The role of next generation sequencing in understanding male and female sexual development: clinical implications

References

• Narasimhan VM, Xue Y, Tyler-Smith C. Human knockout carriers: dead, diseased, healthy, or improved? Trends Mol Med. 2016;22(4):341–351.
   PubMed Web of Science ®Google Scholar
• 1000 Genomes Project Consortium, Abecasis GR, Altshuler D, et al. A map of human genome variation from population-scale sequencing. Nature. 2010;467(7319):1061–1073.
   PubMed Web of Science ®Google Scholar
• 1000 Genomes Project Consortium, Auton A, Brooks LD, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68–74.
   PubMed Web of Science ®Google Scholar
• MacArthur DG, Balasubramanian S, Frankish A, et al. A systematic survey of loss-of-function variants in human protein-coding genes. Science. 2012;335(6070):823–828.
   PubMed Web of Science ®Google Scholar
• Piton A, Redin C, Mandel JL. XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing. Am J Hum Genet. 2013;93(2):368–383.
   PubMed Web of Science ®Google Scholar
• Cassa CA, Tong MY, Jordan DM. Large numbers of genetic variants considered to be pathogenic are common in asymptomatic individuals. Hum Mutat. 2013;34(9):1216–1220.
   PubMed Web of Science ®Google Scholar
• Lam HY, Clark MJ, Chen R, et al. Performance comparison of whole-genome sequencing platforms. Nat Biotechnol. 2011;30:78–82.
   PubMed Web of Science ®Google Scholar
• Meienberg J, Bruggmann R, Oexle K, et al. Clinical sequencing: is WGS the better WES? Hum Genet. 2016;135(3):359–362.
   PubMed Web of Science ®Google Scholar
• Patwardhan A, Harris J, Leng N, et al. Achieving high-sensitivity for clinical applications using augmented exome sequencing. Genome Med. 2015;7(1):71.
   PubMed Web of Science ®Google Scholar
• Meynert AM, Ansari M, FitzPatrick DR, et al. Variant detection sensitivity and biases in whole genome and exome sequencing. BMC Bioinformatics. 2014;15:247.
   PubMed Web of Science ®Google Scholar
• Dewey FE, Grove ME, Pan C, et al. Clinical interpretation and implications of whole-genome sequencing. JAMA. 2014;311(10):1035–1045.
   PubMed Web of Science ®Google Scholar
• O’Rawe J, Jiang T, Sun G, et al. Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing. Genome Med. 2013;5(3):28.
   PubMed Web of Science ®Google Scholar
• Fang H, Wu Y, Narzisi G, et al. Reducing INDEL calling errors in whole genome and exome sequencing data. Genome Med. 2014;6(10):89.
   PubMed Web of Science ®Google Scholar
• Goldfeder RL, Priest JR, Zook JM, et al. Medical implications of technical accuracy in genome sequencing. Genome Med. 2016;8(1):24.
   PubMed Web of Science ®Google Scholar
• Krøigård AB, Thomassen M, Lænkholm AV, et al. Evaluation of nine somatic variant callers for detection of somatic mutations in exome and targeted deep sequencing data. PLoS One. 2016;11(3):e0151664.
   Web of Science ®Google Scholar
• Challis D, Antunes L, Garrison E, et al. The distribution and mutagenesis of short coding INDELs from 1,128 whole exomes. BMC Genomics. 2015;16:143.
   PubMed Web of Science ®Google Scholar
• Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4(7):1073–1081.
   PubMed Web of Science ®Google Scholar
• Reva B, Antipin Y, Sander C. Predicting the functional impact of protein mutations: application to cancer genomics. Nucleic Acids Res. 2011;39(17):e118.
   PubMed Web of Science ®Google Scholar
• Stone EA. Sidow A physicochemical constraint violation by missense substitutions mediates impairment of protein function and disease severity. Genome Res. 2005;15(7):978–986.
   PubMed Web of Science ®Google Scholar
• Mathe E, Olivier M, Kato S, et al. Computational approaches for predicting the biological effect of p53 missense mutations: a comparison of three sequence analysis based methods. Nucleic Acids Res. 2006;34(5):1317–1325.
   PubMed Web of Science ®Google Scholar
• Thomas PD, Kejariwal A. Coding single-nucleotide polymorphisms associated with complex vs. Mendelian disease: evolutionary evidence for differences in molecular effects. Proc Natl Acad Sci USA. 2004;101(43):15398–15403.
   PubMed Web of Science ®Google Scholar
• Cooper GM, Stone EA, Asimenos G, et al. Distribution and intensity of constraint in mammalian genomic sequence. Genome Res. 2005;15(7):901–913.
   PubMed Web of Science ®Google Scholar
• Adzhubei IA, Schmidt S, Peshkin L, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7(4):248–249.
   PubMed Web of Science ®Google Scholar
• Kircher M, Witten DM, Jain P, et al. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014;46(3):310–315.
   PubMed Web of Science ®Google Scholar
• van der Velde KJ, Kuiper J, Thompson BA, et al. InSiGHT group. Evaluation of CADD scores in curated mismatch repair gene variants yields a model for clinical validation and prioritization. Hum Mutat. 2015;36(7):712–719.
   PubMed Web of Science ®Google Scholar
• Mangold E, Böhmer AC, Ishorst N, et al. Sequencing the GRHL3 coding region reveals rare truncating mutations and a common susceptibility variant for nonsyndromic cleft palate. Am J Hum Genet. 2016;98(4):755–762.
   PubMed Web of Science ®Google Scholar
• Dong C, Wei P, Jian X, et al. Comparison and integration of deleteriousness prediction methods for nonsynonymous SNVs in whole exome sequencing studies. Hum Mol Genet. 2015;24(8):2125–2137.
   PubMed Web of Science ®Google Scholar
• Stenson PD, Mort M, Ball EV, et al. The human gene mutation database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum Genet. 2014;133(1):1–9.
   PubMed Web of Science ®Google Scholar
• Stanley CM, Sunyaev SR, Greenblatt MS, et al. Clinically relevant variants - identifying, collecting, interpreting, and disseminating: the 2013 annual scientific meeting of the human genome variation society. Hum Mutat. 2014;35(4):505–510.
   PubMed Web of Science ®Google Scholar
• Petrovski S, Wang Q, Heinzen EL, et al. Genic intolerance to functional variation and the interpretation of personal genomes. PLoS Genet. 2013;9(8):e1003709.
   PubMed Web of Science ®Google Scholar
• Gussow AB, Petrovski S, Wang Q, et al. The intolerance to functional genetic variation of protein domains predicts the localization of pathogenic mutations within genes. Genome Biol. 2016;17(1):9.
   PubMed Web of Science ®Google Scholar
• Samocha KE, Robinson EB, Sanders SJ, et al. A framework for the interpretation of de novo mutation in human disease. Nat Genet. 2014;46(9):944–950.
   PubMed Web of Science ®Google Scholar
• Itan Y, Shang L, Boisson B, et al. The human gene damage index as a gene-level approach to prioritizing exome variants. Proc Natl Acad Sci U S A. 2015;112(44):13615–13620.
   PubMed Web of Science ®Google Scholar
• Itan Y, Shang L, Boisson B, et al. The mutation significance cutoff: gene-level thresholds for variant predictions. Nat Methods. 2016;13(2):109–110.
   PubMed Web of Science ®Google Scholar
• Goldstein DB, Allen A, Keebler J, et al. Sequencing studies in human genetics: design and interpretation. Nat Rev Genet. 2013;14(7):460–470.
   PubMed Web of Science ®Google Scholar
• MacArthur DG, Manolio TA, Dimmock DP, et al. Guidelines for investigating causality of sequence variants in human disease. Nature. 2014;508(7497):469–476.
   PubMed Web of Science ®Google Scholar
• Chong JX, Buckingham KJ, Jhangiani SN, et al. The genetic basis of mendelian phenotypes: discoveries, challenges, and opportunities. Am J Hum Genet. 2015;97(2):199–215.
   PubMed Web of Science ®Google Scholar
• Brookes AJ, Robinson PN. Human genotype-phenotype databases: aims, challenges and opportunities. Nat Rev Genet. 2015 Dec;16(12):702–715.
   PubMed Web of Science ®Google Scholar
• Bashamboo A, McElreavey K. Human sex-determination and disorders of sex-development (DSD). Semin Cell Dev Biol. 2015;45:77–83.
   PubMed Web of Science ®Google Scholar
• Bashamboo A, Ferraz-de-Souza B, Lourenço D, et al. Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1. Am J Hum Genet. 2010;87(4):505–512.
   PubMed Web of Science ®Google Scholar
• Philibert P, Zenaty D, Lin L, et al. Mutational analysis of steroidogenic factor 1 (NR5a1) in 24 boys with bilateral anorchia: a French collaborative study. Hum Reprod. 2007;22(12):3255–3261.
   PubMed Web of Science ®Google Scholar
• Achermann JC, Ito M, Ito M, et al. A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. Nat Genet. 1999;22(2):125–126.
   PubMed Web of Science ®Google Scholar
• Allali S, Muller JB, Brauner R, et al. Mutation analysis of NR5A1 encoding steroidogenic factor 1 in 77 patients with 46, XY disorders of sex development (DSD) including hypospadias. PLoS One. 2011;6(10):e24117.
   PubMed Web of Science ®Google Scholar
• Lourenço D, Brauner R, Lin L, et al. Mutations in NR5A1 associated with ovarian insufficiency. N Engl J Med. 2009;360(12):1200–1210.
   PubMed Web of Science ®Google Scholar
• Biason-Lauber A, Schoenle EJ. Apparently normal ovarian differentiation in a prepubertal girl with transcriptionally inactive steroidogenic factor 1 (NR5A1/SF-1) and adrenocortical insufficiency. Am J Hum Genet. 2000;67(6):1563–1568.
   PubMed Web of Science ®Google Scholar
• Zangen D, Kaufman Y, Banne E, et al. Testicular differentiation factor SF-1 is required for human spleen development. J Clin Invest. 2014;124(5):2071–2075.
   PubMed Web of Science ®Google Scholar
• Suwanai AS, Ishii T, Haruna H, et al. A report of two novel NR5A1 mutation families: possible clinical phenotype of psychiatric symptoms of anxiety and/or depression. Clin Endocrinol (Oxf). 2013;78(6):957–965.
   PubMed Web of Science ®Google Scholar
• Mazen I, Abdel-Hamid M, Mekkawi M, et al. Identification of NR5A1 mutations and possible digenic inheritance in 46,XY gonadal dysgenesis. Sex Dev. In press.
   Google Scholar
• Green RC, Berg JS, Grody WW, et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013;15(7):565–574.
   PubMed Web of Science ®Google Scholar
• ACMG Board of Directors. ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing. Genet Med. 2015;17(1):68–69.
   PubMedGoogle Scholar
• Burke W, Antommaria AH, Bennett R, et al. Recommendations for returning genomic incidental findings? We need to talk!. Genet Med. 2013;15:854–859.
   PubMed Web of Science ®Google Scholar
• Holtzman NA. ACMG recommendations on incidental findings are flawed scientifically and ethically. Genet Med. 2013;15:750–751.
   PubMed Web of Science ®Google Scholar
• Townsend A, Adam S, Birch PH, et al. Paternalism and the ACMG recommendations on genomic incidental findings: patients seen but not heard. Genet Med. 2013;15:751–752.
   PubMed Web of Science ®Google Scholar
• Schuol S, Schickhardt C, Wiemann S, et al. So rare we need to hunt for them: reframing the ethical debate on incidental findings. Genome Med. 2015;7(1):83.
   PubMed Web of Science ®Google Scholar
• Hegde M, Bale S, Bayrak-Toydemir P, et al. Reporting incidental findings in genomic scale clinical sequencing–a clinical laboratory perspective: a report of the association for molecular pathology. J Mol Diagn. 2015;17(2):107–117.
   PubMed Web of Science ®Google Scholar
• Hehir-Kwa JY, Claustres M, Hastings RJ, et al. Towards a European consensus for reporting incidental findings during clinical NGS testing. Eur J Hum Genet. 2015;23(12):1601–1606.
   PubMed Web of Science ®Google Scholar
• Knoppers BM, Zawati MH, Sénécal K. Return of genetic testing results in the era of whole-genome sequencing. Nat Rev Genet. 2015;16(9):553–559.
   PubMed Web of Science ®Google Scholar
• Hunter JE, Irving SA, Biesecker LG, et al. A standardized, evidence-based protocol to assess clinical actionability of genetic disorders associated with genomic variation. Genet Med. 2016 Apr 28.
   PubMedGoogle Scholar
• Lawrence L, Sincan M, Markello T, et al. The implications of familial incidental findings from exome sequencing: the NIH undiagnosed diseases program experience. Genet Med. 2014;16(10):741–750.
   PubMed Web of Science ®Google Scholar
• Rehm HL, Bale SJ, Bayrak-Toydemir P, et al. Working group of the American college of medical genetics and genomics laboratory quality assurance commitee. ACMG clinical laboratory standards for next-generation sequencing. Genet Med. 2013;15(9):733–747.
   PubMed Web of Science ®Google Scholar
• Amendola LM, Dorschner MO, Robertson PD, et al. Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 2015;25(3):305–315.
   PubMed Web of Science ®Google Scholar
• Gargis AS, Kalman L, Bick DP, et al. Good laboratory practice for clinical next-generation sequencing informatics pipelines. Nat Biotechnol. 2015;33(7):689–693.
   PubMed Web of Science ®Google Scholar
• Dewey FE, Grove ME, Priest JR, et al. Sequence to medical phenotypes: a framework for interpretation of human whole genome DNA sequence data. PLoS Genet. 2015;11(10):e1005496.
   PubMed Web of Science ®Google Scholar
• Philippakis AA, Azzariti DR, Beltran S, et al. The matchmaker exchange: a platform for rare disease gene discovery. Hum Mutat. 2015;36(10):915–921.
   PubMed Web of Science ®Google Scholar
• Krawitz P, Buske O, Zhu N, et al. The genomic birthday paradox: how much is enough? Hum Mutat. 2015;36(10):989–997.
   PubMed Web of Science ®Google Scholar
• Lourenço D, Brauner R, Rybczynska M, et al. Loss-of-function mutation in GATA4 causes anomalies of human testicular development. Proc Natl Acad Sci U S A. 2011;108(4):1597–1602.
   PubMed Web of Science ®Google Scholar
• White S, Ohnesorg T, Notini A, et al. Copy number variation in patients with disorders of sex development due to 46,XY gonadal dysgenesis. PLoS One. 2011;6(3):e17793.
   PubMed Web of Science ®Google Scholar
• Murphy MW, Lee JK, Rojo S, et al. An ancient protein-DNA interaction underlying metazoan sex determination. Nat Struct Mol Biol. 2015;22(6):442–451.
   PubMed Web of Science ®Google Scholar
• Thyen U, Lanz K, Holterhus PM, et al. Epidemiology and initial management of ambiguous genitalia at birth in Germany. Horm Res. 2006;66(4):195–203.
   PubMedGoogle Scholar
• Ahmed SF, Bashamboo A, Lucas-Herald A, et al. Understanding the genetic aetiology in patients with XY DSD. Br Med Bull. 2013;106:67–89.
   PubMed Web of Science ®Google Scholar
• Yang Y, Muzny DM, Xia F, et al. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA. 2014;312(18):1870–1879.
   PubMed Web of Science ®Google Scholar
• Mazen I, Amin H, Kamel A, et al. Homozygous mutation of the FGFR1 gene associated with congenital heart disease and 46,XY disorder of sex development. Sex Dev. 2016 Apr 8;10:16–22. [Epub ahead of print] PubMed PMID: 27055092.
   PubMed Web of Science ®Google Scholar
• Ben Hadj Hmida I, Mougou-Zerelli S, Hadded A, et al. Novel homozygous nonsense mutations in the luteinizing hormone receptor (LHCGR) gene associated with 46,XY primary amenorrhea. Fertil Steril. 2016;106:225–229.e11.
   Google Scholar
• Sirisena ND, McElreavey K, Bashamboo A, et al. A child with a novel de novo mutation in the aristaless domain of the aristaless-related homeobox (ARX) gene presenting with ambiguous genitalia and psychomotor delay. Sex Dev. 2014;8(4):156–159.
   PubMed Web of Science ®Google Scholar
• Werner R, Merz H, Birnbaum W, et al. 46,XY gonadal dysgenesis due to a homozygousmutation in desert hedgehog (DHH) identified by exome sequencing. J Clin Endocrinol Metab. 2015 Jul;100(7):E1022–E1029.
   PubMed Web of Science ®Google Scholar
• Kosfeld A, Kreuzer M, Daniel C, et al. Whole-exome sequencing identifies mutations of TBC1D1 encoding a Rab-GTPase-activating protein in patients with congenital anomalies of the kidneys and urinary tract (CAKUT). Hum Genet. 2016;135(1):69–87.
   PubMed Web of Science ®Google Scholar
• Vivante A, Kleppa MJ, Schulz J, et al. Mutations in TBX18 cause dominant urinary tract malformations via transcriptional dysregulation of ureter development. Am J Hum Genet. 2015;97(2):291–301.
   PubMed Web of Science ®Google Scholar
• Weinberg-Shukron A, Renbaum P, Kalifa R, et al. A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis. J Clin Invest. 2015;125(11):4295–4304.
   PubMed Web of Science ®Google Scholar
• Pierce SB, Walsh T, Chisholm KM, et al. Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault syndrome. Am J Hum Genet. 2010;87(2):282–288.
   PubMed Web of Science ®Google Scholar
• Callier P, Calvel P, Matevossian A, et al. Loss of function mutation in the palmitoyl-transferase HHAT leads to syndromic 46,XY disorder of sex development by impeding Hedgehog protein palmitoylation and signaling. PLoS Genet. 2014 May 1;10(5):e1004340.
   PubMed Web of Science ®Google Scholar
• Agha Z, Iqbal Z, Azam M, et al. Exome sequencing identifies three novel candidate genes implicated in intellectual disability. PLoS One. 2014;9(11):e112687.
   PubMed Web of Science ®Google Scholar
• Mroske C, Rasmussen K, Shinde DN, et al. Germline activating MTOR mutation arising through gonadal mosaicism in two brothers with megalencephaly and neurodevelopmental abnormalities. BMC Med Genet. 2015;16:102.
   PubMed Web of Science ®Google Scholar
• White J, Mazzeu JF, Hoischen A, et al. DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome. Am J Hum Genet. 2015;96(4):612–622.
   PubMed Web of Science ®Google Scholar
• Bashamboo A, Brauner R, Bignon-Topalovic J, et al. Mutations in the FOG2/ZFPM2 gene are associated with anomalies of human testis determination. Hum Mol Genet. 2014;23(14):3657–3665.
   PubMed Web of Science ®Google Scholar
• Baxter RM, Arboleda VA, Lee H, et al. Exome sequencing for the diagnosis of 46,XY disorders of sex development. J Clin Endocrinol Metab. 2015;100(2):E333–E344.
   PubMed Web of Science ®Google Scholar