journal
MENU ▼
Read by QxMD icon Read
search

American Journal of Medical Genetics. Part A

journal
https://www.readbyqxmd.com/read/28905509/de-novo-setd5-loss-of-function-variant-as-a-cause-for-intellectual-disability-in-a-10-year-old-boy-with-an-aberrant-blind-ending-bronchus
#1
Claire Green, Joshua Willoughby, Meena Balasubramanian
Although rare, 3p microdeletion cases have been well described in the clinical literature. The clinical phenotype includes; intellectual disability (ID), growth retardation, facial dysmorphism, and cardiac malformations. Advances in chromosome microarray (CMA) testing narrowed the 3p25 critical region to a 124 kb region, and recent Whole Exome Sequencing (WES) studies have suggested that the SETD5 gene contributes significantly to the 3p25 phenotype. Loss-of-Function (LoF) variants in SETD5 are now considered a likely cause of ID...
September 14, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28898547/hlx-is-a-candidate-gene-for-a-pattern-of-anomalies-associated-with-congenital-diaphragmatic-hernia-short-bowel-and-asplenia
#2
Sandra A Farrell, Sandi Sodhi, Christian R Marshall, Andrea Guerin, Anne Slavotinek, Tara Paton, Karen Chong, Wilma L Sirkin, Stephen W Scherer, Félix-Antoine Bérubé-Simard, Nicolas Pilon
Isolated congenital diaphragmatic hernia is often a sporadic event with a low recurrence risk. However, underlying genetic etiologies, such as chromosome anomalies or single gene disorders, are identified in a small number of individuals. We describe two fetuses with a unique pattern of multiple congenital anomalies, including diaphragmatic hernia, short bowel and asplenia, born to first-cousin parents. Whole exome sequencing showed that both were homozygous for a missense variant, c.950A>C, predicting p...
September 12, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28898540/compound-heterozygous-trpv4-mutations-in-two-siblings-with-a-complex-phenotype-including-severe-intellectual-disability-and-neuropathy
#3
My Linh Thibodeau, Colin H Peters, Katelin N Townsend, Yaoqing Shen, Glenda Hendson, Shelin Adam, Kathryn Selby, Patrick M Macleod, Cynthia Gershome, Peter Ruben, Steven J M Jones, Jan M Friedman, William T Gibson, Gabriella A Horvath
TRPV4 encodes a polymodal calcium-permeable plasma membrane channel. Dominant pathogenic mutations in TRPV4 lead to a wide spectrum of abnormal phenotypes. This is the first report of biallelic TRPV4 mutations and we describe two compound heterozygous siblings presenting with a complex phenotype including severe neuromuscular involvement. In light of previously well described dominant inheritance for TRPV4-related neuromuscular disease, our study suggests a role for compound heterozygosity and loss-of-function as a potential novel disease mechanism for this group of disorders...
September 12, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28889642/treating-pediatric-neuromuscular-disorders-the-future-is-now
#4
REVIEW
James J Dowling, Hernan D Gonorazky, Ronald D Cohn, Craig Campbell
Pediatric neuromuscular diseases encompass all disorders with onset in childhood and where the primary area of pathology is in the peripheral nervous system. These conditions are largely genetic in etiology, and only those with a genetic underpinning will be presented in this review. This includes disorders of the anterior horn cell (e.g., spinal muscular atrophy), peripheral nerve (e.g., Charcot-Marie-Tooth disease), the neuromuscular junction (e.g., congenital myasthenic syndrome), and the muscle (myopathies and muscular dystrophies)...
September 10, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28889454/intrafamilial-variability-of-the-triphalangeal-thumb-phenotype-in-a-dutch-population-evidence-for-phenotypic-progression-over-generations
#5
Martijn Baas, Jacob W P Potuijt, Steven E R Hovius, A Jeannette M Hoogeboom, Robert-Jan H Galjaard, Christianne A van Nieuwenhoven
Triphalangeal thumbs (TPTs) are regularly caused by mutations in the ZRS in LMBR1. Phenotypic variability can be present in TPT-families. However, recent observations suggest an increased occurrence of severe phenotypes in the Dutch TPT-population. Therefore, the aim of this study is to investigate the progression of the clinical severity of TPT-phenotype through generations. Index patients from a Dutch TPT-population were identified. A 105C>G mutation in the ZRS has previously been confirmed in this population...
September 10, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884975/pharmacological-interventions-to-improve-cognition-and-adaptive-functioning-in-down-syndrome-strides-to-date
#6
REVIEW
Sarah J Hart, Jeannie Visootsak, Paul Tamburri, Patrick Phuong, Nicole Baumer, Maria-Clemencia Hernandez, Brian G Skotko, Cesar Ochoa-Lubinoff, Xavier Liogier D'Ardhuy, Priya S Kishnani, Gail A Spiridigliozzi
Although an increasing number of clinical trials have been developed for cognition in Down syndrome, there has been limited success to date in identifying effective interventions. This review describes the progression from pre-clinical studies with mouse models to human clinical trials research using pharmacological interventions to improve cognition and adaptive functioning in Down syndrome. We also provide considerations for investigators when conducting human clinical trials and describe strategies for the pharmaceutical industry to advance the field in drug discovery for Down syndrome...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884971/testing-the-face-shape-hypothesis-in-twins-discordant-for-nonsyndromic-orofacial-clefting
#7
Jasmien Roosenboom, Karlijne Indencleef, Greet Hens, Hilde Peeters, Kaare Christensen, Mary L Marazita, Peter Claes, Elizabeth J Leslie, Seth M Weinberg
Nonsyndromic orofacial clefts (OFCs) are complex traits characterized by multifactorial inheritance and wide phenotypic variability. Numerous studies have shown subtle differences in the faces of unaffected relatives from cleft families compared to controls, the implication being that such outward differences are an incomplete expression reflecting an underlying genetic predisposition. Twins discordant for OFCs provide a unique opportunity to further test this idea, as the unaffected co-twin shares on average 50% (for dizygotic twins) and 100% (for monozygotic twins) of the genetic risk factors as the affected twin...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884960/genotypic-phenotypic-features-and-enzyme-replacement-therapy-outcome-in-patients-with-mucopolysaccharidosis-vi-from-turkey
#8
Mustafa Kılıç, Ali Dursun, Turgay Coşkun, Ayşegül Tokatlı, Rıza K Özgül, Didem Yücel-Yılmaz, Mehmet Karaca, Deniz Doğru, Dursun Alehan, Sibel Kadayıfçılar, Aydan Genç, Handan Turan-Dizdar, Burhanettin Gönüldaş, Sema Savcı, Melda Sağlam, Cemalettin Aksoy, Umut Arslan, Hatice-Serap Sivri
Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD) characterized by a chronic, progressive course with multiorgan involvement. In our study, clinical, biochemical, molecular findings, and response to enzyme replacement therapy (ERT) for at least 6 months were evaluated in 20 patients with MPS VI. Treatment effects on clinical findings such as liver and spleen sizes, cardiac and respiratory parameters, visual and auditory changes, joints' range of motions, endurance tests and changes in urinary glycosaminoglycan excretions, before and after ERT were analyzed...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884947/confirmation-of-an-arid2-defect-in-swi-snf-related-intellectual-disability
#9
Ruben Van Paemel, Pauline De Bruyne, Saskia van der Straaten, Marleen D'hondt, Urlien Fränkel, Annelies Dheedene, Björn Menten, Bert Callewaert
We present a 4-year-old girl with delayed neuromotor development, short stature of prenatal onset, and specific behavioral and craniofacial features harboring an intragenic deletion in the ARID2 gene. The phenotype confirmed the major features of the recently described ARID2-related intellectual disability syndrome. However, our patient showed overlapping features with Nicolaides-Baraitser syndrome and Coffin-Siris syndrome, providing further arguments to reclassify these disorders as "SWI/SNF-related intellectual disability syndromes...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884940/variable-phenotypic-expression-in-a-large-noonan-syndrome-family-segregating-a-novel-sos1-mutation
#10
Dorothée C van Trier, Tuula Rinne, Kees Noordam, Jos M Draaisma, Ineke van der Burgt
Noonan syndrome (NS) is an autosomal dominant multisystem condition with a variable phenotype. The most characteristic features are short stature, congenital heart defects, and recognizable facial features. Mutations in SOS1 are found in 10-20% of patients with NS. Different genotype-phenotype studies mention correlations between SOS1 mutations and some features, such as ectodermal abnormalities and specific facial features. We present a large NS family with a novel pathogenic mutation; SOS1 c.3134C>G, p...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884927/peeling-skin-syndrome-associated-with-novel-variant-in-flg2-gene
#11
Ahmed Alfares, Sultan Al-Khenaizan, Fuad Al Mutairi
Peeling skin syndrome is a rare genodermatosis characterized by variably pruritic superficial generalized peeling of the skin with several genes involved until now little is known about the association between FLG2 and peeling skin syndrome. We describe multiple family members from a consanguineous Saudi family with peeling skin syndrome. Next Generation Sequencing identifies a cosegregating novel variant in FLG2 c.632C>G (p.Ser211*) as a likely etiology in this family. Here, we reported on the clinical manifestation of homozygous loss of function variant in FLG2 as a disease-causing gene for peeling skin syndrome and expand the dermatology findings...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884924/two-novel-mutations-in-xylt2-cause-spondyloocular-syndrome
#12
Fulya Taylan, Zehra Yavaş Abalı, Nina Jäntti, Nilay Güneş, Feyza Darendeliler, Firdevs Baş, Şükran Poyrazoğlu, Nevbahar Tamçelik, Beyhan Tüysüz, Outi Mäkitie
We report on two new patients with spondyloocular syndrome. Both patients harbor novel homozygous mutations in the XYLT2 gene. The patients present severe generalized osteoporosis, multiple fractures, short stature, cataract, and mild hearing impairment. XYLT2 mutations have been identified in spondyloocular syndrome, however only five mutations have been reported previously. These two patients with novel mutations extend the phenotypic and genotypic spectrum of spondyloocular syndrome.
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884922/congenital-heart-defects-in-molecularly-proven-kabuki-syndrome-patients
#13
Maria Cristina Digilio, Maria Gnazzo, Francesca Lepri, Maria Lisa Dentici, Elisa Pisaneschi, Anwar Baban, Chiara Passarelli, Rossella Capolino, Adriano Angioni, Antonio Novelli, Bruno Marino, Bruno Dallapiccola
The prevalence of congenital heart defects (CHD) in Kabuki syndrome ranges from 28% to 80%. Between January 2012 and December 2015, 28 patients had a molecularly proven diagnosis of Kabuki syndrome. Pathogenic variants in KMT2D (MLL2) were detected in 27 patients, and in KDM6A gene in one. CHD was diagnosed in 19/27 (70%) patients with KMT2D (MLL2) variant, while the single patient with KDM6A change had a normal heart. The anatomic types among patients with CHD included aortic coarctation (4/19 = 21%) alone or associated with an additional CHD, bicuspid aortic valve (4/19 = 21%) alone or associated with an additional CHD, perimembranous subaortic ventricular septal defect (3/19 = 16%), atrial septal defect ostium secundum type (3/19 = 16%), conotruncal heart defects (3/19 = 16%)...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884921/survival-beyond-the-perinatal-period-expands-the-phenotypes-caused-by-mutations-in-gle1
#14
Edith Said, Jessica X Chong, Maja Hempel, Jonas Denecke, Paul Soler, Tim Strom, Deborah A Nickerson, Christian Kubisch, Michael J Bamshad, Davor Lessel
Mutations in GLE1 underlie Lethal Congenital Contracture syndrome (LCCS) and Lethal Arthrogryposis with Anterior Horn Cell Disease (LAAHD). Both LCCS and LAAHD are characterized by reduced fetal movements, congenital contractures, and a severe form of motor neuron disease that results in fetal death or death in the perinatal period, respectively. We identified bi-allelic mutations in GLE1 in two unrelated individuals with motor delays, feeding difficulties, and respiratory insufficiency who survived beyond the perinatal period...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884893/chimerism-for-20q11-2-microdeletion-of-gdf5-explains-discordant-phenotypes-in-monochorionic-diamniotic-twins
#15
Matthew M Meredith, Beau Crabb, Marcelo Vargas, Betsy A Hirsch
Microdeletions of 20q11.2 are rare but have been associated with characteristic clinical findings. A 1.6 Mb minimal critical region has been identified that includes three OMIM genes: GDF5, EPB41L1, and SAMHD. Here we describe a male monozygotic, monochorionic-diamniotic twin pair with discordant phenotypes, one with multiple findings that overlap with those reported in 20q11.2 deletions, and the other unaffected. Microarray analysis revealed mosaicism for a 363 Kb deletion encompassing GDF5 in the peripheral blood of both twins, which was confirmed by FISH...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884889/novel-homozygous-missense-mutation-in-nt5c2-underlying-hereditary-spastic-paraplegia-spg45
#16
Rachel Straussberg, Alexandros Onoufriadis, Osnat Konen, Yasmin Zouabi, Lior Cohen, John Y W Lee, Chao-Kai Hsu, Michael A Simpson, John A McGrath
SPG45 is a rare form of autosomal recessive spastic paraplegia associated with mental retardation. Detailed phenotyping and mutation analysis was undertaken in three individuals with SPG45 from a consanguineous family of Arab Muslim origin. Using whole-exome sequencing, we identified a novel homozygous missense mutation in NT5C2 (c.1379T>C; p.Leu460Pro). Our data expand the molecular basis of SPG45, adding the first missense mutation to the current database of nonsense, frameshift, and splice site mutations...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884888/foxp1-haploinsufficiency-phenotypes-beyond-behavior-and-intellectual-disability
#17
Angela Myers, Christèle du Souich, Connie L Yang, Lior Borovik, Jill Mwenifumbo, Rosemarie Rupps, Causes Study, Anna Lehman, Cornelius F Boerkoel
The forkhead box (FOX) transcription factors have roles in development, carcinogenesis, metabolism, and immunity. In humans FOXP1 mutations have been associated with language and speech defects, intellectual disability, autism spectrum disorder, facial dysmorphisms, and congenital anomalies of the kidney and urinary tract. In mice, Foxp1 plays critical roles in development of the spinal motor neurons, lymphocytes, cardiomyocytes, foregut, and skeleton. We hypothesized therefore that mutations of FOXP1 affect additional tissues in some humans...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28884880/a-novel-missense-variant-in-the-gli3-zinc-finger-domain-in-a-family-with-digital-anomalies
#18
J Aaron Crapster, Louanne Hudgins, James K Chen, Natalia Gomez-Ospina
Mutations in GLI3, which encodes a transcription factor of the Hedgehog signaling pathway, cause several developmental anomalies linked to inappropriate tissue patterning. Here, we report a novel missense variant in the fifth zinc finger domain of GLI3 (c.1826G>A; p.(Cys609Tyr)) initially identified in a proband with preaxial polydactyly type IV, developmental delay, sensorineural hearing loss, skeletal, and genitourinary anomalies. Additional family members exhibited various digital anomalies such as preaxial polydactyly, syndactyly, and postaxial polydactyly either in isolation or combined...
September 8, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28857390/challenges-in-measuring-the-effects-of-pharmacological-interventions-on-cognitive-and-adaptive-functioning-in-individuals-with-down-syndrome-a-systematic-review
#19
REVIEW
Lori A Keeling, Gail A Spiridigliozzi, Sarah J Hart, Jane A Baker, Harrison N Jones, Priya S Kishnani
We systematically reviewed the measures used in pharmaceutical trials in children/adults with Down syndrome without dementia. Our purpose was to identify developmentally appropriate outcome measures capable of detecting changes in cognitive and adaptive functioning in this population. Eleven studies were included and used diverse outcome measures across the domains of language, memory, attention, behavior, and executive/adaptive functioning. Our results highlight the challenges in selecting measures capable of capturing improvements in pharmaceutical trials in individuals with DS...
August 31, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28856870/factors-related-to-home-health-care-transition-in-trisomy-13
#20
Yuma Kitase, Masahiro Hayakawa, Taiki Kondo, Akiko Saito, Takashi Tachibana, Makoto Oshiro, Kuniko Ieda, Eiko Kato, Yuichi Kato, Tetsuo Hattori, Seiji Hayashi, Masatoki Ito, Reina Hyodo, Yukako Muramatsu, Yoshiaki Sato
Trisomy 13 (T13) is accompanied by severe complications, and it can be challenging to achieve long-term survival without aggressive treatment. However, recently, some patients with T13 have been receiving home care. We conducted this study to investigate factors related to home health-care transition for patients with T13.We studied 28 patients with T13 born between January 2000 and December 2014. We retrospectively compared nine home care transition patients (the home care group) and 19 patients that died during hospitalization (the discharge at death group)...
August 29, 2017: American Journal of Medical Genetics. Part A
journal
journal
40910
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"