Facial Asymmetry and Congenital Anomalies in Newborn Cousins

Yeni doğan bebeklerde fasiyal asimetri her zaman fasiyal paralizi olduğu anlamına gelmez. Konjenital fasiyal asimetri, doğumsal travmatik fasiyal paraliziye bağlı olabileceği gibi, “konjenital asimetrik ağlayan yüz” olarak adlandırılan depresor anguli oris kasının aplazisi (DAOA) nedeniyle de olabilmektedir. İzole kas aplazilerine, iskelet, kardiyovaskuler, ürogenital, solunum ve santral sinir sistemi anomalileri eşlik edebilir. Burada sunulan DAOA’li hastanın kuzeninde iki elde 8 parmak aplazisi, kalça çıkığı, bilateral ayak parmaklarında parsiyel kutanöz sindaktili ve ASD mevcuttur. DAOA, kulak burun boğaz ve pediatri doktorları tarafından bilinmesi gereken, etiyolojisi netleşmemiş, karşılaşıldığı vakit ek tarama tetkiki gerektiren, konjenital bir anomalidir.Facial asymmetry in new-born babies is not always due to facial paralysis. Congenital facial asymmetry, might as well as be due to depressor anguli oris muscle aplasia (DAOA), so called “congenital asymmetric crying facies”. Additional congenital anomalies like skeletal, cardiovascular, urogenital, respiratory or central nerve system anomalies can also accompany this disorder. Here, we present a case with DAOA whose cousin had aplasia of 8 fingers in two hands, hip dislocation, partial cutaneous syndactyly in bilateral feet fingers, and ASD. DAOA is a rare congenital anomaly with unknown etiology; therefore, screening tests should be done when encountered by otolaryngologists and pediatricians

Nuchal Translucency Measurement Did Not Significantly Predict Trisomy Cases in Tertiary Referral Center

OBJECTIVE: We sought to determine the value of well defined screening method in predicting trisomy cases in our institution. STUDY DESIGN: Totally 300 amniocentesis cases were screened from prospectively collected database. Subjects were referred to amniocentesis according to the sequential results of first and second trimester screening tests. Each case had nuchal translucency measurement between 11th to 14th weeks of gestation. All values of NT measurement were analyzed to predict trisomy cases. RESUlTS:There were 7 trisomy cases , non of the screening methods significantly predicted trisomy cases (p>0.05) rather than the simply age (Area under curve 0.724, p=0.043). Mean NT did not differ between groups with normal and abnormal chromosomes(p>0.05). CONClUSION: This data led us to conclude that in our country there is still need for more accurate and standardized method to predict abnormal cases with higher sensitivity and specificiy to decrease invasive procedures

Mutations in ANKLE2, a ZIKA Virus Target, Disrupt an Asymmetric Cell Division Pathway in Drosophila Neuroblasts to Cause Microcephaly

The apical Par complex, which contains atypical protein kinase C (aPKC), Bazooka (Par-3), and Par-6, is required for establishing polarity during asymmetric division of neuroblasts in Drosophila, and its activity depends on L(2)gl. We show that loss of Ankle2, a protein associated with microcephaly in humans and known to interact with Zika protein NS4A, reduces brain volume in flies and impacts the function of the Par complex. Reducing Ankle2 levels disrupts endoplasmic reticulum (ER) and nuclear envelope morphology, releasing the kinase Ballchen-VRK1 into the cytosol. These defects are associated with reduced phosphorylation of aPKC, disruption of Par-complex localization, and spindle alignment defects. Importantly, removal of one copy of ballchen or l(2)gl suppresses Ankle2 mutant phenotypes and restores viability and brain size. Human mutational studies implicate the above-mentioned genes in microcephaly and motor neuron disease. We suggest that NS4A, ANKLE2, VRK1, and LLGL1 define a pathway impinging on asymmetric determinants of neural stem cell division. © 2019 Elsevier Inc. The Zika virus protein NS4A interacts with ANKLE2, a protein linked to hereditary microcephaly. Mutations in ANKLE2 also cause microcephaly-like phenotypes in flies. Link et al. now connect these phenotypes with disruption of an asymmetric cell division pathway in fly neuroblasts via an interaction between ANKLE2 and the kinase Ballchen-VRK1

The phenotypic and molecular genetic spectrum of Alström syndrome in 44 Turkish kindreds and a literature review of Alström syndrome in Turkey.

Alström syndrome (ALMS) is an autosomal recessive disease characterized by multiple organ involvement, including neurosensory vision and hearing loss, childhood obesity, diabetes mellitus, cardiomyopathy, hypogonadism, and pulmonary, hepatic, renal failure and systemic fibrosis. Alström Syndrome is caused by mutations in ALMS1, and ALMS1 protein is thought to have a role in microtubule organization, intraflagellar transport, endosome recycling and cell cycle regulation. Here, we report extensive phenotypic and genetic analysis of a large cohort of Turkish patients with ALMS. We evaluated 61 Turkish patients, including 11 previously reported, for both clinical spectrum and mutations in ALMS1. To reveal the molecular diagnosis of the patients, different approaches were used in combination, a cohort of patients were screened by the gene array to detect the common mutations in ALMS1 gene, then in patients having any of the common ALMS1 mutations were subjected to direct DNA sequencing or next-generation sequencing for the screening of mutations in all coding regions of the gene. In total, 20 distinct disease-causing nucleotide changes in ALMS1 have been identified, eight of which are novel, thereby increasing the reported ALMS1 mutations by 6% (8/120). Five disease-causing variants were identified in more than one kindred, but most of the alleles were unique to each single patient and identified only once (16/20). So far, 16 mutations identified were specific to the Turkish population, and four have also been reported in other ethnicities. In addition, 49 variants of uncertain pathogenicity were noted, and four of these were very rare and probably or likely deleterious according to in silico mutation prediction analyses. ALMS has a relatively high incidence in Turkey and the present study shows that the ALMS1 mutations are largely heterogeneous; thus, these data from a particular population may provide a unique source for the identification of additional mutations underlying Alström Syndrome and contribute to genotype-phenotype correlation studies. J Hum Genet 2015 Jan; 60(1):1-9

Exome Sequencing of a Primary Ovarian Insufficiency Cohort Reveals Common Molecular Etiologies for a Spectrum of Disease.

Context: Primary ovarian insufficiency (POI) encompasses a spectrum of premature menopause, including both primary and secondary amenorrhea. For 75% to 90% of individuals with hyper-gonadotropic hypogonadism presenting as POI, the molecular etiology is unknown. Common etiologies include chromosomal abnormalities, environmental factors, and congenital disorders affecting ovarian development and function, as well as syndromic and nonsyndromic single gene disorders suggesting POI represents a complex trait