Segregation analysis in families with Charcot-Marie-Tooth disease allows reclassification of putative disease causing mutations

Table 2 Class 3 sequence variants not reported in the HGMDp database or other sources at the time of identification, and secondary classification after family studies

Gene	Family	Mutation		N tested total	N affected tested^†		N healthy tested^†		Primary classifi-cation^$	Secondary classifi-cation^£
Gene	Family	cDNA	Protein	N tested total	Pos	Neg	Pos	Neg	Primary classifi-cation^$	Secondary classifi-cation^£
MFN2	1^*	c.250 A > G	p.Lys84Glu	2	0	0	0	2^‡	3	3
	2	c.1709 A > G	p.Asn570Ser	4	1	0	2	1	3	2^¶
	3^*	c.2146_2148 dup	p.Ala716dup	3	1	0	0	2^‡	3	4
	4^*	c.692C > T	p.Ser231Phe	2	0	0	0	2^‡	3	4
MPZ	1^*	c.410 G > A	p.Gly137Asp	3	3	0	0	0	3	3
	2	c.103 G > A	p.Asp35Asn	3	2^€	0	0	1	3	4
	3^*	c.368 G > T	p.Gly123Val	5	2	0	0	3	3	3
NEFL	1^*	c.1027_1029del	p.Asp343del	1	1	0	0	0	3	3

^†In addition to index.
^$Primary classification of genetic variants in the index patient in accordance with the recommendations from the IARC Unclassified Genetic Variants Working Group; 4 = likely disease causing, 3 = uncertain, 2 = likely not disease causing [18].
^£Secondary classification of genetic variants after extended family investigations.
^*Sequence variants reported in a previous work [9].
^‡Parents negative, de novo mutation in the first following generation. MFN2 family 1; ongoing investigation, MFN2 family 3 and 4; mutation not found in 200 control chromosomes. Paternity was genetically verified.
^¶This variant was later reported with a possible association to dHMN in a single Norwegian patient [24].
^€One affected carrier remotely related to an index patient identified in 2012; not included in the total material.

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