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Eye (Lond) 2021 Apr 12. Epub 2021 Apr 12.

Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China.

Objectives: To delineate the disease-causing mutations of the Stargardt disease-related genes in Chinese patients diagnosed with Stargardt disease or retinitis pigmentosa (RP) by whole exome sequencing analysis.

Methods: A total of 123 sporadic RP or Stargardt disease patients and 2 Stargardt disease families were recruited. All sporadic patients and the probands of the families were subjected to whole exome sequencing analysis. Read More

Genome Med 2021 Apr 12;13(1):55. Epub 2021 Apr 12.

Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.

Background: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored protein involved in diverse processes including mitochondrial dynamics, mitochondrial DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), and heterozygous missense variants or duplications (antimorph) in ATAD3A lead to neurological syndromes in humans.

Methods: To expand the mutational spectrum of ATAD3A variants and to provide functional interpretation of missense alleles in trans to deletion alleles, we performed exome sequencing for identification of single nucleotide variants (SNVs) and copy number variants (CNVs) in ATAD3A in individuals with neurological and mitochondrial phenotypes. Read More

Electrophoresis 2021 Apr 9. Epub 2021 Apr 9.

Department of Forensic Medicine, Kurume University School of Medicine, Kurume, 830-0011, Japan.

FUT2 encodes galactoside 2-α-L-fucosyltransferase 2 which determines the secretor status of ABO(H) blood group antigens. Secretors have at least one functional FUT2 allele (Se), while non-secretors or weak-secretors are homozygous for nonfunctional (non- or weak-secretor) FUT2 alleles (se or Se ). The Se having the 385A>T missense SNP (rs1047781) is the prevalent nonfunctional allele in East and Southeast Asians. Read More

Nat Commun 2021 04 8;12(1):2107. Epub 2021 Apr 8.

Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Vacuolar H-ATPases (V-ATPases) transport protons across cellular membranes to acidify various organelles. ATP6V0A1 encodes the a1-subunit of the V0 domain of V-ATPases, which is strongly expressed in neurons. However, its role in brain development is unknown. Read More

Klin Padiatr 2021 Apr 8. Epub 2021 Apr 8.

Institute of Biochemistry and Biotechnology, Pir Mehar Ali Shah Arid Agriculture University, Rawalpindi, Pakistan.

Background: Tay-Sachs disease (TSD) is a rare autosomalrecessive genetic disorder characterized by progressive destruction of nerve cells in the brain and spinal cord. It is caused by genetic variations in the HEXA gene leading to a deficiency of β hexosaminidase A (HEXA) isoenzyme activity. This study aimed to identify causative gene variants in 3 unrelated consanguineous families presented with TSD from Pakistan and Morocco. Read More

J Mol Neurosci 2021 Apr 6. Epub 2021 Apr 6.

School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a multi-system disorder caused by several homozygous or compound heterozygous mutations, mostly in the nuclear gene of TYMP. Our current knowledge on the underlying pathology of the disease is derived through the study of about 200 cases of different ethnicities. Clinical presentations include severe cachexia, weakness, ptosis, diplopia, abdominal cramps or digestive tract disorders, hearing impairment, and paresthesia. Read More

J Neurogenet 2021 Apr 6:1-6. Epub 2021 Apr 6.

Department of Human Pathology of the Adult and Developmental Age "Gaetano Barresi", Unit of Child Neurology and Psychiatry, University of Messina, Messina, Italy.

The (Solute Carrier Family 25, Member 22) gene encodes for a mitochondrial glutamate/H symporter and is involved in the mitochondrial transport of metabolites across the mitochondrial membrane. We hereby report a 12-year-old girl presenting with early-onset epileptic encephalopathy, hypotonia, and global developmental delay. Whole exome sequencing identified a novel homozygous missense mutation in gene (c. Read More

Adv Biomed Res 2020 28;9:70. Epub 2020 Nov 28.

Department of Pediatrics, Kalinga Institute of Medical Sciences, KIIT Deemed to be University, Bhubaneswar, Odisha, India.

Dystroglycanopathy is a type of congenital muscular dystrophy caused by mutations causing defective glycosylation of a dystrophin-associated glycoprotein, dystroglycan and as such is a very rare disease entity. We are reporting a 1-year-old girl child with dystroglycanopathy who presented with motor predominant developmental delay. She had motor development quotient of 52, mental development quotient of 75, facial dysmorphism, mixed hypotonia with a global decrease in muscle power, and areflexia. Read More

Hum Genet 2021 Apr 3. Epub 2021 Apr 3.

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Teebi hypertelorism syndrome (THS; OMIM 145420) is a rare craniofacial disorder characterized by hypertelorism, prominent forehead, short nose with broad or depressed nasal root. Some cases of THS have been attributed to SPECC1L variants. Homozygous variants in CDH11 truncating the transmembrane and intracellular domains have been implicated in Elsahy-Waters syndrome (EWS; OMIM 211380) with hypertelorism. Read More

Mol Genet Genomic Med 2021 Apr 3:e1657. Epub 2021 Apr 3.

Department of Auricular Reconstruction, Chinese Academy of Medical Sciences and Peking Union Medical College Plastic Surgery Hospital, Beijing, China.

Background: Microtia is a congenital malformation of the external ear and may occur as an isolated deformity or as part of a syndrome. Our previous study found a high correlation between microtia and thoracic deformities, thus, we propose that external ear and thorax development may be regulated by certain genes in common.

Methods: We performed exome sequencing on 10 families of sporadic microtia with thoracic abnormalities. Read More

Genes (Basel) 2021 Mar 5;12(3). Epub 2021 Mar 5.

Department of Biotechnology and Genetic Engineering, Kohat University of Science & Technology (KUST), Kohat 26000, Khyber Pakhtunkhwa, Pakistan.

Background: Ichthyoses are a large group of hereditary cornification disorders, which are both clinically and etiologically heterogeneous and affect mostly all the skin surface of the patients. Ichthyosis has its origin in an ancient Greek word "ichthys" meaning fish, this is because the ichthyosis patients have dry, thickened, and scaly skin. There is an excess accumulation of epidermal cells resulting in the appearance of continuous and widespread scales on the body. Read More

Genes (Basel) 2021 Mar 24;12(4). Epub 2021 Mar 24.

Institute of Veterinary Medicine, University of Goettingen, 37077 Göttingen, Germany.

Congenital deafness is prevalent among modern dog breeds, including Australian Stumpy Tail Cattle Dogs (ASCD). However, in ASCD, no causative gene has been identified so far. Therefore, we performed a genome-wide association study (GWAS) and whole genome sequencing (WGS) of affected and normal individuals. Read More

Int J Mol Sci 2021 Mar 27;22(7). Epub 2021 Mar 27.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98122 Messina, Italy.

Background: Retinitis pigmentosa punctata albescens (RPA) is a particular form of retinitis pigmentosa characterized by childhood onset night blindness and areas of peripheral retinal atrophy. We investigated the genetic cause of RPA in a family consisting of two affected Egyptian brothers with healthy consanguineous parents.

Methods: Mutational analysis of four RPA causative genes was realized by Sanger sequencing on both probands, and detected variants were subsequently genotyped in their parents. Read More

Sci Rep 2021 Apr 1;11(1):7320. Epub 2021 Apr 1.

Departamento de Bioquímica, UAM-CSIC, Facultad de Medicina UAM, 28029, Madrid, Spain.

DJ-1/PARK7 mutations are linked with familial forms of early-onset Parkinson's disease (PD). We have studied the degradation of untagged DJ-1 wild type (WT) and missense mutants in mouse embryonic fibroblasts obtained from DJ-1-null mice, an approach closer to the situation in patients carrying homozygous mutations. The results showed that the mutants L10P, M26I, A107P, P158Δ, L166P, E163K, and L172Q are unstable proteins, while A39S, E64D, R98Q, A104T, D149A, A171S, K175E, and A179T are as stable as DJ-1 WT. Read More

Gynecol Endocrinol 2021 Mar 31:1-4. Epub 2021 Mar 31.

Division of Pediatric Endocrinology, Dr. Behçet Uz Children's Education and Research Hospital, Izmir, Turkey.

Introduction: Persistent müllerian duct syndrome (PMDS) is a rare form of 46, XY disorder of sex development characterized by the persistence of the müllerian structures (uterus, fallopian tubes, the upper part of the vagina) in phenotypically and genotypically normal males. This disease occurs as a result of impairment in the synthesis, release or effect of anti-Müllerian hormone (AMH) during the embryonic period. Approximately 85-88% of PMDS cases have been reported to have or mutation. Read More

Acta Neurol Belg 2021 Mar 30. Epub 2021 Mar 30.

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Progressive myoclonus epilepsies (PMEs) are a group of disorders embracing myoclonus, seizures, and neurological dysfunctions. Because of the genetic and clinical heterogeneity, a large proportion of PMEs cases have remained molecularly undiagnosed. The present study aimed to determine the underlying genetic factors that contribute to the PME phenotype in an Iranian female patient. Read More

J Clin Lab Anal 2021 Mar 26:e23768. Epub 2021 Mar 26.

Department of Biology, Faculty of Science, Yazd University, Yazd, Iran.

Background: Familial adenomatous polyposis (FAP) as a colon cancer predisposition syndrome is an autosomal-dominant inherited condition and is diagnosed by the progress of hundreds or thousands of adenomatous colonic polyps in the colon. This study aims at the nature and effect of Adenomatous Polyposis Coli (APC) gene mutations in FAP tumorigenesis.

Methods: The genetic screening of 59 FAP Iranian patients in 10 families was performed by polymerase chain reactions and the direct sequencing of the entire coding exons of the APC gene. Read More

J Hum Genet 2021 Mar 25. Epub 2021 Mar 25.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

In recent years, the tropomyosin-receptor kinase fused gene (TFG) has been linked to diverse hereditary neurodegenerative disorders, including a very rare complex hereditary spastic paraplegia, named spastic paraplegia type 57 (SPG57). Until now, four pathogenic homozygous variants of the TFG gene have been reported associated with SPG57. Two consanguineous Iranian families (1 and 2), the first one with two affected members and the second one with one, all with an early-onset progressive muscle weakness, spasticity, and several neurological symptoms were examined via the whole-exome sequencing. Read More

Eur J Med Genet 2021 Mar 23;64(5):104200. Epub 2021 Mar 23.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Animal Models for Human Diseases, Changsha, China. Electronic address:

SETD2 encodes an important protein for epigenetic modification of histones which plays an essential role in early development. Variants in SETD2 have been reported in neurodevelopmental disorders including autism spectrum disorder (ASD). However, most de novo SETD2 variants were reported in different large-cohort sequencing studies, mutation pattern and comprehensive genotype-phenotype correlations for SETD2 are still lacking. Read More

Eur J Paediatr Neurol 2021 Mar 5;32:40-45. Epub 2021 Mar 5.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, Ramat Gan, Israel.

Background: and Purpose: Postnatal progressive microcephaly, with seizures and brain atrophy (OMIM # 613668) is a rare disorder caused by a homozygous founder missense mutation c.1112T>C (p.L371P) in the MED17 gene on chromosome 11 that was identified in 2010 in Caucasus Jewish families. Read More

BMC Neurol 2021 Mar 9;21(1):105. Epub 2021 Mar 9.

Human Genetics Unit, Department of Anatomy, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka.

Background: Collagen VI-related dystrophies are a subtype of congenital muscular dystrophy caused by pathogenic variants in COL6A1, COL6A2 or COL6A3 genes affecting skeletal muscles and connective tissue. The clinical phenotype ranges from the milder Bethlem myopathy to the severe Ullrich congenital muscular dystrophy (UCMD). Herein, we report the first consanguineous Sri Lankan family with two children affected with UCMD due to a novel variant in the COL6A1 gene. Read More

Autism Res 2021 Mar 22. Epub 2021 Mar 22.

Laboratory of Neurogenetics and Molecular Medicine - IPER, Institut de Recerca Sant Joan de Déu, Barcelona, Spain.

Autism spectrum disorder (ASD) is a neurodevelopmental disability with high heritability yet the genetic etiology remains elusive. Therefore, it is necessary to elucidate new genotype-phenotype relationships for ASD to improve both the etiological knowledge and diagnosis. In this work, a copy-number variant and whole-exome sequencing analysis were performed in an ASD patient with a complex neurobehavioral phenotype with epilepsy and attention deficit hyperactivity disorder. Read More

Thromb Haemost 2021 Mar 19. Epub 2021 Mar 19.

Oslo University Hospital, Department of Medical Genetics, Oslo, Norway.

Clinical parameters have been extensively studied in factor (F) VII deficiency, but the knowledge of molecular mechanisms of this disease is scarce. We report on three probands with intracranial bleeds at early age, one of which had concomitant high titer of FVII inhibitor. The aim of the present study was to identify the causative mutations and to elucidate the underlying molecular mechanisms. Read More

Pituitary 2021 Mar 20. Epub 2021 Mar 20.

Department of Endocrinology, IndiaSeth G.S. Medical College & KEM Hospital, Parel, Mumbai, Maharashtra, 400012, India.

Context: POU1F1 mutations are prevalent in Indian CPHD cohorts. Genotype-phenotype correlation is not well-studied.

Aim: To describe phenotypic and genotypic spectrum of POU1F1 mutations in our CPHD cohort and present systematic review as well as genotype-phenotype analysis of all mutation-positive cases reported in world literature. Read More

Neuromuscul Disord 2021 Feb 16. Epub 2021 Feb 16.

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.

We evaluated the clinical histories, motor and pulmonary functions, cardiac phenotypes and GAA genotypes of an Indian cohort of twenty patients with late onset Pompe disease (LOPD) in this multi-centre study. A mean age at onset of symptoms and diagnosis of 9.9 ± 9. Read More

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 Jan 28:4564. Epub 2021 Jan 28.

Division of Diagnostic Radiology, Department of Radiology, Faculty of Medicine, Chiang Mai University.

Objective: Our objective was to investigate the molecular etiology of osteogenesis imperfecta type VIII and dental anomalies in 4 siblings of a Karen tribe family.

Materials And Methods: Four patients and their unaffected parents were studied by clinical and radiographic examination. In situ hybridization of P3h1 during early murine tooth development, whole-exome sequencing, and Sanger direct sequencing were performed. Read More

Orphanet J Rare Dis 2021 Mar 18;16(1):136. Epub 2021 Mar 18.

Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 10, 91054, Erlangen, Germany.

Background: An identical homozygous missense variant in EIF3F, identified through a large-scale genome-wide sequencing approach, was reported as causative in nine individuals with a neurodevelopmental disorder, characterized by variable intellectual disability, epilepsy, behavioral problems and sensorineural hearing-loss. To refine the phenotypic and molecular spectrum of EIF3F-related neurodevelopmental disorder, we examined independent patients.

Results: 21 patients were homozygous and one compound heterozygous for c. Read More

Hum Mol Genet 2021 Mar 17. Epub 2021 Mar 17.

Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

Adaptor protein 2 (AP2), a heterotetrameric complex comprising AP2α, AP2β2, AP2μ2 and AP2σ2 subunits, is ubiquitously expressed and involved in endocytosis and trafficking of membrane proteins, such as the calcium-sensing receptor (CaSR), a G-protein coupled receptor that signals via Gα11. Mutations of CaSR, Gα11 and AP2σ2, encoded by AP2S1, cause familial hypocalciuric hypercalcaemia types 1-3 (FHH1-3), respectively. FHH3 patients have heterozygous AP2S1 missense Arg15 mutations (p. Read More

Medicine (Baltimore) 2021 Mar;100(10):e24161

Neonatal Screening Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou.

Abstract: Propionic acidemia is associated with pathogenic variants in PCCA or PCCB gene. We investigated the potential pathogenic variants in PCCA or PCCB genes in Fujian Han population.Two probands and their families of Han ethnicity containing two generations were subject to newborn screening using tandem mass spectrometry, followed by diagnosis using urine gas chromatography mass spectrometry. Read More

Mol Genet Genomic Med 2021 Mar 16:e1630. Epub 2021 Mar 16.

MAGI's Lab, Genetic Testing Laboratory, Rovereto, Italy.

Background: The rapid spread of genome-wide next-generation sequencing in the molecular diagnosis of rare genetic disorders has produced increasing evidence of multilocus genomic variations in cases with a previously well-characterized molecular diagnosis. Here, we describe two patients with a rare combination of skeletal abnormalities and retinal dystrophy caused by variants in the SLC26A2 and ABCA4 genes, respectively, in a family with parental consanguinity.

Methods: Next-generation sequencing and Sanger sequencing were performed to obtain a molecular diagnosis for the retinal and skeletal phenotypes, respectively. Read More