@article {909, title = {Deciphering congenital anomalies for the next generation.}, journal = {Cold Spring Harb Mol Case Stud}, volume = {6}, year = {2020}, month = {2020 10}, abstract = {

Congenital anomalies are common, with 2\%-3\% of infants estimated to have at least one major congenital malformation and countless others with minor malformations of lesser cosmetic or medical importance. As congenital malformations are major drivers of morbidity and mortality, representing the leading cause of infant mortality in the United States, there is substantial interest in understanding the underlying etiologies-particularly if modifiable causes may be identified or pre- or postnatal treatments can be offered. Recent research has begun to reveal the spectrum of monogenic disorders that commonly result in birth defects, and newer approaches have revealed non-Mendelian genetic contributions including gene-environment interactions. Our experience suggests that increased efforts to sequence and analyze cases of perinatal death, as well as continued global collaboration, will be essential in understanding the genomic landscape of structural anomalies.

}, keywords = {Congenital Abnormalities, Family Characteristics, Female, Humans, Infant, Pregnancy}, issn = {2373-2873}, doi = {10.1101/mcs.a005504}, author = {Wojcik, Monica H and Agrawal, Pankaj B} } @article {822, title = {Gene-based analyses of the maternal genome implicate maternal effect genes as risk factors for conotruncal heart defects.}, journal = {PLoS One}, volume = {15}, year = {2020}, month = {2020}, pages = {e0234357}, abstract = {

Congenital heart defects (CHDs) affect approximately 1\% of newborns. Epidemiological studies have identified several genetically-mediated maternal phenotypes (e.g., pregestational diabetes, chronic hypertension) that are associated with the risk of CHDs in offspring. However, the role of the maternal genome in determining CHD risk has not been defined. We present findings from gene-level, genome-wide studies that link CHDs to maternal effect genes as well as to maternal genes related to hypertension and proteostasis. Maternal effect genes, which provide the mRNAs and proteins in the oocyte that guide early embryonic development before zygotic gene activation, have not previously been implicated in CHD risk. Our findings support a role for and suggest new pathways by which the maternal genome may contribute to the development of CHDs in offspring.

}, keywords = {Adult, Case-Control Studies, Child, Preschool, Family, Female, Genetic Testing, Heart Defects, Congenital, Humans, Hypertension, Infant, Infant, Newborn, Male, Maternal Exposure, Maternal Inheritance, Middle Aged, Oocytes, Pregnancy, Prenatal Exposure Delayed Effects, Proteostasis, Risk Factors}, issn = {1932-6203}, doi = {10.1371/journal.pone.0234357}, author = {Sewda, Anshuman and Agopian, A J and Goldmuntz, Elizabeth and Hakonarson, Hakon and Morrow, Bernice E and Musfee, Fadi and Taylor, Deanne and Mitchell, Laura E} } @article {826, title = {Molecular diagnosis in recessive pediatric neurogenetic disease can help reduce disease recurrence in families.}, journal = {BMC Med Genomics}, volume = {13}, year = {2020}, month = {2020 05 13}, pages = {68}, abstract = {

BACKGROUND: The causes for thousands of individually rare recessive diseases have been discovered since the adoption of next generation sequencing (NGS). Following the molecular diagnosis in older children in a family, parents could use this information to opt for fetal genotyping in subsequent pregnancies, which could inform decisions about elective termination of pregnancy. The use of NGS diagnostic sequencing in families has not been demonstrated to yield benefit in subsequent pregnancies to reduce recurrence. Here we evaluated whether genetic diagnosis in older children in families supports reduction in recurrence of recessive neurogenetic disease.

METHODS: Retrospective study involving families with a child with a recessive pediatric brain disease (rPBD) that underwent NGS-based molecular diagnosis. Prenatal molecular testing was offered to couples in which a molecular diagnosis was made, to help couples seeking to prevent recurrence. With this information, families made decisions about elective termination. Pregnancies that were carried to term were assessed for the health of child and mother, and compared with historic recurrence risk of recessive disease.

RESULTS: Between 2010 and 2016, 1172 families presented with a child a likely~rPBD, 526 families received a molecular diagnosis, 91 families returned to the clinic with 101 subsequent pregnancies, and 84 opted for fetal genotyping. Sixty tested negative for recurrence for the biallelic mutation~in the fetus, and all, except for one spontaneous abortion, carried to term, and were unaffected at follow-up. Of 24 that genotyped positive~for~the biallelic mutation, 16 were electively terminated, and 8 were carried to term and showed features of disease similar to that of the older~affected sibling(s). Among the 101 pregnancies, disease recurrence in living offspring deviated from the expected 25\% to the observed 12\% ([95\% CI 0{\textperiodcentered}04 to 0{\textperiodcentered}20], p = 0{\textperiodcentered}011).

CONCLUSIONS: Molecular diagnosis in an older child, coupled with prenatal fetal genotyping in subsequent pregnancies and genetic counselling, allows families to make informed decisions to reduce recessive neurogenetic disease recurrence.

}, keywords = {Child, Preschool, Female, Genes, Recessive, Genetic Markers, Genetic Predisposition to Disease, Genetic Testing, Genotype, High-Throughput Nucleotide Sequencing, Humans, Infant, Infant, Newborn, Male, Mutation, Nervous System Diseases, Pedigree, Pregnancy, Prenatal Diagnosis, Recurrence, Retrospective Studies}, issn = {1755-8794}, doi = {10.1186/s12920-020-0714-1}, author = {Issa, Mahmoud Y and Chechlacz, Zinayida and Stanley, Valentina and George, Renee D and McEvoy-Venneri, Jennifer and Belandres, Denice and Elbendary, Hasnaa M and Gaber, Khaled R and Nabil, Ahmed and Abdel-Hamid, Mohamed S and Zaki, MAH S and Gleeson, Joseph G} } @article {751, title = {Paternal mosaicism for a novel PBX1 mutation associated with recurrent perinatal death: Phenotypic expansion of the PBX1-related syndrome.}, journal = {Am J Med Genet A}, volume = {182}, year = {2020}, month = {2020 05}, pages = {1273-1277}, abstract = {

Autosomal dominant (de novo) mutations in PBX1 are known to cause congenital abnormalities of the kidney and urinary tract (CAKUT), with or without extra-renal abnormalities. Using trio exome sequencing, we identified a PBX1 p.(Arg107Trp) mutation in a deceased one-day-old neonate presenting with CAKUT, asplenia, and severe bilateral diaphragmatic thinning and eventration. Further investigation by droplet digital PCR revealed that the mutation had occurred post-zygotically in the father, with different variant allele frequencies of the mosaic PBX1 mutation in blood (10\%) and sperm (20\%). Interestingly, the father had subclinical hydronephrosis in childhood. With an expected recurrence risk of one in five, chorionic villus sampling and prenatal diagnosis for the PBX1 mutation identified recurrence in a subsequent pregnancy. The family opted to continue the pregnancy and the second affected sibling was stillborn at 35 weeks, presenting with similar severe bilateral diaphragmatic eventration, microsplenia, and complete sex reversal (46, XY female). This study highlights the importance of follow-up studies for presumed de novo and low-level mosaic variants and broadens the phenotypic spectrum of developmental abnormalities caused by PBX1 mutations.

}, keywords = {Congenital Abnormalities, Exome, Fathers, Female, Gene Frequency, Humans, Infant, Newborn, Kidney, Male, Mosaicism, Mutation, Perinatal Death, Pre-B-Cell Leukemia Transcription Factor 1, Pregnancy, Urinary Tract, Urogenital Abnormalities, Whole Exome Sequencing}, issn = {1552-4833}, doi = {10.1002/ajmg.a.61541}, author = {Arts, Peer and Garland, Jessica and Byrne, Alicia B and Hardy, Tristan S E and Babic, Milena and Feng, Jinghua and Wang, Paul and Ha, Thuong and King-Smith, Sarah L and Schreiber, Andreas W and Crawford, April and Manton, Nick and Moore, Lynette and Barnett, Christopher P and Scott, Hamish S} } @article {760, title = {Prenatal Diagnosis of a Ventral Abdominal Wall Defect.}, journal = {Neoreviews}, volume = {21}, year = {2020}, month = {2020 04}, pages = {e286-e292}, keywords = {Abnormalities, Multiple, Echocardiography, Fatal Outcome, Female, Hernia, Abdominal, Hernia, Diaphragmatic, Hernia, Ventral, Humans, Infant, Newborn, Magnetic Resonance Imaging, Pregnancy, Prenatal Diagnosis, Ultrasonography, Prenatal}, issn = {1526-9906}, doi = {10.1542/neo.21-4-e286}, author = {Beam, Kristyn and Wojcik, Monica H and Agrawal, Pankaj B and Smithers, Charles and Estroff, Judy} } @article {465, title = {The role of FREM2 and FRAS1 in the development of congenital diaphragmatic hernia.}, journal = {Hum Mol Genet}, volume = {27}, year = {2018}, month = {2018 06 15}, pages = {2064-2075}, abstract = {

Congenital diaphragmatic hernia (CDH) has been reported twice in individuals with a clinical diagnosis of Fraser syndrome, a genetic disorder that can be caused by recessive mutations affecting FREM2 and FRAS1. In the extracellular matrix, FREM2 and FRAS1 form a self-stabilizing complex with FREM1, a protein whose deficiency causes sac CDH in humans and mice. By sequencing FREM2 and FRAS1 in a CDH cohort, and searching online databases, we identified five individuals who carried recessive or double heterozygous, putatively deleterious variants in these genes which may represent susceptibility alleles. Three of these alleles were significantly enriched in our CDH cohort compared with ethnically matched controls. We subsequently demonstrated that 8\% of Frem2ne/ne and 1\% of Fras1Q1263*/Q1263* mice develop the same type of anterior sac CDH seen in FREM1-deficient mice. We went on to show that development of sac hernias in FREM1-deficient mice is preceded by failure of anterior mesothelial fold progression resulting in the persistence of an amuscular, poorly vascularized anterior diaphragm that is abnormally adherent to the underlying liver. Herniation occurs in the perinatal period when the expanding liver protrudes through this amuscular region of the anterior diaphragm that is juxtaposed to areas of muscular diaphragm. Based on these data, we conclude that deficiency of FREM2, and possibly FRAS1, are associated with an increased risk of developing CDH and that loss of the FREM1/FREM2/FRAS1 complex, or its function, leads to anterior sac CDH development through its effects on mesothelial fold progression.

}, keywords = {Animals, Child, Child, Preschool, Epithelium, Extracellular Matrix Proteins, Female, Hernias, Diaphragmatic, Congenital, Humans, Infant, Infant, Newborn, Male, Mice, Mice, Knockout, Mutation, Pregnancy, Receptors, Interleukin}, issn = {1460-2083}, doi = {10.1093/hmg/ddy110}, author = {Jordan, Valerie K and Beck, Tyler F and Hernandez-Garcia, Andres and Kundert, Peter N and Kim, Bum-Jun and Jhangiani, Shalini N and Gambin, Tomasz and Starkovich, Molly and Punetha, Jaya and Paine, Ingrid S and Posey, Jennifer E and Li, Alexander H and Muzny, Donna and Hsu, Chih-Wei and Lashua, Amber J and Sun, Xin and Fernandes, Caraciolo J and Dickinson, Mary E and Lally, Kevin P and Gibbs, Richard A and Boerwinkle, Eric and Lupski, James R and Scott, Daryl A} } @article {409, title = {Mutations in DYNC2H1, the cytoplasmic dynein 2, heavy chain 1 motor protein gene, cause short-rib polydactyly type I, Saldino-Noonan type.}, journal = {Clin Genet}, volume = {92}, year = {2017}, month = {2017 Aug}, pages = {158-165}, abstract = {

The short-rib polydactyly syndromes (SRPS) are autosomal recessively inherited, genetically heterogeneous skeletal ciliopathies. SRPS phenotypes were historically categorized as types I-IV, with type I first delineated by Saldino and Noonan in 1972. Characteristic findings among all forms of SRP include short horizontal ribs, short limbs and polydactyly. The SRP type I phenotype is characterized by a very small thorax, extreme micromelia, very short, poorly mineralized long bones, and multiple organ system anomalies. To date, the molecular basis of this most severe type of SRP, also known as Saldino-Noonan syndrome, has not been determined. We identified three SRP cases that fit the original phenotypic description of SRP type I. In all three cases, exome sequence analysis revealed compound heterozygosity for mutations in DYNC2H1, which encodes the main component of the retrograde IFT A motor, cytoplasmic dynein 2 heavy chain 1. Thus SRP type I, II, III and asphyxiating thoracic dystrophy (ATD), which also result from DYNC2H1 mutations. Herein we describe the phenotypic features, radiographic findings, and molecular basis of SRP type I.

}, keywords = {Cytoplasmic Dyneins, Ellis-Van Creveld Syndrome, Female, Fetus, Genetic Heterogeneity, Genetic Predisposition to Disease, Humans, Infant, Newborn, Mutation, Phenotype, Pregnancy, Radiography, Short Rib-Polydactyly Syndrome, Whole Exome Sequencing}, issn = {1399-0004}, doi = {10.1111/cge.12947}, author = {Badiner, N and Taylor, S P and Forlenza, K and Lachman, R S and Bamshad, M and Nickerson, D and Cohn, D H and Krakow, D} } @article {378, title = {Survival beyond the perinatal period expands the phenotypes caused by mutations in GLE1.}, journal = {Am J Med Genet A}, volume = {173}, year = {2017}, month = {2017 Nov}, pages = {3098-3103}, abstract = {

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. Each affected child had missense variants predicted to result in amino acid substitutions near the C-terminus of GLE1 that are predicted to disrupt protein-protein interaction or GLE1 protein targeting. We hypothesize that mutations that preserve function of the coiled-coil domain of GLE1 cause LAAHD whereas mutations that abolish the function of the coiled-coil domain cause LCCS. The phenotype of LAAHD is now expanded to include multiple individuals surviving into childhood suggesting that LAAHD is a misnomer and should be re-named Arthrogryposis with Anterior Horn Cell Disease (AAHD).

}, keywords = {Arthrogryposis, Child, Preschool, Female, Genetic Predisposition to Disease, Humans, Male, Motor Disorders, Motor Neuron Disease, Mutation, Nucleocytoplasmic Transport Proteins, Pedigree, Pregnancy}, issn = {1552-4833}, doi = {10.1002/ajmg.a.38406}, author = {Said, Edith and Chong, Jessica X and Hempel, Maja and Denecke, Jonas and Soler, Paul and Strom, Tim and Nickerson, Deborah A and Kubisch, Christian and Bamshad, Michael J and Lessel, Davor} } @article {26, title = {Collapsing glomerulopathy in a young woman with APOL1 risk alleles following acute parvovirus B19 infection: a case report investigation.}, journal = {BMC Nephrol}, volume = {17}, year = {2016}, month = {2016 Sep 06}, pages = {125}, abstract = {

BACKGROUND: Collapsing Glomerulopathy (CG), also known as the collapsing variant of Focal Segmental Glomerulosclerosis (FSGS), is distinct in both its clinical severity and its pathophysiologic characteristics from other forms of FSGS. This lesion occurs disproportionally in patients carrying two APOL1 risk alleles, and is the classic histologic lesion resulting from Human Immunodeficiency Virus (HIV) infection of podocytes. Other viral infections, including parvovirus B19, and drugs such as interferon that perturb the immune system, have also been associated with CG. Despite significant advances, explaining such genetic and immune/infectious associations with causative mechanisms and supporting evidence has proven challenging.

CASE PRESENTATION: We report the case of a healthy (HIV-negative) pregnant 36~year-old Caribbean-American woman who presented with nephrotic syndrome and fetal demise in the setting of acute parvovirus B19 infection. A series of three renal biopsies and rapid clinical course showed progression from significant podocyte injury with mild light microscopy findings to classic viral-associated CG to ESRD in less than 3~months. Genetic analysis revealed two APOL1 G1 risk alleles.

CONCLUSIONS: This is the first published case report of CG in the setting of acute parvovirus infection in a patient with two APOL1 risk allelles, and parvoviral proteins identified in renal epithelium on kidney biopsy. These findings support the causative role of parvovirus B19 infection in the development of CG on the background of APOL1 genetic risk.

}, keywords = {Acute Disease, Adult, Alleles, Apolipoprotein L1, Female, Glomerulosclerosis, Focal Segmental, Humans, Kidney Failure, Chronic, Parvoviridae Infections, Parvovirus B19, Human, Pregnancy, Pregnancy Complications, Infectious}, issn = {1471-2369}, doi = {10.1186/s12882-016-0330-7}, author = {Besse, Whitney and Mansour, Sherry and Jatwani, Karan and Nast, Cynthia C and Brewster, Ursula C} } @article {343, title = {An inactivating mutation in intestinal cell kinase, ICK, impairs hedgehog signalling and causes short rib-polydactyly syndrome.}, journal = {Hum Mol Genet}, volume = {25}, year = {2016}, month = {2016 09 15}, pages = {3998-4011}, abstract = {

The short rib polydactyly syndromes (SRPS) are a group of recessively inherited, perinatal-lethal skeletal disorders primarily characterized by short ribs, shortened long bones, varying types of polydactyly and concomitant visceral abnormalities. Mutations in several genes affecting cilia function cause SRPS, revealing a role for cilia function in skeletal development. To identify additional SRPS genes and discover novel ciliary molecules required for normal skeletogenesis, we performed exome sequencing in a cohort of patients and identified homozygosity for a missense mutation, p.E80K, in Intestinal Cell Kinase, ICK, in one SRPS family. The p.E80K mutation abolished serine/threonine kinase activity, resulting in altered ICK subcellular and ciliary localization, increased cilia length, aberrant cartilage growth plate structure, defective Hedgehog and altered ERK signalling. These data identify ICK as an SRPS-associated gene and reveal that abnormalities in signalling pathways contribute to defective skeletogenesis.

}, keywords = {Abnormalities, Multiple, Cilia, Exome, Female, Hedgehog Proteins, Humans, Infant, MAP Kinase Signaling System, Pedigree, Pregnancy, Protein-Serine-Threonine Kinases, Sequence Analysis, DNA, Short Rib-Polydactyly Syndrome, Signal Transduction, Skeleton}, issn = {1460-2083}, doi = {10.1093/hmg/ddw240}, author = {Paige Taylor, S and Kunova Bosakova, Michaela and Varecha, Miroslav and Balek, Lukas and Barta, Tomas and Trantirek, Lukas and Jelinkova, Iva and Duran, Ivan and Vesela, Iva and Forlenza, Kimberly N and Martin, Jorge H and Hampl, Ales and Bamshad, Michael and Nickerson, Deborah and Jaworski, Margie L and Song, Jieun and Ko, Hyuk Wan and Cohn, Daniel H and Krakow, Deborah and Krejci, Pavel} } @article {641, title = {An anadysplasia-like, spontaneously remitting spondylometaphyseal dysplasia secondary to lamin B receptor (LBR) gene mutations: further definition of the phenotypic heterogeneity of LBR-bone dysplasias.}, journal = {Am J Med Genet A}, volume = {167A}, year = {2015}, month = {2015 Jan}, pages = {159-63}, abstract = {

We describe a boy who has an anadysplasia-like spondylometaphyseal dysplasia. By whole exome sequencing he was shown to have compound heterozygous mutations of LBR that codes for the lamin B receptor. He shares many similarities with a case previously described, but in whom the early natural history could not be established [Borovik et al., 2013]. Thus, in addition to Greenberg dysplasia (a perinatal lethal disorder), homozygosity or compound heterozygosity of mutations in LBR can result in a mild, spontaneously regressing bone dysplasia.

}, keywords = {Adolescent, Adult, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Mutation, Osteochondrodysplasias, Phenotype, Pregnancy, Radiography, Receptors, Cytoplasmic and Nuclear, Spine}, issn = {1552-4833}, doi = {10.1002/ajmg.a.36808}, author = {Sobreira, Nara and Modaff, Peggy and Steel, Gary and You, Jing and Nanda, Sonia and Hoover-Fong, Julie and Valle, David and Pauli, Richard M} } @article {240, title = {Diamond-Blackfan anemia with mandibulofacial dystostosis is heterogeneous, including the novel DBA genes TSR2 and RPS28.}, journal = {Am J Med Genet A}, volume = {164A}, year = {2014}, month = {2014 Sep}, pages = {2240-9}, abstract = {

Patients with physical findings suggestive of Treacher Collins syndrome (TCS) or mandibulofacial dysostosis (MFD) and macrocytic anemia diagnostic of Diamond-Blackfan anemia (DBA) have been reported. Disease-causing genes have been identified for TCS and other MFDs. Mutations in several ribosomal protein genes and the transcription factor GATA1 result in DBA. However, no disease-causing mutation had been identified in the reported patients with the combination of TCS/MFD and DBA phenotype, and we hypothesized that pathogenic mutations in a single gene could be identified using whole exome analysis. We studied probands from six unrelated families. Combining exome analysis and Sanger sequencing, we identified likely pathogenic mutations in 5/6 families. Two mutations in unrelated families were seen in RPS26, the known DBA10 gene. One variant was predicted to affect mRNA splicing, and the other to lead to protein truncation. In another family a likely pathogenic X-linked mutation affecting a highly conserved residue was found in TSR2, which encodes a direct binding partner of RPS26. De novo mutations affecting the RPS28 start codon were found in two unrelated probands, identifying RPS28 as a novel disease gene. We conclude that the phenotype combining features of TCS with DBA is genetically heterogeneous. Each of the pathogenic variants identified is predicted to impede ribosome biogenesis, which in turn could result in altered cell growth and proliferation, causing abnormal embryologic development, defective erythropoiesis and reduced growth. The phenotype combining TCS/MFD and DBA is highly variable, overlaps with DBA and lies within the phenotypic spectrum of ribosomopathies. {\textcopyright} 2014 Wiley Periodicals, Inc.

}, keywords = {Adult, Anemia, Diamond-Blackfan, Apoptosis Regulatory Proteins, Child, Preschool, Exome, Family, Female, Genetic Heterogeneity, Humans, Infant, Infant, Newborn, Male, Mandibulofacial Dysostosis, Pedigree, Phenotype, Pregnancy, Ribosomal Proteins, Young Adult}, issn = {1552-4833}, doi = {10.1002/ajmg.a.36633}, author = {Gripp, Karen W and Curry, Cynthia and Olney, Ann Haskins and Sandoval, Claudio and Fisher, Jamie and Chong, Jessica Xiao-Ling and Pilchman, Lisa and Sahraoui, Rebecca and Stabley, Deborah L and Sol-Church, Katia} } @article {222, title = {Parent of origin, mosaicism, and recurrence risk: probabilistic modeling explains the broken symmetry of transmission genetics.}, journal = {Am J Hum Genet}, volume = {95}, year = {2014}, month = {2014 Oct 02}, pages = {345-59}, abstract = {

Most new mutations are observed to arise in fathers, and increasing paternal age positively correlates with the risk of new variants. Interestingly, new mutations in X-linked recessive disease show elevated familial recurrence rates. In male offspring, these mutations must be inherited from mothers. We previously developed a simulation model to consider parental mosaicism as a source of transmitted mutations. In this paper, we extend and formalize the model to provide analytical results and flexible formulas. The results implicate parent of origin and parental mosaicism as central variables in recurrence risk. Consistent with empirical data, our model predicts that more transmitted mutations arise in fathers and that this tendency increases as fathers age. Notably, the lack of expansion later in the male germline determines relatively lower variance in the proportion of mutants, which decreases with paternal age. Subsequently, observation of a transmitted mutation has less impact on the expected risk for future offspring. Conversely, for the female germline, which arrests after clonal expansion in early development, variance in the mutant proportion is higher, and observation of a transmitted mutation dramatically increases the expected risk of recurrence in another pregnancy. Parental somatic mosaicism considerably elevates risk for both parents. These findings have important implications for genetic counseling and for understanding patterns of recurrence in transmission genetics. We provide a convenient online tool and source code implementing our analytical results. These tools permit varying the underlying parameters that influence recurrence risk and could be useful for analyzing risk in diverse family structures.

}, keywords = {Adult, Aged, Aged, 80 and over, Chromosome Aberrations, DNA Copy Number Variations, Fathers, Female, Gametogenesis, Genetic Diseases, Inborn, Genomics, Germ Cells, Germ-Line Mutation, Humans, Inheritance Patterns, Male, Middle Aged, Models, Theoretical, Mosaicism, Mothers, Pregnancy, Recurrence, Risk Factors, Young Adult}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2014.08.010}, author = {Campbell, Ian M and Stewart, Jonathan R and James, Regis A and Lupski, James R and Stankiewicz, Pawe{\l} and Olofsson, Peter and Shaw, Chad A} }