Publications by authors named "Ingrid Scurr"

19 Publications

  • Page 1 of 1

Delineating the Smith-Kingsmore syndrome phenotype: Investigation of 16 patients with the MTOR c.5395G > A p.(Glu1799Lys) missense variant.

Am J Med Genet A 2021 08 25;185(8):2445-2454. Epub 2021 May 25.

St George's University of London, London, UK.

Smith-Kingsmore Syndrome (SKS) is a rare genetic syndrome associated with megalencephaly, a variable intellectual disability, autism spectrum disorder, and MTOR gain of function variants. Only 30 patients with MTOR missense variants are published, including 14 (47%) with the MTOR c.5395G>A p.(Glu1799Lys) variant. Limited phenotypic data impacts the quality of information delivered to families and the robustness of interpretation of novel MTOR missense variation. This study aims to improve our understanding of the SKS phenotype through the investigation of 16 further patients with the MTOR c.5395G>A p.(Glu1799Lys) variant. Through the careful phenotypic evaluation of these 16 patients and integration with data from 14 previously reported patients, we have defined major (100% patients) and frequent (>15%) SKS clinical characteristics and, using these data, proposed guidance for evidence-based management. In addition, in the absence of functional studies, we suggest that the combination of the SKS major clinical features of megalencephaly (where the head circumference is at least 3SD) and an intellectual disability with a de novo MTOR missense variant (absent from population databases) should be considered diagnostic for SKS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.62350DOI Listing
August 2021

Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2.

Genet Med 2021 07 5;23(7):1202-1210. Epub 2021 Mar 5.

Genetic Health Queensland c/-Royal Brisbane and Women's Hospital, Herston, QLD, Australia.

Purpose: The variant spectrum and the phenotype of X-linked Kabuki syndrome type 2 (KS2) are poorly understood.

Methods: Genetic and clinical details of new and published individuals with pathogenic KDM6A variants were compiled and analyzed.

Results: Sixty-one distinct pathogenic KDM6A variants (50 truncating, 11 missense) from 80 patients (34 males, 46 females) were identified. Missense variants clustered in the TRP 2, 3, 7 and Jmj-C domains. Truncating variants were significantly more likely to be de novo. Thirteen individuals had maternally inherited variants and one had a paternally inherited variant. Neonatal feeding difficulties, hypoglycemia, postnatal growth retardation, poor weight gain, motor delay, intellectual disability (ID), microcephaly, congenital heart anomalies, palate defects, renal malformations, strabismus, hearing loss, recurrent infections, hyperinsulinism, seizures, joint hypermobility, and gastroesophageal reflux were frequent clinical findings. Facial features of over a third of patients were not typical for KS. Males were significantly more likely to be born prematurely, have shorter stature, and severe developmental delay/ID.

Conclusion: We expand the KDM6A variant spectrum and delineate the KS2 phenotype. We demonstrate that the variability of the KS2 phenotypic depends on sex and the variant type. We also highlight the overlaps and differences between the phenotypes of KS2 and KS1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-021-01119-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257478PMC
July 2021

Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K channelopathies.

Eur J Hum Genet 2021 Sep 16;29(9):1384-1395. Epub 2021 Feb 16.

Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Decreased or increased activity of potassium channels caused by loss-of-function and gain-of-function (GOF) variants in the corresponding genes, respectively, underlies a broad spectrum of human disorders affecting the central nervous system, heart, kidney, and other organs. While the association of epilepsy and intellectual disability (ID) with variants affecting function in genes encoding potassium channels is well known, GOF missense variants in K channel encoding genes in individuals with syndromic developmental disorders have only recently been recognized. These syndromic phenotypes include Zimmermann-Laband and Temple-Baraitser syndromes, caused by dominant variants in KCNH1, FHEIG syndrome due to dominant variants in KCNK4, and the clinical picture associated with dominant variants in KCNN3. Here we review the presentation of these individuals, including five newly reported with variants in KCNH1 and three additional individuals with KCNN3 variants, all variants likely affecting function. There is notable overlap in the phenotypic findings of these syndromes associated with dominant KCNN3, KCNH1, and KCNK4 variants, sharing developmental delay and/or ID, coarse facial features, gingival enlargement, distal digital hypoplasia, and hypertrichosis. We suggest to combine the phenotypes and define a new subgroup of potassium channelopathies caused by increased K conductance, referred to as syndromic neurodevelopmental K channelopathies due to dominant variants in KCNH1, KCNK4, or KCNN3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41431-021-00818-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440610PMC
September 2021

Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism.

Am J Hum Genet 2020 02 30;106(2):272-279. Epub 2020 Jan 30.

Exeter Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter EX2 5DW, UK; Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter EX2 5DW, UK. Electronic address:

Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis of the breakpoint junction fragment indicated that these 67 kb heterozygous duplications were likely mediated by non-allelic homologous recombination at regions of high sequence identity in ATAD3A exon 11 and ATAD3C exon 7. At the recombinant junction, the duplication allele produces a fusion gene derived from ATAD3A and ATAD3C, the protein product of which lacks key functional residues. Analysis of fibroblasts derived from two affected individuals shows that the fusion gene product is expressed and stable. These cells display perturbed cholesterol and mitochondrial DNA organization similar to that observed for individuals with severe ATAD3A deficiency. We hypothesize that the fusion protein acts through a dominant-negative mechanism to cause this fatal mitochondrial disorder. Our data delineate a molecular diagnosis for this disorder, extend the clinical spectrum associated with structural variation at the ATAD3 locus, and identify a third mutational mechanism for ATAD3 gene cluster variants. These results further affirm structural variant mutagenesis mechanisms in sporadic disease traits, emphasize the importance of copy number analysis in molecular genomic diagnosis, and highlight some of the challenges of detecting and interpreting clinically relevant rare gene rearrangements from next-generation sequencing data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010973PMC
February 2020

Cantú syndrome: Findings from 74 patients in the International Cantú Syndrome Registry.

Am J Med Genet C Semin Med Genet 2019 12;181(4):658-681

Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Cantú syndrome (CS), first described in 1982, is caused by pathogenic variants in ABCC9 and KCNJ8, which encode the regulatory and pore forming subunits of ATP-sensitive potassium (K ) channels, respectively. Multiple case reports of affected individuals have described the various clinical features of CS, but systematic studies are lacking. To define the effects of genetic variants on CS phenotypes and clinical outcomes, we have developed a standardized REDCap-based registry for CS. We report phenotypic features and associated genotypes on 74 CS subjects, with confirmed ABCC9 variants in 72 of the individuals. Hypertrichosis and a characteristic facial appearance are present in all individuals. Polyhydramnios during fetal life, hyperflexibility, edema, patent ductus arteriosus (PDA), cardiomegaly, dilated aortic root, vascular tortuosity of cerebral arteries, and migraine headaches are common features, although even with this large group of subjects, there is incomplete penetrance of CS-associated features, without clear correlation to genotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.c.31753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654223PMC
December 2019

Exome sequencing in patients with antiepileptic drug exposure and complex phenotypes.

Arch Dis Child 2020 04 3;105(4):384-389. Epub 2019 Sep 3.

Genetic Medicine, Central Manchester University Hospitals Foundation Trust, Manchester, UK.

Introduction: Fetal anticonvulsant syndrome (FACS) describes the pattern of physical and developmental problems seen in those children exposed to certain antiepileptic drugs (AEDs) in utero. The diagnosis of FACS is a clinical one and so excluding alternative diagnoses such as genetic disorders is essential.

Methods: We reviewed the pathogenicity of reported variants identified on exome sequencing in the Deciphering Developmental Disorders (DDD) Study in 42 children exposed to AEDs in utero, but where a diagnosis other than FACS was suspected. In addition, we analysed chromosome microarray data from 10 patients with FACS seen in a Regional Genetics Service.

Results: Seven children (17%) from the DDD Study had a copy number variant or pathogenic variant in a developmental disorder gene which was considered to explain or partially explain their phenotype. Across the AED exposure types, variants were found in 2/15 (13%) valproate exposed cases and 3/14 (21%) carbamazepine exposed cases. No pathogenic copy number variants were identified in our local sample (n=10).

Conclusions: This study is the first of its kind to analyse the exomes of children with developmental disorders who were exposed to AEDs in utero. Though we acknowledge that the results are subject to bias, a significant number of children were identified with alternate diagnoses which had an impact on counselling and management. We suggest that consideration is given to performing whole exome sequencing as part of the diagnostic work-up for children exposed to AEDs in utero.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2018-316547DOI Listing
April 2020

Compound heterozygous Pkd1l1 variants in a family with two fetuses affected by heterotaxy and complex Chd.

Eur J Med Genet 2020 Feb 23;63(2):103657. Epub 2019 Apr 23.

Department of Clinical Genetics, University Hospitals Bristol, Bristol, UK. Electronic address:

Heterotaxy and congenital heart defects associated with pathogenic variants in the PKD1L1 gene (autosomal visceral heterotaxy type 8, MIM 617205) has been reported in only four individuals from three unrelated families. We describe a further family with two affected fetuses and novel compound heterozygous pathogenic variants in PKD1L1. PKD1L1 has been shown to function in the ciliary sensation of nodal flow at the embryo primitive node and in the restriction of NODAL signalling to the left lateral. plate mesoderm, mechanisms involved in the development of laterality in vertebrates. Individuals affected with this autosomal recessive condition have variable thoracic and abdominal situs. Features of CHD and other anomalies vary between and within families.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmg.2019.04.014DOI Listing
February 2020

KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants.

Genet Med 2019 04 24;21(4):850-860. Epub 2018 Sep 24.

Service de Génétique Médicale, CHU Nantes, Nantes, France.

Purpose: Pathogenic variants in KAT6A have recently been identified as a cause of syndromic developmental delay. Within 2 years, the number of patients identified with pathogenic KAT6A variants has rapidly expanded and the full extent and variability of the clinical phenotype has not been reported.

Methods: We obtained data for patients with KAT6A pathogenic variants through three sources: treating clinicians, an online family survey distributed through social media, and a literature review.

Results: We identified 52 unreported cases, bringing the total number of published cases to 76. Our results expand the genotypic spectrum of pathogenic variants to include missense and splicing mutations. We functionally validated a pathogenic splice-site variant and identified a likely hotspot location for de novo missense variants. The majority of clinical features in KAT6A syndrome have highly variable penetrance. For core features such as intellectual disability, speech delay, microcephaly, cardiac anomalies, and gastrointestinal complications, genotype- phenotype correlations show that late-truncating pathogenic variants (exons 16-17) are significantly more prevalent. We highlight novel associations, including an increased risk of gastrointestinal obstruction.

Conclusion: Our data expand the genotypic and phenotypic spectrum for individuals with genetic pathogenic variants in KAT6A and we outline appropriate clinical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-018-0259-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634310PMC
April 2019

Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency: is riboflavin supplementation effective?

Orphanet J Rare Dis 2018 07 19;13(1):120. Epub 2018 Jul 19.

Child Neurology, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.

Background: Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individuals presenting with lactic acidosis and cardiomyopathy.

Results: We describe the genetic, clinical and biochemical findings in a cohort of 70 patients, of whom 29 previously unpublished. We found 34 known and 18 previously unreported variants in ACAD9. No patients harbored biallelic loss of function mutations, indicating that this combination is unlikely to be compatible with life. Causal pathogenic variants were distributed throughout the entire gene, and there was no obvious genotype-phenotype correlation. Most of the patients presented in the first year of life. For this subgroup the survival was poor (50% not surviving the first 2 years) comparing to patients with a later presentation (more than 90% surviving 10 years). The most common clinical findings were cardiomyopathy (85%), muscular weakness (75%) and exercise intolerance (72%). Interestingly, severe intellectual deficits were only reported in one patient and severe developmental delays in four patients. More than 70% of the patients were able to perform the same activities of daily living when compared to peers.

Conclusions: Our data show that riboflavin treatment improves complex I activity in the majority of patient-derived fibroblasts tested. This effect was also reported for most of the treated patients and is mirrored in the survival data. In the patient group with disease-onset below 1 year of age, we observed a statistically-significant better survival for patients treated with riboflavin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13023-018-0784-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053715PMC
July 2018

Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort.

Hum Mutat 2018 09 4;39(9):1246-1261. Epub 2018 Jul 4.

Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.

Adams-Oliver syndrome (AOS) is a rare developmental disorder, characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Autosomal dominant forms of AOS are linked to mutations in ARHGAP31, DLL4, NOTCH1 or RBPJ, while DOCK6 and EOGT underlie autosomal recessive inheritance. Data on the frequency and distribution of mutations in large cohorts are currently limited. The purpose of this study was therefore to comprehensively examine the genetic architecture of AOS in an extensive cohort. Molecular diagnostic screening of 194 AOS/ACC/TTLD probands/families was conducted using next-generation and/or capillary sequencing analyses. In total, we identified 63 (likely) pathogenic mutations, comprising 56 distinct and 22 novel mutations, providing a molecular diagnosis in 30% of patients. Taken together with previous reports, these findings bring the total number of reported disease variants to 63, with a diagnostic yield of 36% in familial cases. NOTCH1 is the major contributor, underlying 10% of AOS/ACC/TTLD cases, with DLL4 (6%), DOCK6 (6%), ARHGAP31 (3%), EOGT (3%), and RBPJ (2%) representing additional causality in this cohort. We confirm the relevance of genetic screening across the AOS/ACC/TTLD spectrum, highlighting preliminary but important genotype-phenotype correlations. This cohort offers potential for further gene identification to address missing heritability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175364PMC
September 2018

Extending the clinical and genetic spectrum of ARID2 related intellectual disability. A case series of 7 patients.

Eur J Med Genet 2019 Jan 23;62(1):27-34. Epub 2018 Apr 23.

West of Scotland Regional Genetics Service, Laboratory Medicine Building, Queen Elizabeth University Hospital, Glasgow, United Kingdom. Electronic address:

In the last 3 years de novo sequence variants in the ARID2 (AT-rich interaction domain 2) gene, a subunit of the SWI/SNF complex, have been linked to intellectual disabilities in 3 case reports including one which describes frameshift mutations in ARID2 in 2 patients with features resembling Coffin-Siris syndrome. Coffin-Siris syndrome (CSS) is a rare congenital syndrome characterized by intellectual deficit, coarse facial features and hypoplastic or absent fifth fingernails and/or toenails among other features. Mutations in a number of different genes encoding SWI/SNF chromatin remodelling complex proteins have been described but the underlying molecular cause remains unknown in approximately 40% of patients with CSS. Here we describe 7 unrelated individuals, 2 with deletions of the ARID2 region and 5 with de novo truncating mutations in the ARID2 gene. Similarities to CSS are evident. Although hypertrichosis and hypoplasia of the fifth finger nail and distal phalanx do not appear to be common in these patients, toenail hypoplasia and the presence of Wormian bones might support the involvement of ARID2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmg.2018.04.014DOI Listing
January 2019

A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3.

Hum Mutat 2018 05 6;39(5):621-634. Epub 2018 Mar 6.

Department of Medical Genetics, Children's Hospital of Eastern Ontario, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.

The Loeys-Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor-β (TGF-β) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF-β signaling. More recently, TGF-β ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF-β pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF-β signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947146PMC
May 2018

Extreme phenotypes of Loeys Dietz syndrome.

Clin Dysmorphol 2017 Apr;26(2):91-94

aBristol Genetics Serivce bBristol Heart Institute, UHBristol NHS Foundation Trust, Bristol, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCD.0000000000000173DOI Listing
April 2017

Clinical utility gene card for: Cantú syndrome.

Eur J Hum Genet 2017 04 4;25(4). Epub 2017 Jan 4.

Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ejhg.2016.185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386410PMC
April 2017

Rare XXY/XX mosaicism in a phenotypic male presenting as cystic hygroma in the first trimester.

Clin Dysmorphol 2017 Apr;26(2):107-109

Departments of aClinical Genetics bPaediatric Endocrinology cFetal Medicine, University Hospitals Bristol NHS Trust dDepartment of Fetal Medicine eCytogenetics Department, Bristol Genetics Laboratory, Southmead Hospital, North Bristol NHS Trust, Bristol, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCD.0000000000000150DOI Listing
April 2017

A report of a new case of an interstitial deletion at 3p25.3 and expansion of the clinical phenotype.

Clin Dysmorphol 2014 Apr;23(2):63-66

Department of Clinical Genetics, St Michael's Hospital Department of Paediatric Ophthalmology, University Hospitals Bristol Centre for Child and Adolescent Health, School of Social and Community Medicine, University of Bristol, Bristol National Genetics Education and Development Centre, Birmingham Women's Hospital, Birmingham, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCD.0000000000000030DOI Listing
April 2014

Dominant missense mutations in ABCC9 cause Cantú syndrome.

Nat Genet 2012 May 18;44(7):793-6. Epub 2012 May 18.

Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.

Cantú syndrome is characterized by congenital hypertrichosis, distinctive facial features, osteochondrodysplasia and cardiac defects. By using family-based exome sequencing, we identified a de novo mutation in ABCC9. Subsequently, we discovered novel dominant missense mutations in ABCC9 in 14 of the 16 individuals with Cantú syndrome examined. The ABCC9 protein is part of an ATP-dependent potassium (K(ATP)) channel that couples the metabolic state of a cell with its electrical activity. All mutations altered amino acids in or close to the transmembrane domains of ABCC9. Using electrophysiological measurements, we show that mutations in ABCC9 reduce the ATP-mediated potassium channel inhibition, resulting in channel opening. Moreover, similarities between the phenotype of individuals with Cantú syndrome and side effects from the K(ATP) channel agonist minoxidil indicate that the mutations in ABCC9 result in channel opening. Given the availability of ABCC9 antagonists, our findings may have direct implications for the treatment of individuals with Cantú syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.2324DOI Listing
May 2012

Cantú syndrome: report of nine new cases and expansion of the clinical phenotype.

Am J Med Genet A 2011 Mar 22;155A(3):508-18. Epub 2011 Feb 22.

Department of Clinical Genetics, St. Michael's Hospital, Bristol, UK.

Cantú syndrome, a rare disorder of congenital hypertrichosis, characteristic facial anomalies, cardiomegaly, and osteochondrodysplasia was first described in 1982 by Cantú. Twenty-three cases of Cantú syndrome have been reported to date. The pathogenesis of this rare autosomal dominant condition is unknown. We describe 10 patients with Cantú syndrome (9 new cases and the long-term follow-up of a 10th case reported by Robertson in 1999) comparing the phenotype with that of the previously reported cases. We describe how the distinctive facial appearance evolves with time and report several new findings including recurrent infections with low immunoglobulin levels and gastric bleeding in some of our patients. The cardiac manifestations include patent ductus arteriosus, septal hypertrophy, pulmonary hypertension, and pericardial effusions. They may follow a benign course, but of the 10 cases we report, 4 patients required surgical closure of the patent ductus arteriosus and 1 patient a pericardectomy. Long-term follow-up of these patients has shown reassuring neuro-developmental outcome and the emergence of a behavior phenotype including obsessive traits and anxiety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.33885DOI Listing
March 2011
-->