Research Interests

My principal research interest lies in elucidating the genetic and environmental determinants of congenital hypothyroidism (CH), the commonest neonatal endocrine disorder, due either to failure of thyroid gland development (dysgenesis) or function (dyshormonogenesis). Central hypothyroidism, a rarer entity, is due to impaired thyrotropin (TSH) production by the pituitary gland.

I use candidate gene, gene panel and whole exome sequencing technologies to identify known and novel genetic causes of CH. I then undertake phenotyping of genetically ascertained individuals with parallel molecular and murine studies, aiming to gain new insights into thyroid biology and associated extra-thyroidal phenotypes.

Selected Publications

Zdraveska N, Kocova M, Nicholas AK, Anastasovska V, Schoenmakers N. Genetics of Gland-in-situ or Hypoplastic Congenital Hypothyroidism in Macedonia. Front Endocrinol (Lausanne). 2020 ;11:413. PMID: 32765423

Joustra SD, Roelfsema F, van Trotsenburg ASP, Schneider HJ, Kosilek RP, Kroon HM, Logan JG, Butterfield NC, Zhou X, Toufaily C, Bak B, Turgeon MO, Brûlé E, Steyn FJ, Gurnell M, Koulouri O, Le Tissier P, Fontanaud P, Duncan Bassett JH, Williams GR, Oostdijk W, Wit JM, Pereira AM, Biermasz NR, Bernard DJ, Schoenmakers N. IGSF1 Deficiency Results in Human and Murine Somatotrope Neurosecretory Hyperfunction. J Clin Endocrinol Metab. 2020;105(3):e70-84. PMID: 31650157

Peters C, Nicholas AK, Schoenmakers E, Lyons G, Langham S, Serra EG, Sebire NJ, Muzza M, Fugazzola L, Schoenmakers N. DUOX2/DUOXA2 Mutations Frequently Cause Congenital  Hypothyroidism that Evades Detection on Newborn Screening in the United Kingdom. Thyroid. 2019 Jun;29(6):790-801. PMID: 31044655

Cangul H*, Liao XH*, Schoenmakers E, Kero J, Barone S, Srichomkwun P, Iwayama H, Serra EG, Saglam H, Eren E, Tarim O, Nicholas AK, Zvetkova I, Anderson CA, Frankl FEK, Boelaert K, Ojaniemi M, Jääskeläinen J, Patyra K, Löf C, Williams ED; UK10K Consortium, Soleimani M, Barrett T, Maher ER, Chatterjee VK, Refetoff S**, Schoenmakers N**. Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism. JCI Insight. 2018 Oct 18;3(20). pii: 99631. PMID: 30333321

Aycan Z, Cangul H, Muzza M, Bas VN, Fugazzola L, Chatterjee VK, Persani L, Schoenmakers N. Digenic DUOX1 and DUOX2 Mutations in Cases With Congenital Hypothyroidism. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3085-3090. PMID: 28633507

Boudellioua I, Mahamad Razali RB, Kulmanov M, Hashish Y, Bajic VB, Goncalves-Serra E, Schoenmakers N, Gkoutos GV, Schofield PN, Hoehndorf R. Semantic prioritization of novel causative genomic variants. PLoS Comput Biol. 2017 Apr 17;13(4):e1005500. PMID: 28414800

Nicholas AK, Serra EG, Cangul H, Alyaarubi S, Ullah I, Schoenmakers E, Deeb A, Habeb AM, AlMaghamsi M, Peters C, Nathwani N, Aycan Z, Saglam H, Bober E, Dattani M, Shenoy S, Murray PG, Babiker A, Willemsen R, Thankamony A, Lyons G, Irwin R, Padidela R, Tharian K, Davies JH, Puthi V, Park SM, Massoud AF, Gregory JW, Albanese A, Pease-Gevers E, Martin H, Brugger K, Maher ER, Chatterjee K, Anderson CA, Schoenmakers N. 2016 Comprehensive screening of eight known causative genes in congenital hypothyroidism with gland-in-situ (2016) J Clin Endocrinol Metab. 2016 Aug 15:jc20161879 PMID: 27525530

Joustra SD, Heinen CA, Schoenmakers N, Bonomi M, Ballieux BE, Turgeon MO, Bernard DJ, Fliers E, van Trotsenburg AS, Losekoot M, Persani L, Wit JM, Biermasz NR, Pereira AM, Oostdijk W; IGSF1 Clinical Care Group. 2016 IGSF1 Deficiency: Lessons from an extensive case series and recommendations for Clinical Management  (2016) J Clin Endocrinol Metab. 101(4):1627-36. PMID: 26840047

Koulouri O, Nicholas AK, Schoenmakers E, Mokrosinski J, Lane F, Cole T, Kirk J, Farooqi IS, Chatterjee VK, Gurnell M, Schoenmakers N. 2016 A Novel Thyrotropin-Releasing Hormone Missense Mutation (P81R) in Central Congenital Hypothyroidism (2016) J Clin Endocrinol Metab. 101(3):847-51. PMID: 26735259

Schoenmakers N*, Moran C*, Campi I, Agostini M, Bacon O, Rajanayagam O, Schwabe J, Bradbury S, Barrett T, Geohegan F, Druce M, Beck-Peccoz P, O’Toole A, Clark P, Bignell M, Lyons G, Halsall D, Gurnell M, Chatterjee K. (2014) A novel albumin gene mutation (R222I) in Familial Dysalbuminaemic Hyperthyroxinaemia. J Clin Endocrinol Metab. 99(7):E1381-6. PMID: 24646103

Moran C*, Schoenmakers N*, Agostini M, Schoenmakers E, Offiah A, Kydd A, Kahaly G, Mohr-Kahaly S, Rajanayagam O, Lyons G, Wareham N, Halsall D, Dattani M, Hughes S, Gurnell M, Park S-M, Chatterjee VKK. An adult female with Resistance to Thyroid Hormone mediated by defective thyroid hormone receptor alpha. (2013) J. Clin. Endocrinol. Metab. 98: 4254-4261. PMID: 23940126

Joustra SD, Schoenmakers N, Persani L, Campi I, Bonomi M, Radetti G, Beck-Peccoz P, Zhu H, Davis TME, Sun Y, Corssmit EP, Appelman-Dijkstra NM, Heinen CA, Pereira AM, Varewijck AJ, Janssen JAMJL, Endert E, Hennekam RC, Lombardi MP, Mannens MMAM, Bak B, Bernard DJ, Breuning MH, Chatterjee K, Dattani MT, Oostdijk W, Biermasz NR, Wit JM, van Trotsenburg ASP. The IGSF-1 deficiency syndrome: characteristics of male and female patients. J. Clin. Endocrinol. Metab. 2013; 98: 4942-4952. PMID: 24108313

Bochukova E*, Schoenmakers N*, Agostini M, Schoenmakers E, Rajanayagam O, Keogh JM, Henning E, Reinemund J, Gevers E, Sarri M, Downes K, Offiah A, Albanese A, Halsall D, Schwabe J, Bain M, Lindley K, Muntoni F, Vargha Khadem F, Dattani M, Farooqi S, Gurnell M, Chatterjee K. (2012). A Dominant Negative Mutation in the Thyroid Hormone Receptor Alpha Gene. New England Journal of Medicine, 366:243-249. PMID: 22168587. (* coequal first authors)

Sun Y*, Bak B*, Schoenmakers N*, van Trostsenburg ASP*, Oostdijk W, Voshol P, Cambridge E, White JK, le Tissier P, Gharavy SNM, Martinez-Barbera JP, Stokvis-Brantsma WH, Vulsma T, Kempers MJ, Persani L, Campi I, Bonomi M, Beck-Peccoz P, Zhu H, Davis TME, Hokken-Koelega ACS, Del Blanco DG, Rangasami JJ, Ruivenkamp CAL, Laros JFJ, Kriek M, Kant SG, Bosch CAJ, Biermasz NR, Appelman-Dijkstra NM, Corssmit EP, Hovens GCJ, Pereira AM, den Dunnen JT, Wade MR, Breuning MH, Hennekam RC, Chatterjee K†, Dattani MT†, Wit JM†, Bernard DJ†. (2012). Loss-of-function mutations in IGSF1 cause a X-linked syndrome of central hypothyroidism and testicular enlargement. Nature Genetics, 44, 1375-1381 (*coequal first authors). PMID: 23143598.

 

(* = joint first authors)