PMID- 38112911
OWN - NLM
STAT- Publisher
LR  - 20231219
IS  - 1720-8386 (Electronic)
IS  - 0391-4097 (Linking)
DP  - 2023 Dec 19
TI  - MKRN3 circulating levels in girls with central precocious puberty caused by MKRN3 
      gene mutations.
LID - 10.1007/s40618-023-02255-5 [doi]
AB  - PURPOSE: MKNR3 is a paternally expressed gene whose mutations are the main cause 
      of central precocious puberty (CPP). Protein circulating levels can be easily 
      measured, as demonstrated in idiopathic CPP and healthy controls. No data are 
      available for patients harboring an MKRN3 mutation. Our aim was to perform MKRN3 
      mutation screening and to investigate if circulating protein levels could be a 
      screening tool to identify MKRN3 mutation in CPP patients. METHODS: We enrolled 
      140 CPP girls and performed MKRN3 mutation analysis. Patients were stratified 
      into two groups: idiopathic CPP (iCPP) and MKRN3 mutation-related CPP 
      (MKRN3-CPP). Clinical characteristics were collected. Serum MKRN3 values were 
      measured by a commercially available ELISA assay kit in MKRN3-CPP and a subgroup 
      of 15 iCPP patients. RESULTS: We identified 5 patients with MKRN3 mutations: one 
      was a novel mutation (p.Gln352Arg) while the others were previously reported 
      (p.Arg328Cys, p.Arg345Cys, p.Pro160Cysfs*14, p.Cys410Ter). There was a 
      significant difference in circulating MKRN3 values in MKRN3-CPP compared to iCPP 
      (p < 0.001). In MKRN3-CPP, the subject harboring Pro160Cysfs*14 presented 
      undetectable levels. Subjects carrying the missense mutations p.Arg328Cys and 
      p.Gln352Arg showed divergent circulating protein levels, respectively 40.56 pg/mL 
      and undetectable. The patient with the non-sense mutation reported low but 
      measurable MKRN3 levels (12.72 pg/mL). CONCLUSIONS: MKRN3 defect in patients with 
      CPP cannot be predicted by MKRN3 circulating levels, although those patients 
      presented lower protein levels than iCPP. Due to the great inter-individual 
      variability of the assay and the lack of reference values, no precise cut-off can 
      be identified to suspect MKRN3 defect.
CI  - (c) 2023. The Author(s), under exclusive licence to Italian Society of 
      Endocrinology (SIE).
FAU - Aiello, F
AU  - Aiello F
AUID- ORCID: 0000-0001-5912-3185
AD  - Department of Women's and Children's Health and General and Specialized Surgery, 
      University of Campania "Luigi Vanvitelli", Via Luigi De Crecchio 2, 80138, 
      Napoli, Italy.
FAU - Palumbo, S
AU  - Palumbo S
AUID- ORCID: 0000-0002-8084-9818
AD  - Department of Women's and Children's Health and General and Specialized Surgery, 
      University of Campania "Luigi Vanvitelli", Via Luigi De Crecchio 2, 80138, 
      Napoli, Italy. stefaniapalumbo4@gmail.com.
FAU - Cirillo, G
AU  - Cirillo G
AUID- ORCID: 0000-0002-7823-972X
AD  - Department of Women's and Children's Health and General and Specialized Surgery, 
      University of Campania "Luigi Vanvitelli", Via Luigi De Crecchio 2, 80138, 
      Napoli, Italy.
FAU - Tornese, G
AU  - Tornese G
AUID- ORCID: 0000-0002-4395-3915
AD  - Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.
FAU - Fava, D
AU  - Fava D
AUID- ORCID: 0000-0002-0128-6501
AD  - Pediatric Endocrinology Unit, Department of Pediatrics, IRCCS Istituto Giannina 
      Gaslini, 16147, Genoa, Italy.
AD  - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and 
      Child Health, University of Genoa, 16147, Genoa, Italy.
FAU - Wasniewska, M
AU  - Wasniewska M
AUID- ORCID: 0000-0002-8299-2677
AD  - Department of Human Pathology of Adulthood and Childhood, University of Messina, 
      Messina, Italy.
FAU - Faienza, M F
AU  - Faienza MF
AUID- ORCID: 0000-0002-1899-8337
AD  - Department of Precision and Regenerative Medicine and Ionian Area, University of 
      Bari "Aldo Moro", Bari, Italy.
AD  - Unit of Endocrinology and Rare Endocrine Diseases, Giovanni XXIII Pediatric 
      Hospital, Bari, Italy.
FAU - Bozzola, M
AU  - Bozzola M
AUID- ORCID: 0000-0002-4882-3714
AD  - Pediatric and Adolescent Unit, Department of Internal Medicine and Therapeutics, 
      University of Pavia, Pavia, Italy.
AD  - Onlus, Il Bambino e Il Suo Pediatra, Novara, Galliate, Italy.
FAU - Luongo, C
AU  - Luongo C
AD  - Department of Women's and Children's Health and General and Specialized Surgery, 
      University of Campania "Luigi Vanvitelli", Via Luigi De Crecchio 2, 80138, 
      Napoli, Italy.
FAU - Festa, A
AU  - Festa A
AUID- ORCID: 0000-0002-6747-445X
AD  - Department of Women's and Children's Health and General and Specialized Surgery, 
      University of Campania "Luigi Vanvitelli", Via Luigi De Crecchio 2, 80138, 
      Napoli, Italy.
FAU - Miraglia Del Giudice, E
AU  - Miraglia Del Giudice E
AUID- ORCID: 0000-0002-9410-5393
AD  - Department of Women's and Children's Health and General and Specialized Surgery, 
      University of Campania "Luigi Vanvitelli", Via Luigi De Crecchio 2, 80138, 
      Napoli, Italy.
FAU - Grandone, A
AU  - Grandone A
AUID- ORCID: 0000-0002-6343-4768
AD  - Department of Women's and Children's Health and General and Specialized Surgery, 
      University of Campania "Luigi Vanvitelli", Via Luigi De Crecchio 2, 80138, 
      Napoli, Italy.
LA  - eng
GR  - 390/Universita degli Studi della Campania Luigi Vanvitelli/
PT  - Journal Article
DEP - 20231219
PL  - Italy
TA  - J Endocrinol Invest
JT  - Journal of endocrinological investigation
JID - 7806594
SB  - IM
OTO - NOTNLM
OT  - Central precocious puberty
OT  - Children
OT  - MKRN3
OT  - Molecular screening
OT  - Mutation screening
OT  - Serum MKRN3
EDAT- 2023/12/19 19:53
MHDA- 2023/12/19 19:53
CRDT- 2023/12/19 11:21
PHST- 2023/07/21 00:00 [received]
PHST- 2023/11/21 00:00 [accepted]
PHST- 2023/12/19 19:53 [medline]
PHST- 2023/12/19 19:53 [pubmed]
PHST- 2023/12/19 11:21 [entrez]
AID - 10.1007/s40618-023-02255-5 [pii]
AID - 10.1007/s40618-023-02255-5 [doi]
PST - aheadofprint
SO  - J Endocrinol Invest. 2023 Dec 19. doi: 10.1007/s40618-023-02255-5.