Table 1.

Summary of Molecular Genetic Testing Used in MCPH-SCKS Spectrum Disorders

Gene 1
(Locus Name)		Proportion of the Phenotype Attributed to Mutation of This GeneTest MethodVariants Detected 3
MCPH 2SCKS
MCPH1
(MCPH1)		<10%0%Sequence analysis 4Sequence variants
Deletion/duplication analysis 5Exon or whole-gene deletions or duplications
Targeted analysis for pathogenic variants 6 p.Ser25Ter
WDR62
(MCPH2)		<10%0%Sequence analysis 4Sequence variants
Deletion/duplication analysis 5Exon or whole-gene deletions or duplications; none reported 7
CDK5RAP2
(MCPH3)		<5%0%Sequence analysis 4Sequence variants
Deletion/duplication analysis 5Exon or whole-gene deletions or duplications; none reported 7
KNL1
(MCPH4)		<5%0%Sequence analysis 4Sequence variants
ASPM
(MCPH5)		25%-50%0%Sequence analysis 4Sequence variants
Deletion/duplication analysis 5Exon or whole-gene deletions 6
CENPJ
(MCPH6/ SCKL4)		<5%1 family 8Sequence analysis 4Sequence variants
Deletion/duplication analysis 5Exon or whole-gene deletions or duplications; none reported 7
STIL
(MCPH7)		<5%0%Sequence analysis 4Sequence variants
Deletion/duplication analysis 5Exon or whole-gene deletions or duplications; none reported 7
CEP135 (MCPH8)<5%2 individuals 9Sequence analysis 4Sequence variants
CEP152 (MCPH9/ SCKL5)<5%Majority of SCKSSequence analysis 4Sequence variants
Deletion/duplication analysis 5Exon or whole-gene deletions; none reported 5
PHC1
(MCPH11)		1 family with intermediate phenotype 10NANA
CDK6 (MCPH12)1 family 11NANA
ATR
(SCKL1)		0%4 families 12Sequence analysis 4Sequence variants
Deletion/duplication analysis 5Exon or whole-gene deletions or duplications; none reported 7
Targeted analysis for pathogenic variants 6IVS9-57A>G
RBBP8
(SCKL2)		0%1 family 13Sequence analysis 4Sequence variants
Deletion/duplication analysis 5Exon or whole-gene deletions or duplications; none reported 7
CEP63
(SCKL6)		0%1 family 14 with intermediate phenotypeNANA
NIN
(SCKL7)		0%1 family 15NANA
ATRIP 0%1 family 15NANA
1.
2.

For the MCPH phenotype, few studies have addressed the relative importance of each locus or included all known genes. See Table 3.

3.

See Molecular Genetics for information on allelic variants.

4.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

5.

Testing that identifies exon or whole-gene deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.

6.

Targeted pathogenic variants may vary by laboratory.

7.

No exon deletions or duplications have been reported to date. (Note: By definition, deletion/duplication analysis identifies rearrangements that are not identifiable by sequence analysis of genomic DNA.)

8.
9.
10.
11.
12.
13.
14.
15.

From: Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

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