Table 1.
Pathogenic LEP, LEPR, and MC4R mutations identified in probands from SOPP cohort in relation to subethnic groups
| Mutation | Type of mutation | 1st reported/novel | REVEL score | No. probands | Subethnicity | |
|---|---|---|---|---|---|---|
| LEP | c.398del (p.G133Valfs∗15) | frameshift | Montague et al.1 | – | 62 | Arain (n = 54), Rajput, Mughal, Gazar, Jutt (n = 2), Tamboo, N/Aa (n = 2) |
| LEP | c.313C>T (p.R105W) | missense | Strobel et al.17 | 0.686 (Dam) | 1 | Sahotra |
| LEP | c.-28-16_-3del | splice site | Saeed et al.8 | – | 2 | Mashki, Rajput |
| LEP | c.-29 + 1G>C | splice site | Saeed et al.8 | – | 4 | Sheikh (n = 2), Sahotra, Lotay |
| LEP | c.298G>A (p.D100N) | missense | Saeed et al.8 | 0.610 (Dam) | 1 | Sheikh |
| LEP | c.309C>A (p.N103K) | missense | Mazen et al.18 | 0.523 (Dam) | 2 | Arain, Rehmani |
| LEP | c.314G>A (p.R105Q) | missense | Saeed et al.16 | 0.467 (Uncer)b | 1 | Ansari |
| LEP | c.350G>A (p.C117Y) | missense | Saeed et al.8 | 0.33 (Uncer)b | 2 | Warraich (n = 2) |
| LEP | c.104_106del (p.I35del) | in-frame deletion | Fatima et al.19 | – | 5 | Rajput (n = 2), Jutt (n = 2), Bhatti |
| LEP | c.417delC (p.Y140Tfs∗8) | frameshift | Saeed et al.16 | – | 2 | Syed Bukhari, Jutt |
| LEP | c.481_482del (p.L161Gfs∗10) | frameshift | Fatima et al.19 | – | 1 | Jutt |
| LEPR | c.2396-1G>T | splice site | Saeed et al.10 | – | 7 | Jutt, Rajput (n = 4), Ansari (n = 2) |
| LEPR | c.2396-2A>G | splice site | Saeed et al.16 | – | 2 | Rajput, Bayi |
| LEPR | c.704-1G>A | splice site | Saeed et al.16 | – | 3 | Ansari, Bhatti, Khansani |
| LEPR | c.2213-3C>G | splice site | Saeed et al.16 | – | 1 | Kakazai |
| LEPR | c.994 + 2T>C | splice site | – | – | 1 | Mughal |
| LEPR | c.2T>C (p.?) | start loss | Saeed et al.16 | – | 1 | Awan |
| LEPR | c.1674G>A (p.W558∗) | nonsense | Saeed et al.10 | – | 2 | Siddiqui, Sheikh |
| LEPR | c.133_136dup p.(Tyr46∗) | nonsense | novel | – | 1 | Lalikher |
| LEPR | c.2114G>A (p.W705∗) | nonsense | Saeed et al.16 | – | 1 | Dogar |
| LEPR | c.489T>A (p.Y163∗) | nonsense | novel | – | 1 | Barfizai |
| LEPR | c.1810T>A (p.C604S) | missense | Saeed et al.16 | 0.609 (Dam) | 1 | Gujar |
| LEPR | c.2627C>T (p.P876L) | missense | Saeed et al.16 | 0.647 (Dam) | 1 | Mughal |
| LEPR | c.40G>A (p.E14K) | missense | Saeed et al.16 | 0.116 (Ben)c | 1 | Rehmani |
| LEPR | c.2153A>G (p.N718S) | missense | Saeed et al.16 | 0.665 (Dam) | 1 | Jutt |
| LEPR | c.2899_2900insAT(p.A967Dfs∗7) | frameshift | Saeed et al.16 | – | 1 | Jutt |
| LEPR | c.3268_3269del (p.S1090Wfs∗6) | frameshift | Bhatt et al.20 | – | 1 | Arain |
| LEPR | c.1738delG(p.E580Kfs∗37) | frameshift | Saeed et al.16 | – | 1 | Arain |
| LEPR | c.2875T>A (p.R959∗) and c.2872G>A (p.E958K) | compound heterozygous | Saeed et al.16 | – | 1 | Gujar |
| LEPR | ∼44 kb homozygous deletion including exons 3–20 of LEPR | CNV | Saeed et al.16 | – | 1 | Gujar |
| LEPR | ∼61 kb homozygous deletion including exons 3–6 of LEPR | CNV | Saeed et al.8 | – | 1 | Rajput |
| LEPR | 52 kb homozygous deletion | CNV | Saeed et al.16 | – | 1 | Rajput |
| MC4R | c.633_636delCTAT (p.Y212Sfs∗5) | frameshift | Saeed et al.16 | – | 1 | Khokhar |
| MC4R | c.47G>A (p.W16∗) | nonsense | Marti et al.21 | – | 3 | Jutt, Rajput (n = 2) |
| MC4R | c.63_64del (p.Y21∗) | nonsense | Saeed et al.16 | – | 2 | Arain (n = 2) |
| MC4R | c.601_612 del TTCTTCACCATG (p.F201_M204del) | in-frame deletion | Saeed et al.16 | – | 1 | Rehmani |
| MC4R | c.206T>C (p.I69T) | missense | Tan et al.22 | 0.592 (Dam) | 1 | Jutt |
| MC4R | c.482 T>C (p.M161T) | missense | Tan et al.22 | 0.488 (Uncer) | 3 | Pathan (n = 2), Memon |
| MC4R | c.493C>T (p.R165W) | missense | Hinney et al.23 | 0.501 (Dam) | 4 | Arain (n = 2), Jutt Sayal, Lashari |
| MC4R | c.811T>C (p.C271R) | missense | Farooqi et al.24 | 0.844 (Dam) | 1 | Bhatti |
| MC4R | c.947 T>C (p.I316S) | missense | Yeo et al.25 | 0.442 (Uncer) | 2 | Rajput, Sheikh |
LEP: NM_000230.3; LEPR: NM_002303.6; MC4R: NM_005912.3. Dam, damaging; Uncer, uncertain; Ben, benign.
a
Not available.
b
Undetectable levels of leptin hormone.
c
Located at essential splice site.