PIEZO2  gene and its role in the development of distal arthrogryposis: A literature review

Varvara V. Chernyavskaya-Haukka; Чернявская-Хаукка Варвара Викторовна; Varvara V. Chernyavskaya-Haukka; Olga E. Agranovich; Агранович Ольга Евгеньевна; Olga E. Agranovich

doi:10.17816/PTORS121809

PIEZO2 gene and its role in the development of distal arthrogryposis: A literature review

Authors: Chernyavskaya-Haukka V.V.¹, Agranovich O.E.¹
Affiliations:
1. H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery
Issue: Vol 11, No 2 (2023)
Pages: 227-238
Section: Scientific reviews
URL: https://journals.eco-vector.com/turner/article/view/121809
DOI: https://doi.org/10.17816/PTORS121809
ID: 121809

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Abstract

BACKGROUND: PIEZO1 and PIEZO2 are mechanosensitive ion channel proteins; in humans, they are encoded by genes with identical names. PIEZO proteins convert mechanical signals into biochemical cellular responses following transduction. Recent data highlight the importance of this family of ion channel proteins in the regulation of physiological processes; however, many mechanisms remain unknown. Modern studies have proven that PIEZO2 mutations lead to the development of various forms of distal arthrogryposis.

AIM: To analyze publications containing information on PIEZO2 gene and its role in the development of distal forms of arthrogryposis.

MATERIALS AND METHODS: This study analyzed the results of a literature search in the open scientific literature databases of PubMed, Cochrane Library, and eLibrary. Consequently, 40 foreign, and domestic scientific sources were extracted from 1969 to 2022.

RESULTS: This study showed the relationship between PIEZO2 mutations and the development of the distal forms of arthrogryposis. The study also presented the types of distal arthrogryposis and their clinical manifestations depending on the mutation of this gene. PIEZO2 mutations with decreased function cause distal arthrogryposis with impaired proprioception and taction (autosomal recessive type of inheritance). PIEZO2 mutations with gain-of-function cause distal arthrogryposis of types 3 and 5 (autosomal dominant inheritance).

CONCLUSIONS: An integrated approach to the diagnosis and molecular genetic study will allow us to choose the best techniques and treatment of patients with this pathology. The results are useful for doctors of various specialties.

Keywords

distal arthrogryposis, PIEZO2 gene, mutations

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BACKGROUND

Throughout life, a person encounters various mechanical forces. This process is called mechanosensing, which includes the conscious perception of tactile sense (somatosensory), control of posture (proprioception), and unconscious regulation of physiological functions such as breathing and heart rate (interoception). In each case, mechanical force activates special cells called mechanoreceptors that generate and transmit signals to the nervous system and body. The key stage in mechanosensing is the conformation of molecules expressed in mechanoreceptors, which results in the conversion of mechanical forces into electrochemical signals (the so-called mechanotransduction). Tactile sense, as one of the variants of mechanical sensations, is an integral part of daily living. This sensory system is extremely sensitive, remarkably accurate, and fast, allowing the localization of the smallest forces, such as the movement of a single hair strand, in a fraction of a second [1]. Unraveling the mechanisms by which the sensory system achieves these results has been a major challenge for scientists for more than a century, and only in the last decade, thanks to the discovery of PIEZO proteins in 2010, have we started to understand how this type of mechanosensing functions at the molecular level [1–4].

In humans, PIEZO1 and PIEZO2 are mechanosensitive ion-channel proteins encoded by identically named genes. These proteins are 47% identical to each other but differ from other ion-channel proteins in their large size (PIEZO1 and PIEZO2 have 2,521 and 2,752 amino acid residues, respectively) and structure resembling a three-blade propeller [2–4].

PIEZO proteins, as a result of transduction, convert mechanical signals into biochemical cellular reactions. The mechanical action on the cell membrane ensures the passage of cations through the PIEZO channels. Ca²⁺ entry into cells serves as the starting point for many biochemical signals, such as the regulation of gene expression, cytoskeletal remodeling, and protein transport. Recently, accumulated data emphasize the importance of this family of ion-channel proteins in the regulation of physiological processes; however, many mechanisms remain unknown [1, 2, 4].

PIEZO1 is produced in erythrocytes, lungs, bladder, pancreas, and uterine endometrium. It plays an important role in cell adhesion by maintaining integrin activation in the regulation of pulmonary vascular permeability and pulmonary blood flow, micturition (regulates bladder compliance), and erythrocyte hydration.

PIEZO2 is expressed in the neurons of the spinal ganglia, lungs, gastrointestinal tract, skin, and muscles (muscle spindle and Golgi organ). Special afferent fibers (proprioceptive neurons) transmit mechanical sensations from the muscle spindle and Golgi tendon organ to the spinal cord. PIEZO2 deficiency in proprioceptive neurons leads to impaired coordination and pathological limb positions. The PIEZO2 channel is important for the sensation of airway expansion and subtle tactile sense. Both PIEZO1 and PIEZO2 are also found in joint chondrocytes [1].

A PIEZO1 mutation causes dehydrated congenital stomatocytosis, a rare form of hemolytic anemia, and lymphatic dysplasia. PIEZO2 mutations impair proprioception, tactile and pain sensitivity, and urination and cause scoliosis, hip dysplasia, congenital contractures, arthrogryposis, perinatal respiratory distress syndrome, and muscle weakness [2].

PIEZO2 expression in proprioceptive neurons is essential for normal spinal and hip development. In mouse models, PIEZO2 deficiency in proprioceptive neurons leads to the development of scoliosis and hip dysplasia [1, 2].

Recent studies have demonstrated that PIEZO2 mutations contribute to the development of distal arthrogryposis in various forms. Unlike amyoplasia (the most common form of congenital multiple arthrogryposis, clinically manifested by multiple contractures, aplasia or hypoplasia of the muscles, and occurring sporadically), distal forms of arthrogryposis are characterized by a predominance of hand and feet lesion and hereditary nature of the disease [5]. Decrease-of-function PIEZO2 mutations cause distal arthrogryposis with impaired proprioception and tactile sense (autosomal recessive inheritance). Gain-of-function PIEZO2 mutations result in distal arthrogryposis types 3 and 5 (autosomal dominant inheritance).

The work aimed to analyze publications containing information about PIEZO2 and its role in the development of distal forms of arthrogryposis

MATERIALS AND METHODS

The study presents the results of a literature search on PIEZO2 and its influence on the development of distal forms of arthrogryposis. The literature search was performed in the open electronic databases of PubMed, Cochrane Library, and eLibrary using the following keywords: PIEZO2 gene, mutations, distal arthrogryposis, distal arthrogryposis type 3, Gordon syndrome, distal arthrogryposis type 5, distal arthrogryposis with proprioception, and touch disorders. Forty international and Russian studies were extracted from 1969 to 2022, of which 23 were published over the last 10 years.

RESULTS AND DISCUSSION

Gain-of-function PIEZO2 mutations

Distal arthrogryposis type 3 (Gordon syndrome)

Gordon syndrome (DA3, GS, OMIM: 114300) is clinically characterized by camptodactyly, cleft palate, foot deformity, and autosomal dominant inheritance. The disease is caused by a heterozygous PIEZO2 mutation located on chromosome 18p11. This disease was first described by H. Gordon et al. in 1969 [6]. In the available literature, 28 cases of distal arthrogryposis type 3 have been reported (Table 1) [6–13].

Table 1. Clinical manifestations of distal arthrogryposis type 3

Authors of the study, year

Number of cases

Sex

Age, years

Cleft palate

Bifurcation of the uvula

Deformity of the auricles

Ptosis

Altered palpebral fissure

Small mouth

Micrognathia

Chest deformity

Spinal deformity

Short stature

Short neck

Camptodactyly

Transverse palmar sulcus

Syndactyly

Ulnar deviation of the hands

Equinovarus deformity of the feet

Mental retardation

Cryptorchidism

Gordon H. et al., 1969 [6]

0.2

Say B. et al., 1980 [7]

Robinow M. Johnson G.F., 1981 [13]

Hall J.G. et al., 1982 [8]

Ioan D.M. et al., 1993 [9]

Courtens W. et al., 1997 [13]

2.4

Wild A. et al., 2001 [10]

Botha S.J. et al., 2015 [11]

1.5

Hajela R. et al., 2015 [13]

0.1

Alisch F. et al., 2017 [12]

0.1

Roomaney I.A. et al., 2021 [13]

The main clinical aspects of Gordon syndrome are camptodactyly, equinovarus foot deformity, and short stature. In 42% of cases, patients have a cleft palate; in 6% of cases, they have bifurcated uvula. Some patients have hypotension and decreased muscle mass. In 6% of cases, patients have moderate mental retardation. Studies have also described cases of cryptorchidism in this disease [6, 12, 14, 15].

Clinical manifestations of distal arthrogryposis type 3 are presented in Table 1 and Figs. 1 and 2.

Fig. 1. Musculoskeletal pathologies in patients with distal arthrogryposis type 3

Fig. 2. Facial dysmorphism in patients with distal arthrogryposis type 3

Differential diagnostics of distal arthrogryposis type 3 should be performed with diseases such as the Aase–Smith syndrome (OMIM: 147800), Marden–Walker syndrome (MWS, OMIM: 248700), distal arthrogryposis type 5 (DA5, OMIM: 108145), Schwartz–Jampel syndrome (SJS1, OMIM: 255800), distal arthrogryposis type 1 (DA1, OMIM: 108120), and distal arthrogryposis type 2B (DA2B, OMIM: 601680) [15, 16].

Distal arthrogryposis type 5

Distal arthrogryposis type 5 (DA5, OMIM: 108145) is characterized by ocular abnormalities (most often ptosis, ophthalmoplegia, and/or strabismus) in combination with limb joint contractures. Patients have signs of facial dysmorphism such as hypomimia, triangular-shaped face, auricle deformity, deep-set eyes, and muscle rigidity (Fig. 3) [8, 15, 17–29]. Existing literature has described 41 cases of distal arthrogryposis type 5 (Table 2).

Fig. 3. Clinical manifestations of facial dysmorphism in patients with distal arthrogryposis type 5

Table 2. Clinical manifestations of distal arthrogryposis type 5

Authors of the study, year

Number of cases

Sex

Age, years

Short stature

Deep-set eyes

Ptosis

Impaired refraction

Ophthalmoparesis

Keratoconus

High-vaulted palate

Auricle deformity

Flattened facial expressiveness

Triangular-shaped face

Decreased muscle mass

Muscle rigidity

Stiffness of the spinal muscles

Short neck

Scoliosis

Camptodactyly

Absence of interphalangeal folds

Hand contracture

Wrist contracture

Contracture of the elbow joints

Contracture in the shoulder joints

Contracture in the hip joints

Contracture in the knee joints

Equinovar deformity of the feet

Heart pathology

Lung diseases

Chest deformity

Dimples on large joints

Hall J.G. et al., 1982 [8]

Lai M.M. et al., 1991 [17]

1.5

Schrander-Stumpel C.T. et al., 1993 [18]

Friedman B.D., Heidenreich R.A., 1995 [19]

Pallotta R. et al., 2000 [20]

12.5

14.5

Beals R.K., Weleber R.G., 2004 [21]

Sahni J. et al., 2004 [22]

Williams M.S. et al., 2007 [23]

Castori M. et al., 2009 [24]

Coste B. et al., 2013 [25]

Okubo M. et al., 2015 [26]

Zapata-Aldana E. et al., 2019 [27]

Serra G. et al., 2022 [28]

0.4

Oliwa A. et al., 2022 [29]

0.3

This disease is acquired in an autosomal dominant manner; for the first time, its genotype was identified by B. Coste et al. in 2013 [29]. A patient with similar clinical manifestations was first reported in 1939 by H.S. Altman and L.T. Davidson. Later B.D. Friedman and R.A. Heidenreich (1995) assessed the family history of the described patient and his son and regarded this case as distal arthrogryposis type 5 [8, 19].

An orthopedic examination revealed motion restriction in the spine, short neck, pectus excavatum, and scoliosis (often early progressing). In nearly half of the cases, patients have a short. A characteristic clinical sign of distal arthrogryposis type 5 is hand deformities, namely, finger contractures (camptodactyly), absence of folds in the projection of the interphalangeal joints, and clinodactyly of the fifth finger. Contractures of large joints of the extremities, more often the wrist and elbow and less often the shoulder, hip, and knee joints, were observed. The X-ray imaging of patients with distal arthrogryposis type 5 detects shortening of toes I and V, synostosis of the metacarpal and metatarsal bones, synostosis of the vertebrae, and scoliosis [26]. Other less common symptoms are toe syndactyly and cervical pterygium. Equinovarus deformity of the feet is characteristic (Fig. 4).

Fig. 4. Musculoskeletal pathologies in patients with distal arthrogryposis type 5

A distinctive clinical sign of distal arthrogryposis type 5 is an eye disorder, including ptosis, ophthalmoparesis, refraction disorders, degenerative changes in the retina, and optic nerve damage [25, 26]. A probable cause of ophthalmoparesis may be fibrosis of the eye muscles [21, 22] (Fig. 5).

Fig. 5. Eye pathologies in patients with distal arthrogryposis type 5

In this arthrogryposis type, respiratory disorders are registered in 35% of cases. R.K. Beals and R.G. Weleber (2004) described four generations of the same family who suffered from severe obstructive-restrictive pulmonary dysfunction [21]. According to S. Dai et al. (2018), patients with severe distal arthrogryposis type 5 require tracheostomy [30]. M.S. Williams et al. (2007) reported a case of pulmonary hypertension in this arthrogryposis type [23].

Differential diagnostics of distal arthrogryposis type 5 should be performed with Marden–Walker syndrome, Gordon syndrome, and other types of distal arthrogryposis [15].

Loss-of-function PIEZO2 mutations

Distal arthrogryposis with impaired proprioception and tactile sense

In 2016, A. Delle Vedove et al. (2016) described 10 patients from four families with distal arthrogryposis, who were experiencing impaired proprioception and tactile sense [31]. This disease was caused by a PIEZO2 mutation on chromosome 18p11 (OMIM: 613629). The authors concluded that PIEZO2 loss in afferent neurons in the spinal ganglia leads to impaired proprioception, muscle development, and function. This disease is inherited in an autosomal recessive manner [31].

In mouse experiments, complete deactivation of PIEZO2 caused a lethal outcome in the perinatal period. Mice with PIEZO2 protein loss in mechanosensory neurons were diagnosed with severe impairments in motor coordination and limb rigidity [32].

Since 2016, new cases of distal arthrogryposis with impaired proprioception and tactile sense have been described. Existing literature presented 23 cases of this disease (Table 3) [31, 33–40].

Table 3. Clinical manifestations of distal arthrogryposis with impaired proprioception and tactile sense

Authors of the study, year

Number of cases

Sex

Age, years

Respiratory failure

Feeding problems

Hypotonia

Delayed motor development

Delayed start of walking

Start walking

Lack of deep reflexes

Dysarthria

Decreased proprioception

Axonal sensory neuropathy

Impaired mental function

Facial dysmorphism

Hypomimia/ptosis

short stature

Progressive scoliosis

Joint hypermobility

Camptodactyly

Arachnodactyly

Deformity of the first finger

Congenital dysplasia /hip joint dislocation

Foot deformity

Delle Vedove A. et al., 2016 [31]

5 years

6 years

5 years

Does not go

8 years

5–6 years

Chesler A.T. et al., 2016 [33]

6–7 years

Mahmud A.A. et al., 2017 [34]

9 years

6 years

Does not go

Haliloglu G. et al., 2017 [35]

16 years

Behunova J. et al., 2018 [36]

3.5

Does not go

Yamaguchi T. et al., 2019 [37]

Oakley-Hannibal E. et al., 2020 [38]

2 years

Klaniewska M. et al., 2021 [39]

Does not go

2.7

Does not go

3.3

Does not go

Маркова Т.В. и др., 2021 [40]

Does not go

Pathogenic loss-of-function PIEZO2 mutations cause severe muscle hypotonia (90%), motor developmental delay (gait delay in 87% of cases), transient respiratory failure (39%), feeding problems in early infancy (43%), contractures of the joints of the upper and lower extremities, and progressive scoliosis. In the musculoskeletal system, feet and hand deformities (camptodactyly, arachnodactyly, and duckbill-shaped deformity of the first finger), short stature, joint hypermobility, and hip joint pathology (dysplasia or dislocation) are typical (Fig. 6).

Fig. 6. Musculoskeletal pathologies in patients with distal arthrogryposis and impaired proprioception and tactile sense

Impaired proprioception is the main clinical sign of this disease. Patients have impaired balance and coordination, tactile sensitivity, areflexia, and dysarthria, and axonal neuropathy was diagnosed in nerve conduction studies [31, 33, 35, 37, 39] (Fig. 7).

Fig. 7. Clinical manifestations in the nervous system of patients with distal arthrogryposis and impaired proprioception and tactile sense

In 17% of cases, patients have delayed cognitive functioning [31, 39].

CONCLUSION

This literature review revealed the importance of PIEZO2 in the regulation of various physiological processes in the human body. Mutations of this gene cause distal arthrogryposis types 3 and 5 and distal arthrogryposis with impaired proprioception and tactile sense. The rare incidence of this pathology and complexity of clinical diagnosis warrant a molecular genetic study to verify the disease and select the optimal treatment approach.

ADDITIONAL INFORMATION

Funding. The work was conducted within the State task of the Ministry of Health of Russia, Research & Development No. 121031700125-7.

Conflict of interest. The authors declare no conflict of interest.

Author contributions. V.V. Chernyavskaya-Khaukka developed the study design, reviewed the publications on the topic of the article, analyzed the material, and wrote the text of the manuscript. O.E. Agranovich developed the study design, reviewed the publications on the topic of the article, and edited the text of the manuscript.

All authors made a significant contribution to the study and preparation of the article, read and approved the final version before its publication.

About the authors

Varvara V. Chernyavskaya-Haukka

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Email: haukka90@mail.ru
ORCID iD: 0000-0002-6349-0559

MD, resident

Russian Federation, Saint Petersburg

Olga E. Agranovich

H. Turner National Medical Research Center for Сhildren’s Orthopedics and Trauma Surgery

Author for correspondence.
Email: olga_agranovich@yahoo.com
ORCID iD: 0000-0002-6655-4108
SPIN-code: 4393-3694
Scopus Author ID: 56913386600
ResearcherId: B-3334-2019
http://www.rosturner.ru/kl10.htm

MD, PhD, Dr. Sci. (Med.)

Russian Federation, Saint Petersburg

References

Szczot M, Nickolls AR, Lam RM, et al. The form and function of PIEZO2. Annu Rev Biochem. 2021;90:507–534. doi: 10.1146/annurev-biochem-081720-023244
Assaraf E, Blecher R, Heinemann-Yerushalmi L, et al. PIEZO2 expressed in proprioceptive neurons is essential for skeletal integrity. Nat Commun. 2020;11(1). doi: 10.1038/s41467-020-16971-6
Coste B, Mathur J, Schmidt M, et al. PIEZO1 and PIEZO2 are essential components of distinct mechanically activated cation channels. Science. 2010;330(6000):55–60. doi: 10.1126/science.1193270
Coste B, Xiao B, Santos JS, et al. PIEZO proteins are pore-forming subunits of mechanically activated channels. Nature. 2012;483(7388):176–181. doi: 10.1038/nature10812
Bamshad M, van Heest AE, Pleasure D. Arthrogryposis: a review and update. J Bone Joint Surg Am. 2009;91(Suppl 4):40–46. doi: 10.2106/JBJS.I.00281
Gordon H, Davies D, Berman M. Camptodactyly, cleft palate, and club foot. A syndrome showing the autosomal-dominant pattern of inheritance. J Med Genet. 1969;6(3):266–274. doi: 10.1136/jmg.6.3.266
Say B, Barber DH, Thompson RC, et al. The Gordon syndrome. J Med Genet. 1980;17(5). doi: 10.1136/jmg.17.5.405
Hall JG, Reed SD, Greene G. The distal arthrogryposes: delineation of new entities – review and nosologic discussion. Am J Med Genet. 1982;11(2):185–239. doi: 10.1002/ajmg.1320110208
Ioan DM, Belengeanu V, Maximilian C, et al. Distal arthrogryposis with autosomal dominant inheritance and reduced penetrance in females: the Gordon syndrome. Clin Genet. 1993;43(6):300–302. doi: 10.1111/j.1399-0004.1993.tb03822.x
Wild A, Schillians N, Kumar M, et al. Scoliosis in Gordon’s syndrome. Eur Spine J. 2001;10(5):458–460. doi: 10.1007/s005860100265
Botha SJ, Bütow KW. Gordon syndrome: literature review and a report of two cases. Cleft Palate Craniofac J. 2015;52(1):e18–22. doi: 10.1597/13-075
Alisch F, Weichert A, Kalache K, et al. Familial Gordon syndrome associated with a PIEZO2 mutation. Am J Med Genet A. 2017;173(1):254–259. doi: 10.1002/ajmg.a.37997
Roomaney IA, Walters J, Spencer C, et al. Gordon syndrome: dental implications and a case report. Spec Care Dentist. 2021;41(6):727–734. doi: 10.1111/scd.12615
Halal F, Fraser FC. Camptodactyly, cleft palate, and club foot (the Gordon syndrome). A report of a large pedigree. J Med Genet. 1979;16(2):149–150. doi: 10.1136/jmg.16.2.149
McMillin MJ, Beck AE, Chong JX, et al. Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5. Am J Hum Genet. 2014;94(5):734–744. doi: 10.1016/j.ajhg.2014.03.015
Becker K, Splitt M. A family with distal arthrogryposis and cleft palate: possible overlap between Gordon syndrome and Aase-Smith syndrome. Clin Dysmorphol. 2001;10(1):41–45. doi: 10.1097/00019605-200101000-00009
Lai MM, Tettenborn MA, Hall JG, et al. A new form of autosomal dominant arthrogryposis. J Med Genet. 1991;28(10):701–703. doi: 10.1136/jmg.28.10.701
Schrander-Stumpel CT, Höweler CJ, Reekers AD, et al. Arthrogryposis, ophthalmoplegia, and retinopathy: confirmation of a new type of arthrogryposis. J Med Genet. 1993;30(1):78–80. doi: 10.1136/jmg.30.1.78
Friedman BD, Heidenreich RA. Distal arthrogryposis type IIB: further clinical delineation and 54-year follow-up of an index case. Am J Med Genet. 1995;58(2):125–127. doi: 10.1002/ajmg.1320580207
Pallotta R, Ehresmann T, Fusilli P. Occurrence of Dandy-Walker anomaly in a familial case of distal arthogryposis type IIB. Am J Med Genet. 2000;95(5):477–481. doi: 10.1002/1096-8628(20001218)95:5<477::aid-ajmg13>3.0.co;2-m
Beals RK, Weleber RG. Distal arthrogryposis 5: a dominant syndrome of peripheral contractures and ophthalmoplegia. Am J Med Genet A. 2004;131(1):67–70. doi: 10.1002/ajmg.a.30289
Sahni J, Kaye SB, Fryer A, et al. Distal arthrogryposis type IIB: unreported ophthalmic findings. Am J Med Genet A. 2004;127A(1):35–39. doi: 10.1002/ajmg.a.20634
Williams MS, Elliott CG, Bamshad MJ. Pulmonary disease is a component of distal arthrogryposis type 5. Am J Med Genet A. 2007;143A(7):752–756. doi: 10.1002/ajmg.a.31648
Castori M, Rinaldi R, Barboni L, et al. Juvenile macular dystrophy and forearm pronation-supination restriction presenting with features of distal arthrogryposis type 5. Am J Med Genet A. 2009;149A(3):482–486. doi: 10.1002/ajmg.a.32668
Coste B, Houge G, Murray MF, et al. Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of distal arthrogryposis. Proc Natl Acad Sci USA. 2013;110(12):4667–4672. doi: 10.1073/pnas.1221400110
Okubo M, Fujita A, Saito Y, et al. A family of distal arthrogryposis type 5 due to a novel PIEZO2 mutation. Am J Med Genet A. 2015;167A(5):1100–1106. doi: 10.1002/ajmg.a.36881
Zapata-Aldana E, Al-Mobarak SB, Karp N, et al. Distal arthrogryposis type 5 and PIEZO2 novel variant in a Canadian family. Am J Med Genet A. 2019;179(6):1034–1041. doi: 10.1002/ajmg.a.61143
Serra G, Antona V, Cannata C, et al. Distal Arthrogryposis type 5 in an Italian family due to an autosomal dominant gain-of-function mutation of the PIEZO2 gene. Ital J Pediatr. 2022;48(1). doi: 10.1186/s13052-022-01329-z
Oliwa A, Hendson G, Longman C, et al. Lethal respiratory course and additional features expand the phenotypic spectrum of PIEZO2-related distal arthrogryposis type 5. Am J Med Genet A. 2022. doi: 10.1002/ajmg.a.63019
Dai S, Dieterich K, Jaeger M, et al. Disability in adults with arthrogryposis is severe, partly invisible, and varies by genotype. Neurology. 2018;90(18):e1596–e1604. doi: 10.1212/WNL.0000000000005418
Delle Vedove A, Storbeck M, Heller R, et al. Biallelic loss of proprioception-related PIEZO2 causes muscular atrophy with perinatal respiratory distress, arthrogryposis, and scoliosis. Am J Hum Genet. 2016;99(6):1406–1408. doi: 10.1016/j.ajhg.2016.11.009
Alper SL. Genetic diseases of PIEZO1 and PIEZO2 dysfunction. Curr Top Membr. 2017;79:97–134. doi: 10.1016/bs.ctm.2017.01.001
Chesler AT, Szczot M, Bharucha-Goebel D, et al. The role of PIEZO2 in human mechanosensation. N Engl J Med. 2016;375(14):1355–1364. doi: 10.1056/NEJMoa1602812
Mahmud AA, Nahid NA, Nassif C, et al. Loss of the proprioception and touch sensation channel PIEZO2 in siblings with a progressive form of contractures. Clin Genet. 2017;91(3):470–475. doi: 10.1111/cge.12850
Haliloglu G, Becker K, Temucin C, et al. Recessive PIEZO2 stop mutation causes distal arthrogryposis with distal muscle weakness, scoliosis and proprioception defects. J Hum Genet. 2017;62(4):497–501. doi: 10.1038/jhg.2016.153
Behunova J, GerykovaBujalkova M, Gras G, et al. Distal arthrogryposis with impaired proprioception and touch: description of an early phenotype in a boy with compound heterozygosity of PIEZO2 mutations and review of the literature. Mol Syndromol. 2019;9(6):287–294. doi: 10.1159/000494451
Yamaguchi T, Takano K, Inaba Y, et al. PIEZO2 deficiency is a recognizable arthrogryposis syndrome: a new case and literature review. Am J Med Genet A. 2019;179(6):948–957. doi: 10.1002/ajmg.a.61142
Oakley-Hannibal E, Ghali N, Pope FM, et al. A neuromuscular disorder with homozygosity for PIEZO2 gene variants: an important differential diagnosis for kyphoscoliotic Ehlers-Danlos syndrome. Clin Dysmorphol. 2020;29(1):69–72. doi: 10.1097/MCD.0000000000000304
Klaniewska M, Jedrzejowska M, Rydzanicz M, et al. Case report: further delineation of neurological symptoms in young children caused by compound heterozygous mutation in the PIEZO2 gene. Front Genet. 2021;12. doi: 10.3389/fgene.2021.620752
Markova TV, Dadali EL, Nikitin SS, et al. Clinical and genetic characteristics of distal arthrogryposis caused by mutations in the PIEZO2 gene. Neuromuscular Diseases. 2021;11(2):48–55. (In Russ.) doi: 10.17650/2222-8721-2021-11-2-48-55