Table 7 Genes and chromosomal loci linked to non-syndromic familial non-medullary thyroid cancer

MAP2K5

15q23

34 families with two first-degree relatives with PTC (no syndromic FNMTC). Whole exome and target gene sequencing for candidate variants.

Ye et al. (2019) [86]

PLCB1

20p12.3

Genome wide linkage analysis and next generation sequencing performed in a family with MNG that was likely to progress to PTC as seen in some family members. An intronic PLCB1 InDel was found in all affected members.

Bakhsh et al. (2018) [87]

BROX

1q41

Whole-exome sequencing of PTC patients from five families. Two BROX variants were observed in two of the families.

Pasquali et al. (2021) [88]

POT1

7q31.33

Whole exome sequencing of five affected family members with melanoma and thyroid cancer revealed a new mutation in POT1. POT1 is involved with the telomere shelterin complex that controls telomere protection.

Wilson et al. (2017) [89]

A low frequency variant in POT1 was found in childhood cancer survivors that developed thyroid cancer.

Richard et al. (2020) [90]

A POT1 variant causes telomere dysfunction in a family affected only by FNMTC.

Srivastava et al. (2020) [91]

ATM

11q22.3

Whole-genome sequencing and genome-wide linkage analysis in 17 FNMTC families. ATM variant was identified in two families.

Wang et al. (2019) [92]

CHEK2

22q12.1

Whole-genome sequencing and genome-wide linkage analysis in 17 FNMTC families. A CHEK2 (breast and prostate cancer susceptibility gene) variant was identified in one family.

Wang et al. (2019) [92]

NOP53

19q13.33

Exome sequencing in a family with five cases of NSFNMTC and 44 additional families with FNMTC showed a low-penetrance germline variant of NOP53 with increased levels in tumour samples of the affected cases.

Orois et al. (2019) [93]

NDUFA13/ GRIM-19

19p13.11

A germline mutation was found in a patient with Hurthle cell PTC. No Grim-19 mutations were observed in familial Hurthle cell tumours. GRIM-19 is involved in mitochondrial metabolism.

Máximo et al. (2005) [94]

TIMM44

19p13.2

Screening of 14 candidate genes in the linkage region of affected TCO members from 8 FNMTC families. TIMM44 is a mitochondrial inner membrane translocase.

Bonora et al. (2006) [95]

SRRM2

16p13.3

Whole exome sequencing in a PTC family with six affected first- or second-degree relatives detected a germline variant in SRRM2. This gene is involved in RNA splicing, with aberrant alternative splicing in affected individuals.

Tomsic et al. (2015) [96]

ANXA3

4q21.21

Whole exome sequencing in three Brazilian families with familial PTC yielded seven new genes with implication in hereditary PTC.

Sarquis et al. (2020) [97]

NTN4

12q22

SERPINA1

14q32.13

FKBP10

17q21.2

PLEKHG5

1p36.31

P2RX5

17p13.2

SAPCD1

6p21.33

Unknown

8q24 (PTCSC1)

Genome wide linkage analysis in a large family with PTC and melanoma.

He et al. (2009) [98]

Unknown

4q32

Linkage analysis and targeted deep sequencing identified an ultra-rare mutation (SNP) in chromosome 4q32 in a large pedigree affected by FNMTC.

He et al. (2013) [99]

Unknown

6q22

Linkage analysis in 38 FNMTC families revealed, 6q22 (Maximum LOD of 3.3) displayed linkage.

Suh et al. (2009) [100]

Unknown

1q21 (fPTC,PRN)

Linkage analysis in a large three-generation familial PTC kindred, maximum LOD of + 3.58.

Malchoff et al. 2000) [101]

Linkage analysis in forty-nine affected cases with FNMTC, maximum LOD of + 3.04.

Suh et al. (2009) [100]

Unknown

14q32 (MNG1)

Linkage analysis in a Canadian family with 18 cases of MNG (2 of which were also diagnosed with PTC). Maximum LOD of 3.8.

Bignell et al. (1997) [102]

Unknown

2q21 (NMTC1)

Linkage analysis in a large Tasmanian pedigree with PTC. Multipoint heterogeneity LOD of 3.07.

Mckay et al. (2001) [103]

Linkage analysis in 10 FNMTC families. Linkage evident at both TCO and NMTC (LOD = 1.56 and 2.85, respectively)

Mckay et al. (2004) [104]

Loss of heterozygosity (LOH) was analyzed at 2q21 and 19p13.2 in 9 FNMTC families. Two of the fourteen tumours displayed LOH at 2q21 (14%).

Prazeres et al. (2008) [105]

Unknown

8p23.1-p22 (FTEN)

Linkage analysis in a Portuguese family affected by PTC and benign thyroid lesions detected a linkage with 8p23.1-p22, Maximum haplotype-based LOD of 4.41.

Cavaco et al. (2008) [106]

Unknown

19q13.2 (TCO)

Linkage analysis in a French pedigree affected by PTC and MNG lead to mapping chromosome 19p13.2 to TCO (thyroid tumours with cell oxyphilia). Maximum LOD of 3.01.

Canzian et al. (1998) [107]

Linkage analysis in one family with PTC and MNG. Maximum LOD of 1.54.

Bevan et al. (2001) [108]

Linkage analysis in ten families affected by PTC and MNG. Maximum LOD of 1.56.

McKay et al. (2004) [104]

Loss of heterozygosity (LOH) was analyzed at 19p13.2 in 9 FNMTC families. Eight of the fourteen tumours displayed LOH at 19p13.2 (57%).

Prazeres et al. (2008) [105]