Two missense STK11 gene variations impaired LKB1/adenosine monophosphate-activated protein kinase signaling in Peutz-Jeghers syndrome

Table 1 Spectrum of STK11 mutations and clinical characteristics of patients with Peutz-Jeghers syndrome

Proband family No.	Proband gender, age (yr)	Clinical features	Age at first discovery of polyps	Previous medicine history	Nucleotide alteration, amino acid alteration	Exon/Intron, mutation type	ACMG	PJS family history	Reproductive choice	Current Clinical outcome	Pedigree analysis
1	Man, 34	Pigmentation of skin and mucosa; multiple polyps	19	Intestinal polypectomy	c.180C>A (p.Tyr60Ter)	Exon1, nonsense	P	De novo	IVF-ET	The fetus had the same mutation and the pregnancy was terminated	Reject
2	Woman, 30	Pigmentation of skin and mucosa; multiple polyps	25	Polypectomy was performed in the stomach, colon and uterus	c.889A>G (p.Arg297Gly)	Exon7, missense	VUS	Yes, maternal. Mother, brother	PGT	The fetus was 5 wk+ and had a spontaneous abortion	Brother carries STK11 variation but father doesn’t
					c.1062C>G (p.Phe354Leu)	Exon 8, missense	LB
3	Man, 27	Pigmentation of skin and mucosa; multiple polyps	16	Multiple gastrointestinal polypectomy	c.733C>T (p.Leu245Phe)	Exon5, missense	VUS	De novo	PGT	The fetus was prenatally diagnosed as having no mutation and gave birth to a child	Parents had no STK11 variation
4	Man, 25	Pigmentation of skin and mucosa; multiple polyps	15	Multiple gastrointestinal polypectomy	c.250A>T (p.Lys84*)	Exon1, nonsense	P	De novo	PGT	Preoperative preparation for PGT	Parents had no STK11 variation
5	Woman, 35	Pigmentation on the face and lips; multiple polyps	19	Twice minimally invasive surgery for intestinal polyps and laparotomy operation	c.114_121delGCGCCGCA (p.Arg39Alafs*121)	Exon1, frame shift	P	Yes, paternal. Father, uncle, brother	PGT	The fetus was prenatally diagnosed as having no mutation and gave birth to a child	Mother and son had no STK11 variation
6	Woman, 33	Pigmentation on the lower lip, fingers, soles of the feet, and oral mucosa; multiple polyps	25	Polypectomy was performed in the small intestine and uterus	c.193G>T(p.Glu65*)	Exon1, nonsense	P	De novo	PGT	Preoperative preparation for PGT	Parents had no STK11 variation
7	Man, 45	Pigmentation on the lower lip, fingers, and oral mucosa; multiple polyps	22	Multiple gastrointestinal polypectomy	c.464+1G>A	Intron 3-4, splicing	LP	De novo	PGT	Preoperative preparation for PGT	Parents had no STK11 variation
8	Man, 23	Pigmentation on the lips	/	Laser treatment for hyperpigmentation at 19 yr, no polyps found on gastrointestinal endoscopy	c.734+3A>T	Intron 5-6, splicing	LP	Yes, paternal. Father, grandfather, sister, and niece	/	Unmarried, under consideration	Father had STK11 variation
9	Woman, 24	Pigmentation on the limbs and trunk; multiple polyps	13	Multiple gastrointestinal polypectomy; termination because fetal had STK11 mutation	c.734+2T>C	Intron 5-6, splicing	P	De novo	PGT	Preoperative preparation for PGT	Parents had no STK11 variation

ACMG: American Society for Medical Genetics and Genomics; P: Pathogenic; IVF-ET: In vitro fertilization-embryo transfer; VUS: Variant of uncertain significance; LB: Likely benign; PGT: Preimplantation genetic testing; LP: Likely pathogenic.