastrime dysplasia: Five new cases and review of nine previously published cases

Sponastrime dysplasia (SD) is a dwarfing autosomal recessive short-limb bone dysplasia. The diagnosis is established by a combination of clinical and radiological findings of which the radiological are the more specific. The current diagnostic criteria are ambiguous as demonstrated by the fact that, in our opinion, three of the five patients reported since the original article do not have this condition. Comparison of our five patients and the 9 published patients has led to development of more specific diagnostic criteria. Previously undescribed complications of this condition are subglottic stenosis and tracheo-broncho-malacia, developmental coxa vara, and avascular necrosis of the capital femoral epiphyses. © 1996 Wiley-Liss, Inc.     

Clinical similarities in siblings with schizophrenia

Three symptom groups, identified by factor analysis of schizophrenic symptoms, together with other clinical variables, were compared among 80 sibships (169 individuals), containing two or more members affected with schizophrenia. The three factors, which were labelled negative symptom, disorganization, and reality distortion, all showed a moderate but significant degree of correlation between siblings. Age at onset was also significantly correlated. Such a familial pattern of clinical heterogeneity suggests underlying common familial aetiologies that influence the clinical form of the disorder. Whether these are genetic or environmental requires further investigation. This finding confers some external validation on the three factor model. It may be feasible to develop familial symptom patterns as the basis for an a priori approach to linkage heterogeneity. © 1996 Wiley-Liss, Inc.     

Unbalanced translocation in a mother and her son in one of two 5;10 translocation families

We present two families with different distal long arm 5;10 translocations. In one family the propositus and his mother inherited the same derived chromosome 10 from the maternal grandfather who has a balanced t(5;10)(q35.3;q26.13). The phenotype of both the affected patients is milder and only partially overlaps with that of previous cases of distal 10q deletion. Other previously reported cases of transmitted imbalance are also remarkable for mild phenotype, occurrence of deletions rather than duplications and a strong bias toward maternal as opposed to paternal transmission. In the second family, the propositus inherited a derived chromosome 10 from his mother who carries a balanced t(5;10)(q35.1;q26.3) translocation; his clinical manifestations are consistent with an emerging phenotype for distal 5q duplications. © 1996 Wiley-Liss, Inc.