Variant profile of Brazilian patients with Sanfilippo syndrome type B

Oliveira Netto, Alice Brinckmann; Brusius-Facchin, Ana Carolina; Michelin‐Tirelli, Kristiane; Sebastião, Fernanda Medeiros; Trapp, Franciele Barbosa; Giugliani, Roberto; Baldo, Guilherme

doi:10.1590/1678-4685-GMB-2025-0174

person Alice Brinckmann Oliveira Netto

conducted the experiments · conducted software analysis · conducted formal analysis · data curation · wrote the manuscript · read and approved the final version of the manuscript

schoolUniversidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Genética e Biologia Molecular, Porto Alegre, RS, Brazil.

0000-0001-7888-8327

person Ana Carolina Brusius-Facchin

conducted the experiments · conducted software analysis · read and approved the final version of the manuscript

schoolInstituto de Genética para Todos, Porto Alegre, RS, Brazil.

person Kristiane Michelin‐Tirelli

conducted the experiments · read and approved the final version of the manuscript

schoolHospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre, RS, Brazil.

person Fernanda Medeiros Sebastião

conducted the experiments · read and approved the final version of the manuscript

schoolHospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre, RS, Brazil.

person Franciele Barbosa Trapp

conducted the experiments · read and approved the final version of the manuscript

schoolHospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Rede MPS Brasil, Porto Alegre, RS, Brazil.

person Roberto Giugliani

conceived the study · conducted formal analysis · resources · data curation · wrote the manuscript · read and approved the final version of the manuscript

schoolUniversidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Genética e Biologia Molecular, Porto Alegre, RS, Brazil.schoolHospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Rede MPS Brasil, Porto Alegre, RS, Brazil.schoolDASA Genômica, São Paulo, SP, Brazil.schoolInstituto Nacional de Genética Médica Populacional, Porto Alegre, RS, Brazil.

0000-0001-9655-3686

person Guilherme Baldo

conceived the study · conducted formal analysis · resources · data curation · wrote the manuscript · read and approved the final version of the manuscript

schoolUniversidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Genética e Biologia Molecular, Porto Alegre, RS, Brazil.schoolHospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Rede MPS Brasil, Porto Alegre, RS, Brazil.schoolUniversidade Federal do Rio Grande do Sul, Departamento de Fisiologia, Porto Alegre, RS, Brazil.

0000-0003-1598-5861

personSend correspondence to Roberto Giugliani, Instituto Nacional de Genética Médica Populacional, Rua Ramiro Barcelos, 2350, Sala 21506 (Centro de Pesquisa Clínica), 90035-903, Porto Alegre, RS, Brazil. E-mail:
rgiugliani@hcpa.edu.br.

Associate Editor:

Maria Luiza Petzl-Erler

Conflict of Interest

The authors declare that there is no conflict of interest that could be perceived as prejudicial to the impartiality of the reported research.

Patient	Allele 1	Allele 2	Enzyme¹	Quantification of GAGs [µg/mg creatinine]	GAGs Electrophoresis	Age at sample collection	Family data	State of birth
1	c.886delC p.(Leu296fs)	c.886delC p.(Leu296fs)	0.4 (P)	NP	HS	9	no information available	no information available
2	c.419A>G p.(Tyr140Cys)	-	0.21 (P)	28 mg/nmol (5.2-12)	no information available	8	no information available	no information available
3	c.503G>A p.(Trp168Ter)	c.700C>T p.(Arg234Cys)	0.2 (P)	NP	no information available	7	no information available	no information available
4	c.874G>A p.(Gly292Arg)	c.874G>A p.(Gly292Arg)	0.15 (P)	29 mg/nmol (5.7-13)	HS	8	no information available	no information available
5	c.1693C>T p.(Arg565Trp)	-	0.0 (P)	NP	HS	2	familial	ES
6	c.886delC p.(Leu296fs)	c.886delC p.(Leu296fs)	0.42 (P)	38 mg/nmol (5.7-13)	HS	9	no information available	no information available
7	c.607C>T p.(Arg203Ter)	-	0.15 (P)	600 (67-124)	HS	5	consanguinity	CE
8	c.1229T>C p.(Phe410Ser)	c.1420T>G p.(Trp474Gly)	0.26 (P)	NP	NP	26	no information available	SP
9	c.1597C>T p.(Arg533Ter)	c.1693C>T p.(Arg565Trp)	0.1 (P)	760 (44-106)	HS	7	no information available	RJ
10	c.1693C>T p.(Arg565Trp)	c.1876C>T p.(Arg626Ter)	0.8 (P)	NP	NP	6	no information available	RJ
11	c.419A>G p.(Tyr140Cys)	c.1927C>T p.(Arg643Cys)	0.30 (P)	164 (67-124)	HS	7	no information available	RS
12	c.1694G>A p.(Arg565Gln)	c.1694G>A p.(Arg565Gln)	0.0 (DBS)	230 (13-59)	HS	12	familial	CE
13	c.1694G>A p.(Arg565Gln)	c.1694G>A p.(Arg565Gln)	0.0 (DBS)	NP	HS	12	familial	CE
14	c.886delC p.(Leu296fs)	-	0.15 (L)	380 (79-256)	HS	2	no information available	no information available
15	c.1558C>T p.(Arg520Trp)	c.1558C>T p.(Arg520Trp)	0.2 (L)	1,954 (26-97)	no excretion	14	sporadic	MG
16	c.419A>G p.(Tyr140Cys)	c.2021G>A p.(Arg674His)	0.02 (L)	266 (53-115)	HS	6	sporadic	SP
17	c.700C>T p.(Arg234Cys)	c.700C>T p.(Arg234Cys)	0.0 (L)	505 (79-256)	HS	2	consanguinity	BA
18	c.607C>T p.(Arg203Ter)	c.607C>T p.(Arg203Ter)	0.5 (L)	176 (26-97)	HS	4	sporadic	CE
19	c.607C>T p.(Arg203Ter)	c.2186_2188delAAG p.(Lys728del)	0.21 (L)	251 (53-115)	HS	6	sporadic	AC
20	c.1597C>T p.(Arg533Ter)	c.1597C>T p.(Arg533Ter)	0.13 (L)	391 (67-124)	HS	4	consanguinity	RJ
21	c.886delC p.(Leu296fs)	c.886delC p.(Leu296fs)	0.05 (L)	655 (67-124)	HS	3	consanguinity	RJ
22	c.700C>T p.(Arg234Cys)	c.700C>T p.(Arg234Cys)	0.1 (P)	170 (26-97)	HS	9	consanguinity	BA
23	c.1793T>C p.(Leu598Pro)	c.235G>C p.(Gly79Arg)	0.5 (L)	439 (67-124)	HS	4	no information available	DF
24	c.192del p.(Tyr65fs)	-	0.5 (L)	361 (67-124)	HS	5	consanguinity	SP
25	c.1318G>C p.(Gly440Arg)	c.1834A>G p.(Ser612Gly)	0.19 (L)	77 (13-45)	HS	22	sporadic	SP
26	c.886delC p.(Leu296fs)	c.886delC p.(Leu296fs)	0.25 (P)	181 (44-106)	HS	8	sporadic	SC
27	c.1336G>A p.(Glu446Lys)	c.1336G>A p.(Glu446Lys)	2.6 (L)	164 (44-106)	DS + HS	8	consanguinity	DF

Location	Nucleotide change	Effect on protein	Alleles	Reference
Missense			29
exon 1	c.235G>C	p.Gly79Arg	1	this report
exon 2	c.419A>G	p.Tyr140Cys	3	Zhao et al., 1998
exon 4	c.700C>T	p.Arg234Cys	5	Beesley et al., 1998
exon 5	c.874G>A	p.Gly292Arg	2	Bunge et al., 1999
exon 6	c.1229T>C	p.Phe410Ser	1	Weber et al., 1999
exon 6	c.1318G>C	p.Gly440Arg	1	Montenegro et al., 2021
exon 6	c.1336G>A	p.Glu446Lys	2	Beesley et al., 2004
exon 6	c.1420T>G	p.Trp474Gly	1	Coll et al., 2001
exon 6	c.1558C>T	p.Arg520Trp	2	Tessitore et al., 2000
exon 6	c.1693C>T	p.Arg565Trp	3	Weber et al., 1999
exon 6	c.1694G>A	p.Arg565Gln	4	Bunge et al., 1999
exon 6	c.1793T>C	p.Leu598Pro	1	this report
exon 6	c.1834A>G	p.Ser612Gly	1	Zhao et al., 1998
exon 6	c.1927C>T	p.Arg643Cys	1	Weber et al., 1999
exon 6	c.2021G>A	p.Arg674His	1	Zhao et al., 1996
Nonsense			9
exon 2	c.503G>A	p.Trp168Ter	1	Coll et al., 2001
exon 3	c.607C>T	p.Arg203Ter	4	Schmidtchen et al., 1998
exon 6	c.1597C>T	p.Arg533Ter	3	Mangas et al., 2008
exon 6	c.1876C>T	p.Arg626Ter	1	Zhao et al., 1996
Small deletions and duplications			11
exon 1	c.192del	p.Tyr65fs	1	Beesley et al., 1998
exon 6	c.886delC	p.Leu296fs	9	Montenegro et al., 2022
exon 6	c.2186_2188delAAG	p.Lys728del	1	Pollard et al., 2013
Total			49

Coding sequence	Protein sequence	ACMG Classification	ACMG criteria	gnomAD frequency¹	SIFT²	PolyPhen³	Mutation Taster⁴
c.235G>C	p.(Gly79Arg)	VUS	PM1, PP3	not reported	damaging	0.992	deleterious
c.1793T>C	p.(Leu598Pro)	VUS	PM2, PP3	0.0000006217	damaging	0.990	deleterious

[TFN1] L: Leukocytes; P: Plasma; DBS: Dried Blood Spot; -: not found; NP: not performed; HS: Heparan Sulfate; DS: Dermatan Sulfate.

[TFN2] ¹Enzyme reference values: DBS (0.96-5.80 nmol/h/ml); L (10-34 nmol/17h/mg protein); P (11-37 nmol/h/ml); (GAGs reference value).

[TFN3] Reference sequences: NM_000263.3 (transcript) / NP_000254.2 (protein)