Novel homozygous mutations in Pakistani families with Charcot–Marie–Tooth disease

BMC Medical Genomics

Table 2 Homozygous mutations and clinical phenotypes in five Pakistani CMT patients

Family ID	Gene	Mutation^a	Type	Onset age (year)	Other symptom	Allele frequency		GERP	In silico prediction^b				Note
Family ID	Gene	Mutation^a	Type	Onset age (year)	Other symptom	1000G	gnomAD	GERP	PP2	MU	PRO	Fath	Note
PaC2	SH3TC2	c.2599C > T;p.Q867*	CMT4C	3	Scoliosis	UR	UR	2.17	–	–	–	–	P
PaC3	SH3TC2	c.3650G > A;p.G1217D	CMT4C	3	Scoliosis, short stature	UR	1.6E−5	6.17	1.00*	0.10	− 5.79*	− 2.66*	P
PaC4	HK1	c.19C > T;p.R7*	CMT4G	1		UR	2.0E−5	1.13	–	–	–	–	P
PaC6	REEP1	c.247delG;p.G83Afs*44	SMARD/dHMN5B	< 1		UR	UR	5.33	–	–	–	–	LP
PaC14	MFN2	c.334G > A;p.V112M	CMT2A2B	5	Vocal cord hoarseness	UR	1.6E−5	4.70	1.00*	0.32	− 2.76*	− 3.86*	P

1000G: 1000 Genomes Project, CMT: Charcot–Marie–Tooth disease, GERP: genomic evolutionary rate profiling score, gnomAD: Genome Aggregation Database, LP: likely pathogenic, P: pathogenic, LP: likely pathogenic, UR: unreported
^aReference DNA and protein sequences: SH3TC2: NM_024577.4 and NP_078853.2, HK1: NM_033498.3 and NP_277033.1, REEP1: NM_022912.3 and NP_075063.1, MFN2: NM_014874.3 and NP_055689.1
^bScores of PolyPhen-2 (PP2) ~ 1, MUpro (MU) < 0, PROVEAN (PRO) < − 2.5, and Fathmm (Fath) < − 1.5 indicate pathogenic prediction (*denotes a pathogenic prediction)

ISSN: 1755-8794