. 2022 Jan 18;12:803024. doi: 10.3389/fendo.2021.803024

Table 1.

Selenoprotein mutations affecting thyroid hormone metabolism defects (THMDs) and their clinical features.

Family # (Reference)	Mutations	Protein change	Thyroid hormone metabolism				Skeletal structure and growth	Muscular and neurological effects	Hearing and balance	Metabolic effects and others	Status
Family # (Reference)	Mutations	Protein change	FT₄	rT₃	FT₃	TSH				Metabolic effects and others	Status
*SECISBP2*
1 (70)	c.1619G>A	p.R540Q	↑	↑	↓	↑	Short stature, delayed bone age	–	Normal	–	Homozygous
2 (70)	c.1312A>T	p.K438X	↑	↑	↓	normal	Short stature, transient growth retardation	–	Normal	–	Compound heterozygous
	c.1283+29G>A, abnormal splicing	Frameshift
3 (76)	c.382C>T	p.R128X	↑	↑	↓	normal	Short stature, delayed bone age	–	–	–	Homozygous
4 (77)	c.358C>T	p.120X	↑	↑	↓	↑	Short stature, delayed bone age. Failure to thrive. Craniofacial dysmorphism. Bilateral clinodactyly, short fifth metacarpals. Kyphoscoliosis, leg asymmetry	Hypotonia, hyporeflexia, limited flexion of the neck. Symmetrical generalized peripheral sensitive neuropathy in the legs. Hip girdle weakness, waddling gait, Gower’s sign. Impaired motor coordination. Intellectual disability	Bilateral sensorineural hearing loss	Obesity. Protruding tongue. Left eye semiptosis	Compound heterozygous
4 (77)	c.2308C>T	p.R770X	↑	↑	↓	↑			Bilateral sensorineural hearing loss	Obesity. Protruding tongue. Left eye semiptosis	Compound heterozygous
5 (78)	c.668delT	p.F223F fs X32	↑	↑	normal	normal	Genu valgus, external rotation of the hip	Muscle weakness, reduced aerobic exercise capacity, reduced lung vital capacity. Abnormal spinal curvature, fatty infiltration. Delayed motor and speech developmental milestones	Bilateral sensorineural hearing loss. Secretory otitis media. Rotatory vertigo	Fatigue. Severe Raynaud disease. Azoospermia. Photosensitivity. Persistent reduction in rbc and total lymphocyte counts. Elevated fat mass index, increased insulin sensitivity	Compound heterozygous
5 (78)	c.881-155T>A, abnormal splicing	Frameshift	↑	↑	normal	normal	Genu valgus, external rotation of the hip				Compound heterozygous
6 (78)	c.2071T>C	p.C691R	↑	↑	↓	normal	Short stature, delayed development. Failure to thrive	Muscle weakness, hypotonia, lumbar spinal rigidity, nasal voice. Delayed motor milestones	Bilateral sensorineural hearing loss	Nonketotic hypoglycemia. Eosinophilic colitis. Elevated fat mass index, increased insulin sensitivity	Compound heterozygous
6 (78)	Intronic SNP, abnormal splicing	Frameshift	↑	↑	↓	normal	Short stature, delayed development. Failure to thrive		Bilateral sensorineural hearing loss		Compound heterozygous
7 (79)	c.1529_1541dupCCAGCGCCCACT	p.M515Q fs X48	↑	–	↓	normal	Short stature, delayed development. Failure to thrive	Delayed motor and intellectual milestones. Fatty infiltration. Intellectual disability	Bilateral conductive hearing loss. Secretory otitis media. Rotatory vertigo	Fatigue. Bilateral hyperopia, esotropia. Hypoplastic thyroid gland	Compound heterozygous
7 (79)	c.235C>T	p.Q79X	↑	–	↓	normal	Short stature, delayed development. Failure to thrive				Compound heterozygous
8 (80)	c.2344C>T	p.Q782X	↑	↑	↓	normal	Delayed development	Delayed motor and intellectual milestones. Intellectual disability’	Normal	–	Compound heterozygous
8 (80)	c.2045-2048 delAACA	p.K682 fs 683X	↑	↑	↓	normal	Delayed development		Normal	–	Compound heterozygous
9 (82)	c.589C>T	p.R197X	↑	↑	normal	normal	Short stature, delayed development. Failure to thrive	–	–	–	Compound heterozygous
9 (82)	c.2037G>T	p.E679D	↑	↑	normal	normal	Short stature, delayed development. Failure to thrive	–	–	–	Compound heterozygous
10 (81)	c.2045-2048	p.K267K fs X2	↑	↑	↓	normal	–	Leg weakness, Gowers’ sign. Fatty infiltration. Attention deficit disorder	–	Obesity, impaired glucose tolerance. Fatigue. Right eye ptosis	Homozygous
11 (82)	c.1588A>G	p.T530A	–	–	–	–	–	–	–	–	Compound heterozygous
11 (82)	c.1711C>T	p.Q571X	–	–	–	–	–	–	–	–	Compound heterozygous
12 (82)	c.283delT	p.Y95I fs X31	–	–	–	–	–	–	–	–	Compound heterozygous
12 (82)	c.589C>T	p.R197X	–	–	–	–	–	–	–	–	Compound heterozygous
*TRU-TCA1-1*
13 (88)	C65G		↑	↑	normal	normal	–	Muscle weakness	–	Fatigue. Abdominal pain.	Homozygous
**DIO2 and TSHR**
14 (89)	DIO2 c.274A>G	p.T92A	↓	–	↓	↑	–	–	–	Anorexia and weight gain. Hypothyroidism	Homozygous*
14 (89)	TSHR c.1349G>A	p.R450H	↓	–	↓	↑	–	–	–	Anorexia and weight gain. Hypothyroidism	Heterozygous*
15 (89)	DIO2 c.274A>G	p.T92A	↓	–	↓	↑	–	–	–	Thyroid goiter, congenital hypothyroidism	Homozygous
15 (89)	TSHR c.1574T>C	p.F525S	↓	–	↓	↑	–	–	–	Thyroid goiter, congenital hypothyroidism	Heterozygous
*DIO1*
16 (90)	c.282C>A	p.N94K	–	↑	↓**	↑	–	–	–	Down syndrome	Heterozygous
17 (90)	c.603G>A	p.M201I	–	↑	↓**	–	–	–	–	Resistance to TRH. Elevated cholesterol	Heterozygous

*The proband has a homozygous deiodinase type-2 (DIO2) mutation and a heterozygous thyroid-stimulating hormone receptor (TSHR) mutation, whereas his affected grandson has a heterozygous DIO2 mutation and a homozygous TSHR mutation.

**Free T₃ (FT₃) levels by themselves were never specified. The probands were tested for reverse T₃ (rT₃)/FT₃ ratio.