Table 1.
A summmary of the documented variants of the CTSC gene
| Variant | Amino acid change | Inheritance | Position | Ethnicity | Consang uinity | Clinical features | References | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLS | Hyperkeratosis | Periodon titis | Other features | |||||||||
| Palms | Soles | Extreme ties | ||||||||||
| Missense variant | ||||||||||||
| c.2 T > C | p.Met1Thr | homo | Exon 1 | Japanese | No | ( +) | ( +) | ( +) | ( +) | Severe | Ventricular septal defect | [52] |
| c.116G > C | p.Trp39Ser | homo | Exon 1 | Puerto Rican | Yes | ( +) | ( +) | ( +) | ( +) | Severe | Confluent parakeratosis, tortuous capillaries in the dermal papillae, psoriasis | [53] |
| c.117G > T | p.Trp39Cys | homo | Exon1 | Turkish | Yes | ( +) | ( +) | ( +) | ( +) | Severe | Iron deficiency anemia | [54] |
| c.203 T > G (c1) | p.Leu68Arg | cpd het (c.458C > T) | Exon 2 | Mexican | No | ( +) | ( +) | NA | NA | Severe | [50] | |
| c.203 T > G | p.Leu68Arg | homo | Exon 2 | Mexican | No | ( +) | ( +) | ( +) | ( +) | Severe/mild | Recurrent bacterial skin infections, recurrent folliculitis and furuncles | [50] |
| c.302G > C | p.Trp101Ser | homo | Exon 2 | Turkish | Yes | (-) | (-) | (-) | (-) | Aggressive | Hypodontia, taurodontism, molar-incisor hypomineralization, language delay with absence of sentence construction | [55] |
| c.380A > C (c2) | p.His127Pro | cpd het (c.96 T > G) | Exon 3 | French | No | ( +) | ( +) | ( +) | NA | Severe | [81] | |
| c.394C > G | p.Arg132Gly | homo | Exon 3 | Chinese | NA | ( +) | NA | NA | NA | Severe | Severe loss of alveolar bone | [87] |
| c.415G > A | p.Arg132Gly | homo | Exon 3 | Turkish | Yes | ( +) | (-) | ( +) | (-) | Severe | [54] | |
| c.415G > A (c3) | p.Gly139Arg | cpd het (c.1141del) | Exon 3 | American | No | ( +) | ( +) | ( +) | NA | Severe | [57] | |
| c.415G > A (c4) | p.Gly139Arg | cpd het (c.778 T > C) | Exon 3 | Chinese | No | ( +) | ( +) | ( +) | (-) | Early onset | [79] | |
| c.415G > A (c5) | p.Gly139Arg | cpd het (c.72C > A) | Exon 3 | NA | NA | ( +) | ( +) | ( +) | NA | Severe | [56] | |
| c.458C > T (c1) | p.Thr153Ile | cpd het (c.203 T > G) | Exon 3 | Mexican | No | ( +) | ( +) | NA | NA | Severe | [50] | |
| c.458C > T (c6) | p.Thr153Ile | cpd het (c.201_224del) | Exon 3 | Scottish | No | ( +) | ( +) | ( +) | (-) | Early onset | [99] | |
| c.503A > G | p.Tyr168Cys | homo | Exon 4 | European | No | ( +) | Atopic dermatitis | Several episodes of skin abscesses | NA | Severe juvenile | Repeated tonsillitis, allergy to grass pollen | [58] |
| c.587 T > C | p.Leu196Pro | homo | Exon 4 | Brazilian | Yes | ( +) | ( +) | ( +) | (-) | Severe | [59] | |
| c.706G > T (c7) | p.Asp236Tyr | cpd het (c.872G > A) | Exon 5 | Spanish | No | ( +) | ( +) | ( +) | NA | Severe | [51] | |
| c.716A > G (c8) | p.Asn239Ser | cpd het (c.757 + 1G > A) | Exon 5 | Chinese | No | ( +) | ( +) | ( +) | NA | Severe | Embedded teeth, physical retardation | [60] |
| c.739A > C (c9) | p.Ser247Arg | cpd het (c.1131 T > G) | Exon 5 | Chinese | No | ( +) | (-) | ( +) | (-) | Severe | Skin scars on the neck and abdomen | [89] |
| c.745G > T | p.Val249Phe | homo | Exon 5 | NA | Yes | ( +) | ( +) | ( +) | ( +) | Severe | [61] | |
| c.755A > T | p.Gln252Leu | homo | Exon 5 | NA | Yes | ( +) | ( +) | ( +) | ( +) | Severe | [61] | |
| c.763 T > A (c10) | p.Cys255Ser | cpd het (c.118del/ c.941 T > C) | Exon 6 | Chinese | No | ( +) | NA | NA | NA | NA | [90] | |
| c.763 T > C (c11) | p.Cys255Arg | cpd het (c.1015C > A) | Exon 6 | Chinese | No | ( +) | ( +) | ( +) | ( +) | Severe | Psoriasiform lesions on knees and elbows | [88] |
| c.776A > G (c12) | p.Tyr259Cys | cpd het (c.145C > T) | Exon 6 | Indian | Yes | ( +) | ( +) | ( +) | ( +) | NA | Absent lower central incisors | [62] |
| c.778 T > C (c4) | p.Ser260Pro | cpd het (c.415G > A) | Exon 3 | Chinese | No | ( +) | ( +) | ( +) | (-) | Early onset | [79] | |
| c.800 T > C (c13) | p.Leu267Pro | cpd het (c.1015C > T) | Exon 6 | Chinese | No | ( +) | ( +) | ( +) | ( +) | Severe | Propositus at the baseline | [63] |
| c.802G > A (c14) | p.Glu268Lys | cpd het (c.901G > A) | Exon 6 | Japanese | No | ( +) | ( +) | ( +) | (-) | NA | Chronic sinusitis, mild acanthosis and hypogranulosis with focal hypergranulosis around the eccrine duct pores | [92] |
| c.815G > C (c15) | p.Arg272Pro | cpd het (c.1141del) | Exon 7 | French | No | ( +) | ( +) | ( +) | NA | Severe | [81] | |
| c.815G > C | p.Arg272Pro | homo | Exon 6 | NA | Yes | ( +) | ( +) | ( +) | ( +) | Severe | [61] | |
| c.815G > C | p.Arg272Pro | homo | Exon 6 | Belgian | No | ( +) | ( +) | ( +) | NA | Severe prepubertal | [71] | |
| c.815G > A (c16) | p.Arg272His | cpd het (c.1235A > G) | Exon 6 | NA | Yes | (-) | (-) | (-) | (-) | Prepubertal | [56] | |
| c.824C > T (c17) | p.Thr275Ile | cpd het (c.1040A > G) | Exon 6 | Chinese | No | ( +) | ( +) | ( +) | ( +) | Severe | Recurrent pyogenic skin infection, tinea cruris on the thighs, numerous scarring lesion on the buttocks, thigh and calves, loss of majority of dentition, high serum IgE | [91] |
| c.851G > A (c18) | p.Ser284Asn | cpd het (c.113_116del) | Exon 6 | Chinese | No | ( +) | ( +) | ( +) | ( +) | Early onset | [79] | |
| c.854C > T | p.Pro285Leu | homo | Exon 6 | Moroccan | Yes | ( +) | ( +) | ( +) | NA | Late onset aggressive | [39] | |
| c.857A > G | p.Gln286Arg | homo | Exon 6 | Indian | Yes | HMS | NA | NA | NA | Premature periodontal destruction | [99] | |
| c.872G > A (c7) | p.Cys291Tyr | cpd het (c.706G > T) | Exon 6 | Spanish | No | ( +) | ( +) | ( +) | NA | Severe | [51] | |
| c.880 T > C | p.Tyr294His | homo | Exon 6 | Spanish | No | ( +) | ( +) | ( +) | NA | Severe early onset | [65] | |
| c.898G > A (c19) | p.Gly300Ser | cpd het (c.1340A > G) | Exon 7 | Vietnamese | No | ( +) | ( +) | ( +) | (-) | Severe early onset | [99] | |
| c.899G > A | p.Gly300Asp | homo | Exon 7 | Arabian | Yes | ( +) | NA | NA | NA | NA | Primary ciliary dyskinesia, loss of primary teeth, nail dystrophy | [66] |
| c.901G > A | p.Gly301Ser | homo | Exon 7 | NA | Yes | ( +) | ( +) | ( +) | NA | Severe | [61] | |
| c.901G > A (c14) | p.Gly301Ser | cpd het (c.802G > A) | Exon 7 | Japanese | No | ( +) | ( +) | ( +) | (-) | NA | [92] | |
| c.902G > T | p.Gly301Val | homo | Exon 7 | Iranian | Yes | ( +) | ( +) | ( +) | ( +) | Severe early onset | [99] | |
| c.910 T > A | p.Tyr304Asn | homo | Exon 7 | Panamanian | Yes | ( +) | ( +) | ( +) | (-) | Early onset | Retinitis pigmentosa | [99] |
| c.923G > A (c20) | p.Gly308Glu | cpd het (c.890G > T) | Exon 7 | Italian | No | ( +) | ( +) | ( +) | NA | Early onset—slow progression | Recurrent pyoderma, scarring lesion over the buttocks, thighs, and calves, occasional subcutaneous fat herniation | [67] |
| c.935A > G | p.Gln312Arg | homo | Exon 7 | NA | NA | ( +) | ( +) | ( +) | NA | severe | [56] | |
| c.941 T > C (c10) | p.Phe314Ser | cpd het (c.118del / c.763A > T) | Exon 7 | Chinese | No | ( +) | NA | NA | NA | NA | [90] | |
| c.947 T > C | p.Leu316Pro | homo | Exon 7 | Latin American | Yes | ( +) | ( +) | ( +) | NA | Early onset | Premature tooth loss | [69] |
| c.947 T > G (c21) | p.Leu316Arg | cpd het (c.1268G > C) | Exon 7 | German | No | ( +) | ( +) | ( +) | NA | Aggressive | [68] | |
| c.956A > G | p.Glu319Gly | homo | Exon 7 | Iranian | Yes | ( +) | ( +) | ( +) | (-) | Early onset | [99] | |
| c.1010G > C | p.Cys337Ser | homo | Exon 7 | Latin American | Yes | ( +) | ( +) | ( +) | NA | Early onset | Premature tooth loss | [69] |
| c.1015C > T | p.Arg339Cys | homo | Exon 7 | NA | Yes | ( +) | ( +) | ( +) | NA | Severe | [61] | |
| c.1015C > T (c13) | p.Arg339Cys | cpd het (c.800 T > C) | Exon 7 | Chinese | No | ( +) | ( +) | ( +) | ( +) | Severe | [63] | |
| c.1015C > A (c11) | p.Arg339Ser | cpd het (c.763 T > C) | Exon 7 | Chinese | No | ( +) | ( +) | ( +) | ( +) | Severe | [88] | |
| c.1019A > G | p.Tyr340Cys | homo | Exon 7 | Turkish | Yes | ( +) | ( +) | ( +) | ( +) | Severe | Gluteal abscess, atopic dermatitis, elevated IgE, asthma | [54] |
| c.1040A > G | p.Tyr347Cys | homo | Exon 7 | Jordanian | Yes | (-) | (-) | (-) | (-) | Prepubertal | [99] | |
| c.1040A > G (c17) | p.Tyr347Cys | cpd het (c.824C > T) | Exon 7 | Chinese | No | ( +) | ( +) | ( +) | ( +) | Severe | [91] | |
| c.1040A > G (c22) | p.Tyr347Cys | cpd het (c.754C > T) | Exon 7 | Chinese | No | ( +) | ( +) | ( +) | ( +) | Mild | [93] | |
| c.1156G > C (c23) | p.Gly386Arg | cpd het (exons 3–7 deletion) | Exon 7 | Caucasian | No | ( +) | ( +) | ( +) | NA | Severe | Keratoderma, multiple cutaneous abscess formed | [70] |
| c.1213C > A | p.His405Asn | homo | Exon 7 | Pakistanis | Yes | ( +) | ( +) | ( +) | ( +) | Severe prepubertal | [71] | |
| c.1214A > G | p.His405Arg | homo | Exon 7 | Iranian | Yes | ( +) | ( +) | ( +) | NA | Aggressive | [39] | |
| c.1235A > G (c16) | p.Tyr412Cys | cpd (c.815G > A) | Exon 7 | NA | Yes | (-) | (-) | (-) | (-) | Prepubertal | [56] | |
| c.1268G > C (c21) | p.Trp423Ser | cpd het (c.947 T > G) | Exon 7 | German | No | ( +) | ( +) | ( +) | NA | Aggressive | [68] | |
| c.1287G > C (c24) | p.Trp429Cys | cpd het (c.1056del) | Exon 7 | French | No | ( +) | ( +) | ( +) | NA | Severe | [81] | |
| c.1337A > C | p.Asp446Ala | homo | Exon 7 | Cambodian | No | ( +) | ( +) | ( +) | ( +) | Aggressive | [137] | |
| c.1340A > G | p.Glu447Gly | homo | Exon 7 | NA | No | ( +) | ( +) | ( +) | NA | Severe | [56] | |
| **c.1340A > G (c19) | p.Glu447Gly | cpd het (c.898G > A) | Exon 7 | Vietnamese | No | ( +) | ( +) | ( +) | (-) | Severe early onset | [99] | |
| Nonsense variant | ||||||||||||
| c.72C > A | p.Cys24* | homo | Exon 1 | Moroccan | Yes | ( +) | ( +) | ( +) | NA | Severe | [81] | |
| c.72C > A (c5) | p.Cys24* | cpd het (c.415G > A) | Exon 1 | NA | NA | ( +) | ( +) | ( +) | NA | Severe | [56] | |
| c.90C > A | p.Cys30* | homo | Exon 1 | Thai | No | ( +) | ( +) | ( +) | ( +) | Mild | Severe infection | [73] |
| c.96 T > G (c2) | p.Tyr32* | cpd het (c.380A > C) | Exon 1 | French | No | ( +) | ( +) | ( +) | NA | Severe | [81] | |
| c.145C > T (c12) | p.Gln49* | cpd het (c.776A > G) | Exon 1 | Indian | Yes | ( +) | ( +) | ( +) | ( +) | NA | [62] | |
| c.145C > T | p.Gln49* | homo | Exon 1 | Indian | No | ( +) | ( +) | ( +) | NA | Premature | [85] | |
| c.205C > T | p.Gln69* | homo | Exon 2 | Indian | Yes | ( +) | ( +) | ( +) | ( +) | Premature | [85] | |
| c.322A > T (c25) | p.Lys108* | cpd het (c.436del) | Exon 3 | German | No | ( +) | ( +) | ( +) | NA | Late onset aggressive | [39] | |
| c.322A > T (c26) | p.Lys108* | cpd het (c.504C > G) | Exon 3 | Italian | No | ( +) | ( +) | ( +) | ( +) | NA | Tooth mobility, bone loss, tooth and skin abscess | [74] |
| c.504C > G (c26) | p.Tyr168* | cpd het (c.322A > T) | Exon 4 | Italian | No | ( +) | ( +) | ( +) | ( +) | NA | [74] | |
| c.544C > T (c27) | p.Gln182* | cpd het (110kb deletion) | Exon 4 | Chinese | No | ( +) | ( +) | ( +) | (-) | Severe | [86] | |
| c.555G > A | p.Trp185* | homo | Exon 4 | Brazilian | Yes | ( +) | ( +) | ( +) | ( +) | Early onset | [94] | |
| c.628C > T | p.Arg210* | homo | Exon 4 | NA | Yes | ( +) | ( +) | ( +) | NA | Severe | [61] | |
| c.628C > T(c28) | p.Arg210* | cpd het (c.1286G > A) | Exon 4 | Turkish | NA | ( +) | ( +) | ( +) | NA | Ealry onset | Loss of primary incisors and right mandibular first molar | [76] |
| c.704G > A | p.Trp235* | homo | Exon 5 | Iranian | Yes | ( +) | ( +) | ( +) | (-) | Early onset | [99] | |
| c.711G > A | p.Asp237* | homo | Exon 5 | Egyptian | No | NA | NA | NA | NA | NA | NA | |
| c.748C > T | p.Arg250* | homo | Exon 5 | Turkish | Yes | ( +) | ( +) | ( +) | ( +) | Early onset | [99] | |
| c.754C > T (c22) | p.Gln252* | cpd het (c.1040A > G) | Exon 5 | Chinese | No | ( +) | ( +) | ( +) | ( +) | Mild | [93] | |
| c.856C > T | p.Gln286* | homo | Exon 6 | Turkish | Yes | ( +) | ( +) | ( +) | ( +) | Early onset | [75] | |
| c.912C > A | p.Tyr304* | homo | Exon 7 | Indian | No | ( +) | ( +) | ( +) | NA | Severe | [85] | |
| c.1131 T > G (c9) | p.Tyr377* | cpd het (c.739A > C) | Exon 7 | Chinese | No | ( +) | (-) | ( +) | (-) | Severe | [89] | |
| c.1269G > A | p.Trp423* | homo | Exon 7 | Sri Lanka | Yes | ( +) | NA | NA | NA | Aggressive | Mild skin findings | [39] |
| c.1286G > A | p.Trp429* | homo | Exon 7 | Turkish | Yes | ( +) | ( +) | ( +) | ( +) | Early onset | [99] | |
| c.1286G > A (c28) | p.Trp429* |
cpd het (c.628C > T) |
Exon 7 | Turkish | NA | ( +) | ( +) | ( +) | NA | Early onset | [76] | |
| c.1287G > A | p.Trp429* | homo | Exon 7 | Turkish | Yes | ( +) | ( +) | ( +) | ( +) | Early onset | [75] | |
| c.1339G > T | p.Glu447* | homo | Exon 7 | Portuguese | Yes | ( +) | ( +) | ( +) | NA | Mild localized chronic | Atypical PLS (mild hyperkeratosis, high susceptibility to severe infection) | [95] |
| Splice-site variant | ||||||||||||
| c.319-1G > A | homo | Intron 2 | Jordanian | Yes | ( +) | ( +) | ( +) | NA | Severe | Type 1 oculocutaneous albinism, recurrent tonsillitis, respiratory tract infection, pyoderma, onychogryphosis, focal parakeratosis, hypergranulosis, acanthosis (having TYR: c.817G > C (p.W272C) | [64] | |
| c.319-1G > T | homo | Intron 2 | Iranian | Yes | ( +) | ( +) | ( +) | ( +) | Severe | [78] | ||
| c.485-1G > A | homo | Intron 3 | NA | Yes | ( +) | ( +) | ( +) | ( +) | Severe | [61] | ||
| c.757G > A | p.Ala253fs | homo | Exon 5 | Moroccan | Yes | ( +) | ( +) | ( +) | NA | Severe | [70] | |
| c.757 + 1G > A (c8) | cpd het (c.716A > G) | Intron 5 | Chinese | No | ( +) | ( +) | ( +) | NA | Severe | [60] | ||
| c.890G > T(c20) | p.Gly297Val (predicted splice site) | cpd het (c.923G > A) | Intron 6 | Italian | No | ( +) | ( +) | ( +) | NA | Early onset (slow progression) | [67] | |
| Indel (insertion-deletion) variant | ||||||||||||
| c.21del | p.Leu7fs | homo | Exon 1 | Pakistani | Yes | ( +) | ( +) | ( +) | NA | Severe gingivitis | Mild cutaneous phenotype | [77] |
| **c.106_108del | p.Leu36del | homo | Exon 1 | Iranian | Yes | ( +) | ( +) | ( +) | NA | Aggressive | [78] | |
| **c.113_116del (c18) | p.Thr38fs | cpd het (c.851G > A) | Exon 1 | Chinese | No | ( +) | ( +) | ( +) | ( +) | Early onset | [79] | |
| **c.118del (c10) | p.Val40fs | cpd het (c.763A > T/ c.941 T > C) | Exon 1 | Chinese | No | ( +) | NA | NA | NA | NA | [90] | |
| **c.181dup | p.Glu61fs | Homo | Exon 2 | NA | NA | ( +) | ( +) | ( +) | NA | Severe | [56] | |
| c.190_191insA (c29) | p.Val64fs | cpd het (c.1211_1212delA) | Exon 2 | Chinese | No | ( +) | ( +) | ( +) | (-) | Severe | [60] | |
| **c.201_224del (c6) | p.Leu68_Tyr75del | cpd het (c.458C > T) | Exon 2 | Scottish | No | ( +) | ( +) | ( +) | (-) | Early onset | [99] | |
| c.267_268del | p.Asn89fs | homo | Exon 2 | Brazilian | Yes | ( +) | ( +) | ( +) | ( +) | Severe early onset | [80] | |
| c.315dup | p.Lys106fs | homo | Exon 2 | Japanese | Yes | ( +) | ( +) | ( +) | ( +) | (-) | Recurrent pyogenic skin infection, tinea cruris on the thighs, numerous scarring lesion on the buttocks, thigh and calves, loss of majority of dentition, high serum IgE | [83] |
| **c.360_362dup | p.Thr121dup | homo | Exon 3 | Iranian | Yes | ( +) | ( +) | ( +) | NA | Severe | Susceptibility to infections | [96] |
| c.436delT (c25) | p.Ser146fs | cpd het (c.322A > T) | Exon 3 | German | No | ( +) | ( +) | ( +) | NA | Late onset aggressive | [39] | |
| c.445_446insATGT | p.Val149fs | homo | Exon 3 | Bengali | Yes | ( +) | ( +) | ( +) | (-) | Early onset | [99] | |
| c.566_572del | p.Thr189fs | homo | Exon 4 | German | Yes | (-) | (-) | (-) | (-) | Prepubertal | [68] | |
| **c.566_572del | p.Thr189fs | homo | Exon 4 | Hungarian | NA | ( +) | ( +) | ( +) | (-) | Severe | Circumscribed erythema, mild hyperkeratosis | [97] |
| c.566_572del | p.Thr189fs | homo | Exon 4 | Russian | No | ( +) | ( +) | ( +) | NA | Severe | [39] | |
| c.622dup | p.His208fs | homo | Exon 4 | Turkish | Yes | ( +) | ( +) | ( +) | ( +) | Early onset | [99] | |
| c.629_630del | p.Arg210fs | homo | Exon 4 | Indian | No | ( +) | ( +) | ( +) | ( +) | Severe | [82] | |
| **c.712_725del | p.Arg238fs | homo | Exon 5 | Algerian | Yes | ( +) | ( +) | ( +) | NA | Severe | [81] | |
| **c.984_990del | p.Ser329fs | homo | Exon 7 | French | Yes | ( +) | ( +) | ( +) | NA | Severe | [81] | |
| c.1028_1029del | p.Ser343* | homo | Exon 7 | Turkish | Yes | ( +) | ( +) | ( +) | ( +) | Early onset | [75] | |
| c.1047del | p.Gly350fs | homo | Exon 7 | Turkish | Yes | ( +) | ( +) | ( +) | ( +) | Early onset | [75] | |
| c.1056del (c24) | p.Tyr352fs | cpd het (c.1287G > C) | Exon 7 | French | Yes | ( +) | ( +) | ( +) | NA | Severe | [81] | |
| c.1141del | p.Leu381fs | homo | Exon 7 | Italian | No | ( +) | ( +) | ( +) | ( +) | Severe | [74] | |
| c.1141del (c15) | p.Leu381fs | cpd het (c.815G > C) | Exon 7 | French | No | ( +) | ( +) | ( +) | NA | Severe | [81] | |
| c.1141del (c3) | p.Leu381fs | cpd het (c.415G > A) | Exon 7 | American | No | ( +) | ( +) | ( +) | NA | Severe | [57] | |
| c.1211_1212del (c29) | p.Asn404fs | cpd het ( c.190_191insA) | Exon 7 | Chinese | No | ( +) | ( +) | ( +) | (-) | Severe | [60] | |
| c.1213_1215del | p.His405del | homo | Exon 7 | Indian | Yes | ( +) | ( +) | ( +) | ( +) | Severe | [82] | |
| Gross deletion variant | ||||||||||||
| NC_000011.9:g.88032292_88142997del (c27) | cpd het (c.544C > T) | Exon 1–5 | Chinese | No | ( +) | ( +) | ( +) | (-) | Severe | [86] | ||
| Intragenic exons 3–7 deletion (c23) | cpd het (c.1156G > C) | Exon 3–7 | Caucasian | No | ( +) | ( +) | ( +) | NA | Severe | [70] | ||
| NC_000011.9:g.88016961_88165581del | homo | Deletion | NA | No | ( +) | ( +) | ( +) | ( +) | Severe prepubertal | [98] | ||
| Regulatory variant | ||||||||||||
| c.-55C > A | homo | 5'-UTR | Slovenian | No | ( +) | ( +) | ( +) | ( +) | Severe | Diffuse transgredient PPK | [84] | |
PLS, Papillon–Lefèvre syndrome; HMS, Haim–Munk Syndrome; homo, homozygous; cpd het, compound heterozygous; NA, not available; (c1), (c2), (c3), …denote individuals who carry the compound heterozygous variants. The variants listed in the table represent the initially reported variants. ** The variants were reformatted from the original articles according to the Human Genome Variation Society (HGVS)