Clinical presentation and molecular characterization of a novel patient with variant POC1A-related syndrome.
Acanthosis Nigricans
/ genetics
Adult
Age of Onset
Cell Cycle Proteins
/ deficiency
Computer Simulation
Congenital Hyperinsulinism
/ drug therapy
Cytoskeletal Proteins
/ deficiency
DNA, Complementary
/ genetics
Dyslipidemias
/ drug therapy
Exons
/ genetics
Fatty Acids, Unsaturated
/ therapeutic use
Female
Frameshift Mutation
Heterozygote
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ therapeutic use
Insulin Resistance
Metformin
/ therapeutic use
Middle Aged
Pedigree
Phenotype
Plasmapheresis
Protein Isoforms
/ genetics
Syndrome
Transcription, Genetic
POC1A
SOFT syndrome
centriolar function
dyslipidemia
insulin resistance
variant POC1A-related syndrome
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
18
04
2020
revised:
10
12
2020
accepted:
24
12
2020
pubmed:
30
12
2020
medline:
21
1
2022
entrez:
29
12
2020
Statut:
ppublish
Résumé
Biallelic pathogenic variants in POC1A result in SOFT (Short-stature, Onychodysplasia, Facial-dysmorphism, and hypoTrichosis) and variant POC1A-related (vPOC1A) syndromes. The latter, nowadays described in only two unrelated subjects, is associated with a restricted spectrum of variants falling in exon 10, which is naturally skipped in a specific POC1A mRNA. The synthesis of an amount of a POC1A isoform from this transcript in individuals with vPOC1A syndrome has been believed as the likely explanation for such a genotype-phenotype correlation. Here, we illustrate the clinical and molecular findings in a woman who resulted to be compound heterozygous for a recurrent frameshift variant in exon 10 and a novel variant in exon 9 of POC1A. Phenotypic characteristics of this woman included severe hyperinsulinemic dyslipidemia, acanthosis nigricans, moderate growth restriction, and dysmorphisms. These manifestations overlap the clinical features of the two previously published individuals with vPOC1A syndrome. RT-PCR analysis on peripheral blood and subsequent sequencing of the obtained amplicons demonstrated a variety of POC1A alternative transcripts that resulted to be expressed in the proband, in the healthy mother, and in controls. We illustrate the possible consequences of the two POC1A identified variants in an attempt to explain pleiotropy in vPOC1A syndrome.
Substances chimiques
Cell Cycle Proteins
0
Cytoskeletal Proteins
0
DNA, Complementary
0
Fatty Acids, Unsaturated
0
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
POC1A protein, human
0
Protein Isoforms
0
Metformin
9100L32L2N
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
540-546Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Li S, Fernandez JJ, Marshall WF, Agard DA. Electron cryo-tomography provides insight into procentriole architecture and assembly mechanism. Elife. 2019;8:e43434.
Venoux M, Tait X, Hames RS, Straatman KR, Woodland HR, Fry AM. Poc1A and Poc1B act together in human cells to ensure centriole integrity. J Cell Sci. 2013;126:163-175.
Keller LC, Geimer S, Romijn E, Yates J 3rd, Zamora I, Marshall WF. Molecular architecture of the centriole proteome: the conserved WD40 domain protein POC1 is required for centriole duplication and length control. MolBiol Cell. 2009;20:1150-1166.
Sarig O, Nahum S, Rapaport D, et al. Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis syndrome is caused by a POC1A mutation. Am J Hum Genet. 2012;91:337-342.
Shaheen R, Faqeih E, Shamseldin HE, et al. POC1A truncation mutation causes a ciliopathy in humans characterized by primordial dwarfism. Am J Hum Genet. 2012;91:330-336.
Koparir A, Karatas OF, Yuceturk B, et al. Novel POC1A mutation in primordial dwarfism reveals new insights for centriole biogenesis. Hum Mol Genet. 2015;24:5378-5387.
Barraza-Garcia J. Ivan Rivera-Pedroza C, Salamanca L, et al. two novel POC1A mutations in the primordial dwarfism, SOFT syndrome: clinical homogeneity but also unreported malformations. Am J Med Genet A. 2016;170A:210-216.
Ko JM, Jung S, Seo J, Shin CH, et al. SOFT syndrome caused by compound heterozygous mutations of POC1A and its skeletal manifestation. J Hum Genet. 2016;61:561-564.
Mostofizadeh N, Gheidarloo M, Hashemipour M, Dehkordi EH. SOFT syndrome: the first case in Iran. Adv Biomed Res. 2018;7:128.
Saida K, Silva S, Solar B, et al. SOFT syndrome in a patient from Chile. Am J Med Genet A. 2019;179:338-340.
Homma TK, Freire BL, HonjoKawahira RS, et al. Genetic disorders in prenatal onset syndromic short stature identified by exome sequencing. J Pediatr. 2019;215:192-198.
Al-Kindi A, Al-Shehhi M, Westenberger A, et al. A novel POC1A variant in an alternatively spliced exon causes classic SOFT syndrome: clinical presentation of seven patients. J Hum Genet. 2020;65:193-197.
Chen JH, Segni M, Payne F, et al. Truncation of POC1A associated with short stature and extreme insulin resistance. J Mol Endocrinol. 2015;55:147-158.
Giorgio E, Rubino E, Bruselles A, et al. A syndromic extreme insulin resistance caused by biallelic POC1A mutations in exon 10. Eur J Endocrinol. 2017;177:K21-K27.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405-424.
Weghofer A, Kim A, Barad DH, Gleicher N. Age at menarche: a predictor of diminished ovarian function? Fertil Steril. 2013;100:1039-1043.
Ding HR, Wang JL, Ren HZ, Lipometabolism SXL. Glycometabolism in liver diseases. Biomed Res Int. 2018;2018:1287127.
El-Kabbany ZA, Hamza RT, Ibrahim SA, Mahmoud NH. Dyslipidemia and hyperinsulinemia in children and adolescents with chronic liver disease: relation to disease severity. Int J Adolesc Med Health. 2014;26:195-201.
Lindeboom RG, Supek F, Lehner B. The rules and impact of nonsense-mediated mRNA decay in human cancers. Nat Genet. 2016;48:1112-1118.
Jain BP, Pandey S. WD40 repeat proteins: Signalling scaffold with diverse functions. Protein J. 2018;37:391-406.
Yee CS, Massaad MJ, Bainter W, et al. Recurrent viral infections associated with a homozygous CORO1A mutation that disrupts oligomerization and cytoskeletal association. J Allergy Clin Immunol. 2016 Mar;137(3):879-888.e2.
Drutman SB, Haerynck F, Zhong FL, et al. Homozygous NLRP1 gain-of-function mutation in siblings with a syndromic form of recurrent respiratory papillomatosis. Proc Natl Acad Sci U S A. 2019;116:19055-19063.
Cavaco BM, Canaff L, Nolin-Lapalme A, et al. Homozygous calcium-sensing receptor polymorphism R544Q presents as Hypocalcemic hypoparathyroidism. J Clin Endocrinol Metab. 2018;10:2879-2888.