A novel missense variant in LAMC1 identified in a POI family by whole exome sequencing

Figures & data

Figure 1. Identification of the missense variant of LAMC1 in the POI family. (a) Pedigree of the family with POI. Filled black symbols represent affected members. Arrow denotes the proband. (b) The chromatogram of the missense variant c.3281A > T (p.D1094V) of LAMC1 in the patient and his parents. The arrow denotes the variant site.

Table 2. Hormonal characteristics of the proband.

NO.	Period	FSH (IU/L)	LH (IU/L)	E2 (pmol)
1	M3	29.15	8.33	108
2	M3	25.62	8.02	160

Abbreviation: M3, the third day of menstruation; FSH, Follicle-stimulating hormone; LH, Luteinizing hormone; E2, Estradiol.

Table 1. LAMC1-specific primers used for Sanger sequencing.

ID	Sequence	Length (bp)
LAMC1-F	ACATTCCTTGGGTGTCTT	459
LAMC1-R	TTTCAATCAACCGCTCTG

Figure 2. Bioinformatics analysis of the identified missense variant of LAMC1. (a) The location of the variant in the intron-exon structure of LAMC1 and the protein domain map of LAMC1. The missense variant (c.3281A > T, p.D1094V) of LAMC1 is located in the domain I and II. (b) Amino acid alignment of the LAMC1 protein from several organisms. The position of Asp1094 residue (highlighted by a black box) was highly conserved among different species.

Table 3. Biological analysis of the LAMC1 c.3281A > T variant.

Chromosome Position	Gene Variant	Amino acid change	Frequency^$	Gene Variant				ACMG Classification
				SIFT	PP2	MT	CADD
chr1: 183099479	c.3281A > T	p.D1094V	absent	D	P	D	26.5	VUS

^$ Frequency in overall population/East Asian population in gnomAD.

Abbreviation: SIFT, Sorts Intolerant from Tolerant (D, damaging); PP2, Polyphen-2 (P, possibly damaging); MT, MutationTaster (D, disease-causing); CADD, Combined Annotation-Dependent Depletion.

Data availability statement

All data used during the study are available from the corresponding author on reasonable request.