Table 1.

Molecular genetic testing (MGT) results for patients shown to harbor LSD-causing pathogenic variants. Whenever clinical and/or biochemical data were available, that information was also included.

Patient	Molecular Diagnosis (#MIM)	Gene (RefSeq)	cDNA	Protein	Variant Type	In Silico Predictors #	Reference	Clinical Data (When Available)/Clinical Suspicion	Biochemical Phenotype	Origin
P1	Gaucher type I (#230800)	GBA NM_001005741.2	c. 1448T>C/c. 1448T>C	p.Leu483Pro/p.Leu483Pro	Missense	Pathogenic	[15]	At nine months: mild hepatomegaly; exuberant splenomegaly; feeding difficulties and dysphagia; bilateral convergent strabismus; marked axial hypotonia; poor facial mimic; global psychomotor development delay; cardiomegaly with dilatation of the left cavities; interstitial lung disease with multiple recurrent infections including aspiration pneumonia; three cardiac arrest events. Cerebral MRI showed supratentorial periventricular white matter alterations of tegmentum pontis and dentate nucleus, all aspects which are compatible with central nervous involvement in the context of Gaucher disease	Low GCase levels in skin fibroblasts	Cape Verdean
P2	Fabry disease (#301500)	GLA NM_000169	c.859T>C	p.Trp287Arg	Missense	Pathogenic	Novel	Fabry disease	-	Tunisian
P3	Pycnodysostosis (265800)	CTSK NM_000396.3	c.436G>C/c.436G>C	p.Gly146Arg/p.Gly146Arg	Missense	Pathogenic	[16]	Pyknodysostosis	-	Tunisian
P4	Mucolipidosis type II (#252500)	GNPTAB NM_024312.4	c.571G>A/c.571G>A	p.Val191Ile/p.Val191Ile	Missense	Mostly pathogenic	[17]	Mucolipidosis type II	-	Indian
P5	CLN7 (#610951)	MFSD8 NM_152778.2	c.1363G>C/c.1363G>C	p.Gly455Arg/p.Gly455Arg	Missense	Pathogenic	Novel	Neuronal ceroid lipofuscinosis	-	Tunisian
P6	Krabbe disease (#245200)	GALC NM_000153.3	c.613_617del/c.613_617del	p.Tyr205Ter/p.Tyr205Ter	Deletion	NA	Novel	Krabbe disease	-	Tunisian
P7	GM2A-gangliosidosis AB-variant (#272750)	GM2A NM_000405.4	c.312del/c.312del	p.Gly104Gly fsTer14/p.Gly104Gly fsTer14	Deletion	NA	Novel	Neurodegenerative LSD (not specified)	-	Tunisian
P10	MPSIIIB (#252920)	NAGLU NM_000263.3	c.934G>A/c.934G>A	p.Asp312Asn/p.Asp312Asn	Missense	Pathogenic	[18]	Mucopolysaccharidosis	-	Tunisian
P13	Alpha-mannosidosis (#248500)	MAN2B1 NM_000528.3	c.2402dup/c.2402dup	p.Ser802Gln fsTer21/p.Ser802Gln fsTer21	Duplication	Pathogenic	[19]	Alpha-mannosidosis	-	Tunisian

# In silico predictions for novel missense variants relied on the software wANNOVAR, which takes into account the results from a number of well-known algorithms on the phenotypic consequences of amino acid substitutions: FATHMM [20], SIFT [21], Mutation Taster [22], and PolyPhen 2 [23].